Molecular FroNtiers · 2019. 7. 29. · ! 3!...

Nobel Workshop

&Molecular FroNtiers

syMposiuM

An Amazing Week at ChalmersMay 4th-8th 2015RunAn Conference Hall, Chalmers University of TechnologyChalmersplatsen 1, Gothenburg, Sweden

Nobel Workshop & Molecular Frontiers Symposium organized by:

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Welcome!(

The!Nobel!Workshop!and!Molecular!Frontiers!Symposium!in!Gothenburg!are!spanning!over!

widely!distant!horizons!of!the!molecular!paradigm.!From!addressing!intriguing!questions!of!

life! itself,! how! it! once! began! and! how! molecules! like! cogwheels! work! together! in! the!

complex! machinery! of! the! cell! E! to! various! practical! applications! of! molecules! in! novel!

materials!and!in!energy!research;!from!how!biology!is!exploiting!its!molecules!for!driving!the!

various! processes! of! life,! to! how! insight! into! the! fundamentals! of! photophysics! and!

photochemistry!of!molecules!may!give!us!clues!about!solar!energy!and!tools!by!which!we!

may!tame!it!for!the!benefit!of!all!of!us,!and!our!environment.!!

!

! Science!is!sometimes!artificially!divided!into!“fundamental”!and!”applied”!but!these!

terms!are!irrelevant!because!research!is!judged!to!be!groundbreaking!by!the!consequences!

it!may!have.!Any!groundbreaking! fundamental! result!has! sooner!or! later! consequences! in!

applications,!and!the!limits!are!often!only!drawn!by!our!imagination.!!

!

! Science!is!very!much!a!matter!of!communication:!we!not!only!learn!from!each!other!

(facts,!ideas!and!concepts),!we!also!need!interactions!for!inspiration!and!as!testing!ground!

for!our!ideas.!A!successful!scientific!communication!(publication!or!lecture)!always!requires!

a!pedagogically!delivered!message.!That!an!author!understands!what!he/she!is!doing!is!not!

a! guarantee! for! explaining! well! (although! it! often! helps!).! The! Molecular! Frontiers!

Symposium,!for!highEschool!pupils,!presents!a!special!challenge!to!the!speakers!for!making!

themselves! understood.! However,! I! would! say! the! difference! is! not! that! big! between!

speaking! to! your! peers! or! to! less! scientifically! trained! mind.! Common! to! all! scientific!

questions! is! that! they! need! to! be! broken! down! into! logical! elements:! a! hypothesis! is!

generally!tested!by!a!chain!of!arguments!and!the!total!strength!of!the!chain!is!always!limited!

by! its!weakest! link.!While!an!experienced! scientist! is! sometimes!blind! to!where! the!weak!

links!are,!a!young!and!unbiased!mind!sometimes!asks!the!really!good!questions.!This! is!an!

ability! that! we! will! recognize! by! The! Inquiry! Prize! –! a! unique! worldEwide! competition!

created!by!the!Molecular!Frontiers!Foundation,!where!the!prize!is!given!for!asking!a!really!good!question,!not!for!knowing!the!answer.!The!Inquiry!Prize!Jury!is!composed!of!members!

of!the!Scientific!Advisory!Board!of!the!Molecular!Frontiers!Foundation!and!they!will!award!

the!prizes!to!5!girls!and!5!boys.!!!

!

! A!hallmark!of!this!Amazing!Week!is!diversity:!we!shall!enjoy!the!lectures,!ideas!and!company!of! front! figures! from!a! range!of!different! fields.!Diversity! is!a! challenge,!but! the!

molecules-and-frontiers- in-molecular-sciences!are!the!common!denominator!of!this!week.!

This!is!a!great!opportunity!to!get!exposed!to!new!facts!and!new!ideas!and!be!inspired!!!

!

It!is!my!hope!that!all!of!you,!young!as!well!as!less!young,!will!enjoy!the!exciting!days!during!

this!week,!and!get!inspired!E!maybe!so!much!so!that!you!will!also!decide!to!devote!yourself!

to!science.!

!

Bengt!Nordén!

Professor,of,Physical,Chemistry,at,Chalmers,University,of,Technology,Founding,Chairman,of,the,Molecular,Frontiers,Foundation,

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!Nobel!Workshop!!

DAY!1!Organized!by!The!Royal)Swedish)Academy)of)Sciences!!

and!the!Chalmers!Life)Science)Engineering!Area!of!Advance!!!

Date:!! !!!!!!!!!!!!!!Monday!May!4th,!2015!Topic:!! ! MOLECULES!IN!LIFE!SCIENCE!RESEARCH!

! ! Chairs:!!! Prof.!Jens!Nielsen!and!Prof.!Andrew!Ewing!Venue:!!! RunAn!Conference!Hall,!Chalmers!University!of!Technology,!!

Chalmersplatsen!1,!SEL412!58!Göteborg,!Sweden!!

08:35L08:40! Welcome)note:"Prof"Karin"Markides,"Chalmers"President!

08:40L08:45! Opening)note:"Prof"Jens"Nielsen,"Director"of"Life"Science"Engineering"!

08:45L09:25! Prof!DAVID!LILLEY,!University!of!Dundee,!United!Kingdom!

How"does"RNA"act"like"an"enzyme!

09:25L10:05! Prof!PETER!von!HIPPEL,!University!of!Oregon,!United!States!

Mapping"structural"and"dynamic"interactions"of"regulatory"proteins"with"DNA"at"single"

nucleotide"resolution!

10.05L10:35! Coffee)break!

10:35L11:15! Nobel!Laureate!ADA!YONATH,!Weizmann!Institute!of!Science,!Israel!

SpeciesFspecific"antibiotics"and"the"microbiome"

11:15L11:55!! Prof!YAHLI!LORCH,!Stanford!University,!United!States!

Chromatin"remodeling!

11:55L12:55! Lunch)break!

12:55L13:35! Nobel!Laureate!ARIEH!WARSHEL,!University!of!Southern!California,!United!States!Evaluating"

and"using"free"energy"landscapes"for"biological"functions!!

13:35L14:15! Nobel!Laureate!MICHAEL!LEVITT,!Stanford!University,!United!States!

Solving"Large"&"Difficult"Structures"with"Less"Experimental"Data!!

14:15L14:55! Prof.!DINA!PETRANOVIC,!Chalmers!University!of!Technology,!Sweden!!

Yeast"as"a"model"for"human"diseases!

14:55L15:25! Coffee)break)

15:25L16:05!!! Prof!RICHARD!LERNER,!The!Scripps!Research!Institute,!United!States!!

Selecting"Antibodies"from"Combinatorial"Libraries"for"the"Treatment"of"Cancer!!

16:05L16:45! Prof!ANDREW!McCAMMON,!University!of!California,!San!Diego,!United!States!Molecular"

Dynamics"and"Drug"discovery!

16:45L18:00! Panel)discussion:)Opportunities)and)Challenges)in)Life)Science)Research!!

(Moderators:!Jens!Nielsen!and!Andrew!Ewing)!

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!Nobel!Workshop!!

DAY!2!Organized!by!The)Royal)Swedish)Academy)of)Sciences!!

and!the!Chalmers!Energy)and)Nanoscience)and)Nanotechnology!Areas!of!Advance!!!

Date:! !!!!!!!!!!!!!!Tuesday!May!5th,!2015!Topic:! ! MOLECULES!IN!NANO!AND!ENERGY!RESEARCH!

! ! Chairs:! ! Prof.!Bo!Albinsson!and!Dr.!Anders!Ådahl!Venue:!!! RunAn!Conference!Hall,!Chalmers!University!of!Technology,!!


08:25L08:30! Opening)note:"Prof"Bo"Albinsson,"Director"of"Nanoscience"and"Nanotechnology"and"Dr."

Anders"Ådahl,"Director"of"Energy"!

08:30L09:10! Prof!HARRY!GRAY,!California!Institute!of!Technology,!United!States:!The"Currents"of"Life:"

Electron"Flow"through"Proteins"

09:10L09:50! Nobel!Laureate!ROGER!KORNBERG,!Stanford!University,!United!States!

Metal"nanoparticles:""atomic"structures"and"applications"in"cryoFelectron"microscopy!

09:50L10:20! Coffee)break!

10:20L11.00! Prof!REIKO!KURODA,!University!of!Tokyo,!Japan!

A"twisting"story:"how"a"single"gene"twists"a"snail!

11:00L11:40! Prof!WAYNE!HENDRICKSON,!Columbia!University,!United!States!

Distinctions"and"Shared"Principles"in"Transmembrane"Ion"Channels""

11:40L12:20! Nobel!Laureate!KURT!WÜTHRICH,!The!!Scripps!!Research!!Institute,!!United!States!!!!

Sunset"of"the"NIH"Protein"Structure"Initiative"–"What"Next?"

12:20L13:20! Lunch)break!

13:20L14:00! Nobel!Laureate!JEANSMARIE!LEHN,!University!of!Strasbourg,!France!

Towards"adaptive"chemistry!

14:00L14:40! Nobel!Laureate!BARRY!SHARPLESS,!The!Scripps!Research!Institute,!United!States!Exploring"

the"Sulfate"World"

14:40L15:10! Coffee)break)!

15:10L15:50! Prof!JOSEF!MICHL,!University!of!Colorado!at!Boulder,!United!States,!and!Institute!of!Organic!

Chemistry!and!Biochemistry!ASCR,!Prague,!Czech!Republic!

Unconventional"solar"energy"–"singlet"fission!

15:50L16:30! Prof!Sir!JOHN!MEURIG!THOMAS,!University!of!Cambridge,!United!Kingdom!

Tomorrow's"Catalysts:"Actual"and"Desired!

16:30L18:00!! Panel)discussion:)Opportunities)and)Challenges)in)Nanotechnology)and)Energy!Research)

(Moderators:!Bo!Albinsson!and!Anders!Ådahl)! !

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!Nobel!Workshop!!

DAY!3!Organized!by!The)Royal)Swedish)Academy)of)Sciences!!and!the!Chalmers!Materials)Sciences!Area!of!Advance!!

!Date:! !!!!!!!!!!!!!!Wednesday!May!6th,!2015!Topic:! ! MOLECULES!IN!MATERIALS!RESEARCH!Chairs:!!! Prof.!Aleksandar!Matic!and!Prof.!Fredrik!Höök!Venue:!!! RunAn!Conference!Hall,!Chalmers!University!of!Technology,!!


08:25L08:30! Opening)note:"Prof"Aleksandar"Matic,"Director"Materials"Science"!

08:30L09:10! Nobel!Laureate!STEFAN!HELL,!University!of!Göttingen,!Germany!

Nanoscopy"with"focused"light!

09:10L09:50! Nobel!Laureate!WILLIAM!MOERNER,!Stanford!University,!United!States!

Single"molecule"spectroscopy!


10:20L11:00! Prof!ROBERT!LANGER,!Massachusetts!Institute!of!Technology,!United!States!!

Advances"in"biomaterials"and"drug"delivery!

11:00L11:40! Prof!TOM!BROWN,!University!of!Oxford,!United!Kingdom!

Chemical"synthesis"of"DNA"–"RealFworld"applications!

11:40L12:20! Nobel!Laureate!ANDREW!FIRE,!Stanford!University,!United!States!

Taming"opportunistic"RNAs!

12:20L13:20! Lunch)break)!

13:20L14:00! Prof!JAMES!BARBER,!Imperial!College!London,!United!Kingdom!

From"natural"to"artificial"photosynthesis"for"renewable"fuels!

14:00L14:40! Prof!PAUL!ALIVISATOS,!University!of!California!Berkeley,!United!States!

Nanoscience"and"the"Future"of"the"Carbon"Cycle!

14:40L15:20!!! Prof!TOSHIO!YANAGIDA,!Osaka!University,!Japan!

Role"of"fluctuations"for"driving"bioFmolecular"machines"!


15:50L16:30! Dr!RICHARD!HENDERSON,!MRC!LMB,!Cambridge,!United!Kingdom!

! Structure"of"membrane"proteins"involved"in"signal"transduction"

16:30L18:00! Panel)discussion:)Opportunities)and)Challenges)in)Materials!Research))

(Moderators:!Aleksandar!Matic!and!Fredrik!Höök)!!

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!Molecular!Frontiers!Symposium!!


and!Molecular)Frontiers)Foundation!!

Date:! !!!!!!!!!!!!!!Thursday!May!7th,!2015!Topic:! ! FRONTIERS!IN!MOLECULAR!SCIENCES!Chairs:!!! Prof!Bengt!Norden!and!Prof!Richard!Zare!Venue:!!! RunAn!Conference!Hall,!Chalmers!University!of!Technology,!!


08:40L08:45! Welcome!note:!Prof!Bengt!Nordén,!Chair!of!the!MFF!

08:45L09:25! Nobel!Laureate!AHMED!ZEWAIL,!California!Institute!of!Technology,!United!States!

Seeing"with"Electrons"in"Four"Dimensions"

09:25L10:05! Prof!GEORGE!WHITESIDES,!Harvard!University,!United!States!

Origin"of"life,"and"cellFsurface"biochemistry!


10:35L11:15! Nobel!Laureate!ARVID!CARLSSON,!with!Prof!ELIAS!ERIKSSON,!Gothenburg!University,!

Sweden:!!

Small"molecules"for"signaling"in"the"brain!

11:15L11:55! Prof!JACQUELINE!BARTON,!California!Institute!of!Technology,!United!States!

DNA"mediated"signaling!!

11:55L12:55! Lunch)break!!

12:55L13:35! Prof!DAVID!BUCKINGHAM,!University!of!Cambridge,!United!Kingdom"

Chiral"discrimination"in"NMR"spectroscopy!

13:35L14:15! Prof!PETER!DERVAN,!California!Institute!of!Technology,!United!States!

Transcription"Factor"Antagonists:"From"Discovery"to"Oncology!

14:15L14:55!! Prof!SUSAN!LINDQUIST,!Massachusetts!Institute!of!Technology,!United!States!Lamarck"was"

right:"better"living"through"chemistry.!

14:55L15:25!! Coffee)break!

15:25L16:40! Youth!Forum!(Moderators!Prof.!Magdalena!Eriksson!and!Dr!Per!Thoren)!

16:40L17:00! Let’s!Talk!about!Science!(Dr!Per!Thoren!and!Dr!Elizabeth!Ball)!!

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!Molecular!Frontiers!Symposium!!


and!Molecular)Frontiers)Foundation!!

Date:! !!!!!!!!!!!!!!Friday!May!8th,!2015!Topic:! ! FRONTIERS!IN!MOLECULAR!SCIENCES!Chairs:!!! Prof!Bengt!Norden!and!Prof!Dina!Petranovic!!Venue:!!! RunAn!Conference!Hall,!Chalmers!University!of!Technology,!!


08:30L09:10! Prof!FRANCES!ARNOLD,!California!Institute!of!Technology,!United!States!

Evolution"to"expand"the"enzyme"universe!!

09:10L09:50! Prof!CHRIS!DOBSON,!University!of!Cambridge,!United!Kingdom!

Mechanisms"of"misfolding"proteins)!


10:20L11:00! Prof!RICHARD!ZARE,!Stanford!University,!United!States!

Understanding"chemical"reactions"at"the"molecular"level)!

11:00L11:40! Prof.!DINSHAW!PATEL,!Memorial!Sloan!Kettering!Cancer!Center,!United!States!

CuttingFedge"RNA"slicers!

11:40L12:40! Lunch!break!!

12:40L13:20! Prof.!WAH!CHIU,!Baylor!College!of!Medicine,!Houston,!USA!!

Electron"CryoFMicroscopy"of"Molecular"Machines"

13:20L14:00! Nobel!Laureate!SHUJI!NAKAMURA,!University!of!California!Santa!Barbara,!United!States:!

Invention"of"Blue"LED,"Laser"and"Solid"State"Light!

14:00L14:20! Coffee)break)!

14:20L15.30! Panel)discussion:)Science)and)engineering)in)and)outside)of)the)classroom)

(Moderators:!Bengt!Norden!and!Dina!Petranovic)!!

15:30L16:00! Presentation!of!the!Molecular!Frontiers!Inquiry!Prize!!

(Moderators!Dr!Per!Thoren!and!Deborah!Donnelly!McLay)!

16:00L16:15! Conclusion:!Prof.!BARBARA!CANNON,!President!of!the!Royal!Swedish!Academy!of!Sciences!

16:15L16:30! Closure:!Prof.!BENGT!NORDEN,!Founding!Chairman!of!the!Molecular!Frontiers!Foundation!!

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Organization*

Scientific*committee* *!Bengt! Nordén!Dina! Petranovic!Marcus! Wilhelmsson!Bo! Albinsson!Elin!! Esbjörner!Winters!Per! Lincoln!Fredrik! Westerlund!!Organizing*committee* *!Bengt! Nordén!Dina! Petranovic!Åsa! Rensfeldt!Francesco! Gatto!Gunilla! Saethe!Anna! Molander!Marcus! Wilhelmsson!Per! Thorén!Fredrik! Westerlund!Anna! Bergius!Lotta! Pettersson!*Other*volunteers**Martina! Butorac!Eugene! Fletcher!Karolina! Partheen!Ingela! Roos!*Administration!och!service/Kommunikation!och!marknad/Varumärkesprofilering!&!kanaler!office!in!Chalmers!University!of!Technology!!

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Abstracts*Speakers*..................................................................................................................................*12!

Professor!Paul!Alivisatos!.............................................................................................................................!12!Professor!Frances!Arnold!............................................................................................................................!14!Professor!James!Barber!..............................................................................................................................!16!Professor!Jacqueline!Barton!.......................................................................................................................!18!Professor!Tom!Brown!.................................................................................................................................!20!Professor!David!Buckingham!......................................................................................................................!22!Professor!Arvid!Carlsson!with!Elias!Eriksson!...............................................................................................!24!Professor!Wah!Chiu!....................................................................................................................................!26!Professor!Peter!Dervan!...............................................................................................................................!28!Professor!Chris!Dobson!...............................................................................................................................!30!Professor!Andrew!Fire!................................................................................................................................!32!Professor!Harry!Gray!...................................................................................................................................!34!Professor!Stefan!Hell!...................................................................................................................................!36!Professor!Richard!Henderson!.....................................................................................................................!38!Professor!Wayne!Hendrickson!....................................................................................................................!40!Professor!Roger!Kornberg!...........................................................................................................................!42!Professor!Reiko!Kuroda!...............................................................................................................................!44!Professor!Robert!Langer!.............................................................................................................................!46!Professor!Jean]Marie!Lehn!.........................................................................................................................!48!Professor!Richard!Lerner!.............................................................................................................................!50!Professor!Michael!Levitt!.............................................................................................................................!52!Professor!David!Lilley!..................................................................................................................................!54!Professor!Susan!Lindquist!...........................................................................................................................!56!Professor!Yahli!Lorch!...................................................................................................................................!58!Professor!Andrew!McCammon!...................................................................................................................!60!Professor!Josef!Michl!..................................................................................................................................!62!Professor!William!Moerner!.........................................................................................................................!64!Professor!Shuji!Nakamura!...........................................................................................................................!66!Professor!Dinshaw!Patel!.............................................................................................................................!68!Professor!Dina!Petranovic!...........................................................................................................................!70!Professor!Barry!Sharpless!...........................................................................................................................!72!Professor!Sir!John!Meurig!Thomas!.............................................................................................................!74!Professor!Peter!von!Hippel!.........................................................................................................................!76!Professor!Ariel!Warshel!..............................................................................................................................!78!Professor!George!Whitesides!......................................................................................................................!80!Professor!Kurt!Wüthrich!.............................................................................................................................!82!Professor!Toshio!Yanagida!..........................................................................................................................!84!Professor!Ada!Yonath!.................................................................................................................................!86!Professor!Richard!Zare!................................................................................................................................!88!Professor!Ahmed!Zewail!.............................................................................................................................!90!

*

Chairs*and*Moderators*............................................................................................................*92!Professor!Bo!Albinsson!...............................................................................................................................!92!Doctor!Elizabeth!Ball!...................................................................................................................................!93!Professor!Barbara!Cannon!..........................................................................................................................!94!Professor!Magdalena!Eriksson!....................................................................................................................!95!Professor!Andrew!Ewing!.............................................................................................................................!96!Professor!Fredrik!Höök!...............................................................................................................................!97!Professor!Karin!Markides!............................................................................................................................!98!Professor!Aleksandar!Matic!........................................................................................................................!99!Doctor!Deborah!Donnelly!McLay!..............................................................................................................!100!Professor!Jens!Nielsen!..............................................................................................................................!101!Professor!Bengt!Nordén!............................................................................................................................!102!Doctor!Per!Thoren!.....................................................................................................................................!103!Professor!Anders!Ådahl!.............................................................................................................................!104* *

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!!

13!

Nanocrystals*Are*A*Fundamental*Building*Block*Of*Nanoscience*And*Of*Nanotechnologies*For*A*Balanced*Carbon*Cycle*!Inorganic!nanocrystals!have!emerged!as!an! important!building!block!of!nanoscience.! ! It! is!possible!today!to!control!the!size,!shape,!connectivity,!and!topology!of!nanocrystals.!!These!tiny! crystals! exhibit! strongly! site! dependent! properties,! according! to! basic! scaling! laws! of!nanoscience.! ! This! predictable! control! over! properties! gives! scientists! the! ability! to!purposefully! design! new! materials! with! beneficial! applications! in! biological! imaging! and!renewable!energy.!!This!talk!will!emphasize!recent!work!in!which!nanocrystals!are!deployed!for!energy!storage!and!solar!energy!conversion!systems.!! !

"#!

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15!

The*Nature*of*Chemical*Innovation:*New*Enzymes*by*Evolution*

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How!does!an!inherently!conservative!process!like!evolution!create!a!new!enzyme?!We!want!to!understand!how!chemical!novelty!arises!so!that!we!can!guide!this!creative!process!in!the!laboratory.! Not! satisfied! with! nature’s! vast! catalytic! repertoire,! we! want! to! ‘breed’! new!enzymes!and!expand!the!range!of!genetically!encoded!chemistry.!!

!

I!will!describe!how!we!use!the!most!powerful!algorithm!for!biological!design,!evolution,!to!optimize! existing! enzymes! and! create! whole! new! ones.! Mimicking! nature’s! evolutionary!tricks!and!using!a! little!chemical! intuition,!we!can!engineer!enzymes!to!catalyze!important!reactions! not! known! in! nature.! ! With! synthetic! reagents! to! generate! new! reactive!intermediates!and!just!a!few!amino!acid!substitutions!to!tune!the!active!site,!a!cytochrome!P450! can! catalyze! a! variety! of! carbene! and! nitrene! transfer! reactions.! ! The!cyclopropanation,! N]H! insertion,! C]H! amination,! sulfimidation,! and! aziridination! reactions!now! demonstrated! are! all! well]known! in! chemical! catalysis! but! have! no! counterparts! in!nature.! ! The!new!enzymes! are! fully! genetically! encoded,! assemble! and! function! inside! of!cells,! and! can! be! optimized! for! different! substrates,! activities,! and! selectivities.! Using!nature’s! innovation! mechanisms,! we! can! now! marry! some! of! the! synthetic! chemists’!favorite!transformations!with!the!exquisite!selectivity!and!tunability!of!enzymes.!!! !

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16!

Professor*James*Barber*Imperial!College!London,!United!Kingdom!!James! Barber! graduated! in! Chemistry! from! the!University!of!Wales.!His!M.Sc.!and!Ph.D!in!Biophysics!were! awarded! by! the! University! of! East! Anglia.! He!joined!the!academic!staff!of!Imperial!College!London!(ICL)! in! 1968! where! he! is! now! a! Senior! Research!Fellow! and! Emeritus! Ernst! Chain! Professor! of!Biochemistry.!During!his!time!at!ICL!he!has!served!as!Dean!of!the!Royal!College!of!Science!and!for!10!years!was! Head! of! the! Biochemistry! Department.! Until!recently! he! was! a! Visiting! Professor! to! the!Politecnico!di!Torino!(Italy)!and!is!the!Cannon!Visiting!Professor! to! the! Nanyang! Technological! University!(Singapore).!!He!is!a!Fellow!of!the!Royal!Society!(FRS)!and!the!Royal!Society!of!Chemistry!(FRSC),!a!member!of!the!European!Academy!(Academia!Europaea)!and!a!Foreign!Member!of!the!Royal!Swedish!Academy!of!Sciences.!He!holds!honorary!doctorates!of!Stockholm!University!and!University!of!East!Anglia.!He!has!been!awarded! the! Flintoff!Medal! of! the! Royal! Society! of!Chemistry,! Italgas/Eni! Prize! for! Energy! and! the! Environment,! the! Biochemical! Society!Novartis!Medal!and!Prize!and!the!!Wheland!Medal!and!Prize!from!the!University!of!Chicago.!Recently!he!was!the!Lee!Kuan!Yew!Distinguished!Visitor!to!Singapore!and!gave!the!Sir!Ernst!Chain! Distinguished! Lecture! at! ICL.! Last! year! he! received! the! Interdisciplinary! Award! and!Medal!of!the!Royal!Society!of!Chemistry.**!His! research! focuses! on! the! molecular! processes! of! photosynthesis,! particularly! the!reactions!which!bring!about!the!splitting!of!water!to!oxygen!and!high!energy!electrons.!His!work! underpins! the! recent! upsurge! in! artificial! photosynthesis! research! to! replicate! this!reaction!for!generation!of!fuel!and!he!active!in!this!field.! !

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17!

From*Natural*To*Artificial*Photosynthesis*For*Renewable*Fuels*!

The!oxygen!in!our!atmosphere!is!derived!and!maintained!by!the!water!splitting!process!of!

photosynthesis.!The!enzyme!which!facilitates!this!reaction!and!therefore!underpins!virtually!

all! life! on! our! planet! is! known! as! Photosystem! II! (PSII).! It! is! a! multisubunit! enzyme!

embedded! in! the! lipid! environment! of! the! thylakoid! membranes! of! plants,! algae! and!

cyanobacteria.!

!

Powered!by!light,!this!enzyme!catalyses!the!chemically!and!thermodynamically!demanding!

reaction! of! water! splitting.! In! so! doing,! it! releases! dioxygen! into! the! atmosphere! and!

provides! the! reducing! equivalents! required! for! the! conversion! of! carbon! dioxide! into! the!

organic! molecules! of! life! and! is! the! origin! of! the! fossil! fuels.! During! the! past! years! fully!

refined!structures!of!a!700!kDa!!cyanobacterial!dimeric!PSII!complex!has!been!elucidated!by!

X]ray! crystallography! which! has! given! the! ! organisational! details! of! ! the! 19/20! subunits!

(16/17!intrinsic!and!3!extrinsic)! !which!make!up!each!monomer!and!!provided!information!

about!the!position!and!protein!environments!of!!the!cofactors!involved!in!the!absorption!of!

light,!charge!separation!and!water!splitting.!!In!the!case!of!the!latter,!a!cluster!of!three!Mn!

ions!and!a!Ca!ion!which!form!a!cubane!structure!with!bridging!oxygens!plus!a!forth!Mn!ion!

linked!by!oxo!bonds!to!the!cubane,!makes!up!the!heart!of!the!catalytic!site.!Surrounding!the!

metal!cluster!are!highly!conserved!amino!acid!side!chains,!of!which!7!form!direct!ligands!to!

the! metals.! The! structure! of! the! catalytic! site! has! provided! ! a! framework! to! develop! a!

mechanistic! scheme! for! the! water! ! splitting! reaction! leading! to! dioxygen! formation.!

Moreover!it!has!provided!a!platform!to!mimic!the!natural!enzyme!in!order!create!“artificial!

photosynthesis”! technology! to! capture! solar! energy! and! store! it! in! chemical! bonds.! Such!

solar! fuel! technology! could! play! a! significant! role! in! elevating! ! the! daunting! problem! of!

increasing! levels! !of!carbon!dioxide! ! in!the!atmosphere!due!to!fossil! fuel!combustion! !and!

the!associated!worry!about!!global!climate!change.! !

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Professor*Jacqueline*Barton*California!Institute!of!Technology,!United!States!

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Dr.! Jacqueline! K.! Barton! is! the! Arthur! and! Marian!Hanisch!Memorial!Professor!of!Chemistry!and!Chair!of!the!Division!of!Chemistry!and!Chemical!Engineering!at!the!California!Institute!of!Technology.!Barton!obtained!her!Ph.D.!at!Columbia!University.!!After!a!postdoctoral!fellowship!at!Bell!Laboratories!and!Yale!University,!she!joined!the!faculty!at!Hunter!College,!City!University!of!New! York.! ! In! 1983,! she! returned! to! Columbia!University,! becoming! an! associate! professor! of!chemistry! and! biological! sciences! in! 1985! and!professor! in!1986.! ! In! the! fall!of!1989,! she! joined! the!faculty! at! Caltech.! ! In! 2009,! she! began! her! term! as!Chair!of!the!Division.!!Professor!Barton!has!pioneered!the!application!of!transition!metal!complexes!to!probe!recognition! and! reactions! of! double! helical! DNA.! ! In!particular,! she! has! carried! out! studies! to! elucidate!electron! transfer! chemistry! mediated! by! the! DNA!double! helix.! This! chemistry! has! been! applied! in! the!development! of! DNA]based! electrochemical! sensors! and! explored! in! the! context! of! long!range!signaling!within!the!cell.!!

Through! this! research,! Barton! has! trained! more! than! 100! graduate! students! and!postdoctoral! students.! ! Barton! has! received! numerous! awards! for! this! research.! ! These!include! the! NSF! Waterman! Award,! the! American! Chemical! Society! (ACS)! Award! in! Pure!Chemistry,!a!MacArthur!Foundation!Fellowship!and,!most!recently!the!ACS!Priestley!Medal.!She! has! been! elected! to! the! American! Academy! of! Arts! and! Sciences,! the! American!Philosophical!Society,! the!National!Academy!of!Sciences,!and! the! Institute!of!Medicine.! In!2011,!Barton!received!the!2010!National!Medal!of!Science.! !

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DNANmediated*Signaling*!

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Many! experiments! have! now! shown! that! double! helical! DNA! can! serve! as! a! conduit! for!efficient!charge!transport!over!long!molecular!distances.!!We!have!seen,!for!example,!using!tethered! metal! complexes! as! photooxidants,! that! oxidative! damage! to! DNA! can! be!promoted! from! a! distance! as! a! DNA]mediated! redox! process.! Photophysical,!electrochemical! and! biochemical! experiments! have! been! conducted! to! characterize! this!chemistry.! This! chemistry! is! exquisitely! sensitive! to! perturbations! in! the! DNA! base! stack,!such! as! arise! with! base! mismatches,! lesions,! and! protein! binding.! We! have! now! been!exploring! how! this! chemistry! may! be! used! within! the! cell! for! long! range! signaling.!!Increasingly,! 4Fe]4S! clusters! are!being! found! in!DNA]binding!proteins! involved! in! genome!maintenance.! Studies! are! described! to! characterize! DNA–mediated! signaling! by! these!metalloproteins.!Experiments!indicate!that! long!range!DNA!charge!transport!can!provide!a!first! step! in! how! DNA! repair! proteins!may! localize! in! the! vicinity! of! lesions.! DNA! charge!transport,! in! carrying! out! redox! chemistry! at! a! distance,! offers! a! route! for! long! range!signaling!and!coordination!of!DNA!repair!and!DNA]processing!proteins!across!the!genome.!! !

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Professor*Tom*Brown*University!of!Oxford,!United!Kingdom !Tom! Brown! received! a! first! class! honours!degree! and! PhD! in! Chemistry! from! the!University! of! Bradford! then! carried! out!postdoctoral! research! at! Nottingham!University,! Oxford! University! and! Cambridge!University.!He!was! appointed! to! a! Lectureship!in!Biological!Chemistry!at!Edinburgh!University!where! he! was! promoted! to! Reader! then!Professor.! He! moved! to! Southampton!University! in! 1995!where! he!was! Professor! of!Chemical! Biology! until! 2013.! He! is! currently!Professor! of! Nucleic! Acid! Chemistry! at! Oxford!University!and!is!a!member!of!the!Departments!of! Chemistry! and! Oncology.! His! research!interests! centre! on!DNA! sequence! recognition!and! applications! of! oligonucleotide! chemistry!in!biology!and!medicine.!!!He!is!the!co]founder!of!three!Biotech!companies!(Oswel,!ATDBio!and!Primer!Design)!and!has!published!over!300!research!papers!and!patents.!He!has!received!several!awards!including!the! Royal! Society! of! Chemistry! Josef! Loschmidt! prize,! the! RSC! award! for! Nucleic! Acid!Chemistry,!the!RSC!prize!for!Interdisciplinary!Research!and!is!Chemistry!World!entrepreneur!of!the!year!for!2014.!Tom!is!a!Fellow!of!the!Royal!Society!of!Edinburgh!and!a!Fellow!of!the!Royal! Society! of! Chemistry.! He! is! currently! President! of! the! Chemistry! Biology! Interface!Division!of! the!Royal!Society!of!Chemistry!and!Editor! in!Chief!of! the!new!Royal!Society!of!Chemistry!Book!series!on!Chemical!Biology.! !

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21!

Chemical*Synthesis*Of*DNA*–*RealNWorld*Applications*!In!this!lecture!I!will!discuss!practical!applications!of!oligonucleotide!synthesis!and!focus!on!click! ligation,! a! chemical! process! that! utilizes! the! copper]catalyzed! azide]alkyne!cycloaddition! (CuAAC! reaction).! This! efficient! method! of! joining! together! DNA! and! RNA!strands! has! been! used! for! the! synthesis! of! cyclic! oligonucleotides,1]3! oligonucleotide!catenanes,2! very! stable! cyclic! mini]duplexes,1! duplexes! that! are! linked! across! the! major!groove,4! covalently! fixed! DNA! nanoconstructs5! and! large! RNA! constructs.6! _ENREF_1! The!method!produces!an!unnatural!DNA!backbone! linkage! that!can!be!varied!by!changing! the!structures! of! the! participating! alkyne! and! azide.7! Careful! design! produced!DNA!backbone!that! can! be! read! through! by! DNA8! and! RNA! polymerases9,! 10! and! is! biocompatible! in!bacterial!and!human!cells.11,!12!A!high]resolution!NMR!study!revealed!that!the!click!linkage!is!accommodated! in! a! B]DNA! helix! with! minor! distortion.13! This! methodology! has! recently!been! used! to! characterise! a! new! form! of! stretched! DNA.14! Copper]free! click! DNA! strand!ligation! and! crosslinking! can! also! be! carried! out! if! strained! cyclooctyne! analogues! are!used.15]17!This!method!is!potentially!valuable!for! in#vivo!applications!as! it!does!not!require!metal!ion!catalysis.!Recent!biotechnology18!and!nanotechnology19!developments!in!this!field!will!be!discussed.#!!1.! A.!H.!El]Sagheer,!R.!Kumar,!S.!Findlow,!J.!M.!Werner,!A.!N.!Lane!and!T.!Brown,!Chembiochem,!2008,!9,!50]52.!2.! R.!Kumar,!A.!H.!El]Sagheer,!J.!Tumpane,!P.!Lincoln,!L.!M.!Wilhelmsson!and!T.!Brown,!J.#Am.#Chem.#Soc.,!2007,!129,!6859]6864.!3.! A.!H.!El]Sagheer!and!T.!Brown,!Int.#J.#Peptide#Res.Therapeut.,!2008,!14,!367]372.!4.! P.!Kocalka,!A.!H.!El]Sagheer!and!T.!Brown,!Chembiochem,!2008,!9,!1280]1285.!5.! E.! P.! Lundberg,! A.! H.! El]Sagheer,! P.! Kocalka,! L.!M.!Wilhelmsson,! T.! Brown! and! B.! Norden,!Chem.#Commun.,!2010,!46,!3714]3716.!6.! A.!H.!El]Sagheer!and!T.!Brown,!Proc.#Natl.#Acad.#Sci.#U.#S.#A.,!2010,!107,!15329]15334.!7.! A.!H.!El]Sagheer!and!T.!Brown,!J.#Am.#Chem.#Soc.,!2009,!131,!3958]3964.!8.! A.!H.!El]Sagheer,!A.!P.!Sanzone,!R.!Gao,!A.!Tavassoli!and!T.!Brown,!Proc.#Natl.#Acad.#Sci.#U.#S.#A.,!2011,!108,!11338–11343.!9.! A.!H.!El]Sagheer!and!T.!Brown,!Chem.#Commun.,!2011,!47,!12057]12058.!10.! A.!H.!El]Sagheer!and!T.!Brown,!Chemical#Science,!2014,!5,!253]259.!11.! C.!N.!Birts,!A.!P.!Sanzone,!A.!H.!El]Sagheer,!J.!P.!Blaydes,!T.!Brown!and!A.!Tavassoli,!Angew.#Chem.#Int.#Edit.,!2014,!53,!2362]2365.!12.! A.! P.! Sanzone,! A.! H.! El]Sagheer,! T.! Brown! and! A.! Tavassoli,!Nucleic# Acids# Res.,! 2012,! 40,!10567]10575.!13.! A.! Dallmann,! A.! H.! El]Sagheer,! L.! Dehmel,! C.! Mügge,! C.! Griesinger,! N.! P.! Ernsting! and! T.!Brown,!Chemistry#B#A#European#Journal,!2011,!17,!14714]14717.!14.! N.! Bosaeus,! A.! H.! El]Sagheer,! T.! Brown,! S.! B.! Smith,! B.! Akerman,! C.! Bustamante! and! B.!Norden,!Proc.#Natl.#Acad.#Sci.#U.#S.#A.,!2012,!109,!15179]15184.!15.! M.! Shelbourne,! X.! Chen,! T.! Brown!and!A.!H.! El]Sagheer,!Chem.#Commun.,! 2011,! 47,! 6257]6259.!16.! M.!Shelbourne,!A.!H.!El]Sagheer!and!T.!Brown,!Chem.#Commun.,!2012,!48,!11184]11186.!17.! J.!Q.!Qiu,!A.!H.!El]Sagheer!and!T.!Brown,!Chem.#Commun.,!2013,!49,!6959]6961.!18.! N.! Bosaeus,! A.! H.! El]Sagheer,! T.! Brown,! S.! B.! Smith,! B.! Akerman,! C.! Bustamante! and! B.!Norden,!Proc.#Natl.#Acad.#Sci.#U.#S.#A.,!2012,!109,!15179]15184.!19.! S.!R.!Gerrard,!C.!Hardiman,!M.! Shelbourne,! I.!Nandhakumar,!B.!Norden!and!T.!Brown,!Acs#Nano,!2012,!6,!9221]9228.! !

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22!

Professor*David*Buckingham*University!of!Cambridge,!United!Kingdom!!Professor! David! Buckingham! was! born! in! Sydney,!Australia!on!28!January!1930.!He!first!attended!between!1941]1947! the! Barker! College,! Hornsby,! N.S.W.,!Australia.! Then,! he! obtained! a! B.Sc.! with! First! Class!Honours!and!the!University!Medal!at!Sydney!University!in!1951.!In!1953,!he!was!researcher!in!physical!chemistry!under! Professor! R.! J.!W.! Le! Fèvre,! and!was! awarded! a!M.Sc.! Between! 1953]1955,! he! was! Shell! Postgraduate!Scholar! at! Corpus! Christi! College,! Cambridge.! He!obtained!his!PhD!in!theoretical!chemistry!under!Dr.!J.!A.!Pople! in! 1956.! ! Between! 1955]1957,! Buckingham! was!1851! Exhibition! Senior! Studentship! in! the! Physical!Chemistry!Laboratory,!Oxford!University.!Until!1965,!he!had!been!lecturer!and!subsequently!Student,!Tutor!and!Censor! of! Christ! Church,! Oxford! and! lecturer! in! the!Inorganic! Chemistry! Laboratory,! Oxford! University.! In!1965,! he! was! appointed! professor! of! Theoretical!Chemistry! in! Bristol! University.! In! 1969,! he! became!professor! of! Chemistry! in! Cambridge! University,! a!position!he!had!held!until!1997.!In!1997,!Buckingham!was!appointed!Emeritus!Professor!of!Chemistry! in!Cambridge!University.!He!has!been!Fellow!of!Pembroke!College,!Cambridge,!between! 1970! and! 1997,! when! he! became! Emeritus! Fellow,! and! subsequently! Honorary!Fellow!in!2005.!He!obtained!a!Sc.D.!in!Cambridge!University!in!1985.!!Among!his!accolades!and!fellowships!are:!Commander!of!the!British!Empire!(1997);!Fellow!of!the!Royal!Society!(elected!1975);!!Hughes!Medal!(1996);!Foreign!Associate!of!the!National!Academy!of!Sciences!(U.S.A.)!(1992);!Foreign!Honorary!Member!of!the!American!Academy!of! Arts! &! Sciences! (1992);! Foreign! Member! of! the! Royal! Swedish! Academy! of! Sciences!(1996);! Corresponding! Member! of! the! Australian! Academy! of! Science! (2008);! Doctor! of!Science! (Honoris! Causa),! Sydney!University! (1993);! Docteur!Honoris! Causa! de! l’Université!Nancy!I!(1979);!Doctor!of!Science!(Honoris!Causa),!University!of!Antwerp!(2004);!Member!of!the! International! Academy! of! Quantum! Molecular! Science! (1985);! Fellow! of! the! Royal!Australian!Chemical!Institute!(Rennie!Memmorial!Medal!1958);!Fellow!of!the!Royal!Society!of! Chemsitry! (Tilden! Lecturer! 1964,! Lennard]Jones! Lecturer! 1986,! Faraday! Medal! 1998);!Fellow!of!the!Institute!of!Physics!(Harrie!Massey!Medal!1995);!Fellow!of!the!Optical!Society!of!America!(C.!H!.!Townes!Award!2001);!Fellow!of!the!American!Physical!Society;!Inaugural!Ahmed!Zewail!Prize! for!Molecular!Sciences! (2007);!Cricket!Blue,!Sydney!University! (1952);!Senior! Treasurer! of! Oxford! University! Cricket! Club! (1958]1964);! President! of! Cambridge!University! Cricket! Club! (1990]1999);! Editor! of! Molecular# Physics! (1968]1972);! Editor! of!Chemical# Physics# Letters! (1978]1999);! Co]editor! of! International# Reviews# in# Physical#Chemistry!(1981]1989).!!He!has!married!Jillian!Bowles!in!1965!and!has!two!daughters!and!one!son.! !

!!

23!

Chiral*Discrimination*In*NMR*Spectroscopy***Nuclear!magnetic!resonance!is!perhaps!the!most!important!form!of!molecular!spectroscopy!in! chemistry! and! biochemistry.! Yet! it! is! blind! to! chirality! because! the! two! molecular!parameters!that!determine!the!NMR!spectrum,!namely!the!nuclear!magnetic!shielding!and!the! nuclear! spin]spin! coupling,! are! even! under! the! parity! operator! and! are! therefore!identical! for!a!molecule!and! its!mirror! image.! ! ! It!was!predicted! in!2004!(Chemical#Physics#Letters,! 2004,! 398,! 1]5)! that! precessing! nuclear! spins! in! chiral! molecules! in! a! liquid! in! a!strong!magnetic! field! induce!a!rotating!electric!polarization!perpendicular! to! the!magnetic!field!and!to!the!precessing!magnetization.!!!This!polarization!is!of!the!same!magnitude!but!of!opposite!sign! for!chiral!enantiomers!and!therefore!vanishes! for!achiral!samples.! ! ! It!arises!from! a! pseudoscalar! molecular! property! arising! from! the! distortion! of! the! electronic!structure!by!the!nuclear!magnetic!moment!in!the!presence!of!the!strong!magnetic!field!and!is!equivalent!to!the!linear!effect!of!an!electric!field!on!the!nuclear!shielding!tensor.!!!!!The!induced!electric!polarization!can!be!enhanced!by!two!or!three!orders!of!magnitude!in!dipolar!molecules!through!the!temperature]dependent!partial!orientation!of!the!permanent!dipole!via!the!antisymmetric!part!of!the!nuclear!magnetic!shielding!tensor.!!!An!alternative!method! for! the! detection! of! chirality! could! be! through! an! applied! electric! field! inducing!magnetization! perpendicular! to! the! field! and! to! the! precessing! magnetization.! ! ! This!!electric]field]induced! magnetization! is! of! equal! magnitude! and! of! opposite! sign! for!enantiomers;! ! it! is! determined! by! the! same! parameters! that! give! the! precessing! electric!polarization.! For! small! molecules! these! pseudoscalar! properties! are! amenable! to!computation.! ! ! In! a! chiral! sample! every! NMR! spectral! line! has! an! associated! positive! or!negative! signal! at! the! same! frequency,! just! as! in! circular! dichroism,! vibrational! circular!dichroism!and!Raman!optiocal! activity.! ! ! Progress! towards! the!experimental! realization!of!chiral! discrimination! in! NMR! spectroscopy,! being! carried! out! at! the! CNRS! High!Magnetic!Field!Laboratory!in!Grenoble,!will!be!reported.! !

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25!

Small*Molecules*For*Signaling*In*The*Brain*

!

Since!the!late!50s,!it!has!been!realized!that!nerve!cells!communicate!using!small!messenger!molecules,! such! as! amino! acids! and!monoamines,! and! that! one!may! achieve! remarkable!improvement! in! a! number! of! psychiatric! and! neurological! disorders! by! enhancing! or!dampening!the!activity!of!these.!After!a!brief!review!of!the!development!in!this!field!during!the! past! 60! years,! the! necessity! to! introduce! a! new! way! of! interfering! with! brain!neurotransmitters,!i.e.!that!of!stabilisation!(rather!than!mere!activation!or!blockade),!will!be!discussed.! As! an! example! of! this! new! concept,! recent! results! obtained! with! a! dopamine!stabilizer,!OSU61612,!will!be!presented.!

!

Presented*together*with:*

Professor*Elias*Eriksson*Gothenburg!University,!Sweden!

Elias!Eriksson!is!pharmacologist!at!the!University!of!Gothenburg!with! a! long]standing! interest! in! preclinical! and! clinical!psychopharmacology,! psychoendocrinology! and! psychiatric!genetics.!

*

! !

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26!

Professor*Wah*Chiu*Baylor!College!of!Medicine,!United!States!!Dr.! Wah! Chiu! received! his! BA! in! Physics! (1969)! and!PhD! in! Biophysics! (1975)! from! the! University! of!California,! Berkeley.! He! is! the! Alvin! Romansky!Professor!of!Biochemistry!and!Director!of!the!National!Center! for!Macromolecular! Imaging! at! Baylor! College!of! Medicine.! ! Dr.! Chiu! is! a! pioneer! in! methodology!development! for! electron! cryo]microscopy.! His! work!has! made! a! transformational! contribution! towards!developing! the! use! of! single! particle! electron! cryo]microscopy! as! a! routine! tool! for! the! structural!determination!of!macromolecular!machines!at!atomic!resolution.! Dr.! Chiu’s! NIH! funded! 3DEM! Resource!Center! has! solved! structures! of! viruses,! chaperonins,!ion! channel! proteins,! molecular! pumps,! cytoskeleton!bundles! and! nuclear! receptor! complexes! in!collaboration!with!many!scientists!around!the!world.!!Dr.! Chiu! is! the! founding! director! of! the! Graduate!Program! in!Structural! and!Computational!Biology!and!Molecular!Biophysics!at!Baylor!College!of!Medicine.!!He!is!also!the!founding!Co]Director!of!the! Gulf! Coast! Consortia,! which! includes! Baylor! College! of! Medicine,! Rice! University,!University!of!Houston,!University!of!Texas!Houston!Medical!School,!M.D.!Anderson!Cancer!Center! and! University! of! Texas! Galveston!Medical! Branch.! His! active! involvement! in! the!establishment!of! the!educational!and!research!training! infrastructure! in! the!Houston!Area!has!created!a!unique!and!valuable!environment! for!cross]disciplinary!collaboration!among!faculty!from!multiple!academic!departments!and!institutions.!!Dr.! Chiu! has! earned! several! honors! over! the! years! including! the! Distinguished! Service!Professorship!at!Baylor!College!of!Medicine!in!2010;!the!Distinguished!Faculty!Award!from!the!Baylor!College!of!Medicine!Alumni!Association!in!2013;!the!Distinguished!Science!Award!from!the!Microscopy!Society!of!America!in!2014;!and!the!Honorary!Doctorate!of!Philosophy,!University! of! Helsinki,! Finland! in! 2014.! He! was! an! elected! member! of! Academia! Sinica,!Taiwan!in!2008;!the!United!States!National!Academy!of!Sciences!in!2012;!and!the!Academy!of!Medicine,!Engineering,!and!Science!of!Texas!in!2013.!! !

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27!

Electron*CryoNMicroscopy*of*Molecular*Machines**!Electron! cryo]microscopy! (cryoEM)! is! in! the!midst!of! a! revolutionary! advance! in! resolving!the!biological!structures!of!molecular!machines!at!resolutions!previously!either!difficult!or!impossible!to!attain.!We!owe!this!achievement!partly!to!direct!electron!detectors!capable!of!recording!electron!images!of!frozen,!hydrated!molecular!machines!with!enhanced!signal!to!noise! ratio! at! a! full! range! of! spatial! frequencies.! In! addition,! the! availability! of! many!different!image!processing!software!packages!for!3D!reconstruction!contributed!freely!from!many! academic! labs! has! facilitated! structure! solution.! In! our! laboratory,! we! have! solved!cryoEM! structures! of! molecular! machines,! including! viruses,! chaperonins,! protein!complexes! and! ion! channels,! where! either! partial! or! full]atom! models! of! the! protein!components! can! be! derived! from! the! cryoEM! maps.! We! have! implemented! multiple!protocols!to!evaluate!the!reliability!of!these!structures,!which!are!comparable!to!structures!solved!by!X]ray!crystallography!at!equivalent!resolutions.!Because!cryoEM!does!not!require!crystallization,! we! can! readily! determine! multiple! structures! of! the! same! molecular!machines! in! different! biological! or! biochemical! states.! In! some! cases,! the! specimen! of!molecular!machines!may!have!either!compositional!or!conformational!heterogeneity.!!!Computational! classifications! of! the! images! can! be! applied! to! sort! out! the! images! into!different!subpopulations!so!that!distinct!structures!can!be!derived!from!a!single!specimen!at!subnanometer! resolutions.! Such! an! approach! is! unique! in! cryoEM! relative! to! other!structural!tools!to!reveal!the!mechanisms!of!biological!functions!and!the!assembly!principles!of! molecular! machines! in! a! structurally! impure! sample.! In! addition! to! examining! high!resolution! structures! of! biochemically! purified! molecular! machines,! the! tomographic!approach! has! been! developed! to! determine! their! structures! in! cells! or! cell]like!environments!at!medium!resolution.!The!structures!of!molecular!machines!determined!both!in! vitro! and! in! vivo! by! cryoEM! provide! a! unique! view! of! structural! plasticity! for!understanding!physiological!processes.! !

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28!

Professor*Peter*Dervan*California!Institute!of!Technology,!United!States!

!

Peter!B.!Dervan! is! the!Bren!Professor!of!Chemistry!at!the! California! Institute! of! Technology.! ! Dervan!pioneered! a! field! of! chemistry! with! studies! directed!toward!understanding! the! chemical! principles! for! the!sequence!specific!recognition!of!DNA.!!Cell!permeable!small!molecules!that!modulate!protein]DNA!interfaces!may! be! useful! for! the! external! control! of! aberrant!gene! expression! relevant! in! human! disease.! ! Dervan!received! his! B.S.! degree! from! Boston! College,! and!Ph.D.!at!Yale.!!He!was!a!postdoctoral!fellow!at!Stanford!University!and!began!his!association!with!Caltech!as!an!assistant!professor! in! 1973.! ! Professor!Dervan! served!as!chair!of!Caltech’s!division!of!chemistry!and!chemical!engineering!from!1994!to!1999.!He!is!a!member!of!the!National! Academy! of! Sciences,! the! Institute! of!Medicine,!the!American!Academy!of!Arts!and!Sciences,!and! the! American! Philosophical! Society,! a! Foreign!Member! of! the! French! Academy! of! Sciences! and! the!German!National!Academy!of!Sciences.!!Professor!Dervan!received!the!2006!National!Medal!of!Science!from!President!Bush.!!!

Other! awards! include! the! Harrison! Howe! Award! (1988),! Arthur! C.! Cope! Award! (1993),!Willard!Gibbs!Medal! (1993),!Nichols!Medal! (1994),!Maison!de! la! Chimie! Foundation!Prize!(1996),! Remsen! Award! (1998),! Kirkwood!Medal! (1998),! Alfred! Bader! Award! (1999),! Max!Tishler! Prize! (1999),! Linus! Pauling! Medal! (1999),! Richard! C.! Tolman! Medal! (1999),!Tetrahedron!Prize!(2000),!Harvey!Prize!(Israel)!(2002),!Ronald!Breslow!Award!(2005),!Wilbur!Cross!Medal! (2005)!and!the!Frank!H.!Westheimer!Medal! (2009).! !Dervan! is!considered!an!outstanding! teacher!having!won!several!“excellence! in! teaching!awards”! from!the!Caltech!undergraduates.!He!served!on!several!Scientific!Advisory!Boards!for!the!pharmaceutical!and!biotechnology!industries.!!He!is!Chair!of!the!Scientific!Advisory!Board!of!the!Robert!A.!Welch!Foundation.! !

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29!

Transcription*Factor*Antagonists:*From*Discovery*to*Oncology*

!

Pyrrole]imidazole!(Py]Im)!polyamides!are!synthetic!molecules!programmed!to!read!the!DNA!double!helix!by!a!set!of!simple!chemical!principles.!!These!cell!permeable!oligomers!achieve!affinities! comparable! to! DNA]binding! proteins.! ! Research! efforts! are! focused! on! the!modulation! of! gene! expression! pathways! by! disruption! of! transcription! factor]DNA!interfaces.! The! oversupply! or! overactivity! of! one! or! more! transcription! factors! may! be!required!for!the!survival,!growth,!and!metastatic!behavior!of!all!human!cancers.! !An!x]ray!crystal! structure!of! an!eight]ring! cyclic! Py]Im!polyamide•DNA!complex! reveals! the! role!of!allosteric!alteration!of!DNA!structure!as!a!mechanism!for!disruption!of!transcription!factor]DNA!interfaces.!

Prostate!cancer!is!the!second!leading!cause!of!cancer!death!in!men.!!The!disease!is!primarily!driven! by! the! dysregulated! activity! of! the! androgen! receptor.! ! The! current! treatment! for!metastatic!prostate!cancer!utilizes!a!combination!of!drugs! that!antagonizes! the!activity!of!the! androgen! receptor! (AR)! collectively! called! androgen! deprivation! therapy! (ADT).! ADT!functions! by! blocking! AR! signaling! through! the! interference! of! DHT]AR! interactions!(bicalutamide,! enzalutamide)! or! by! depleting! levels! of! DHT! (abiraterone)! or! its! precursor!testosterone! (leuprolide).!While! effective,! relapse! is! often! the! inevitable! outcome!of!ADT!due!to!mutations!to!AR!and!presence!of!redundant!pathways,!such!as!the!replacement!of!lost!AR!signaling!by!glucocorticoid!receptor!(GR).!

Due!to!the!necessity!for!DNA!binding!for!the!activation!of!AR!signaling,!one!potential!way!to!attenuate! transcription!programs! that! drive! disease!progression! is! to! target! the!DNA!and!block!protein]DNA!interactions!of!nuclear!hormone!receptors!and!their!respective!response!elements!through!the!use!of!Py]Im!polyamides.!!These!molecules!have!been!shown!to!affect!gene!expression! in! transcription!networks,! including! those! induced!by!AR!and!GR!without!genotoxicity.!Additionally,!polyamides!are!able!to!interfere!with!DNA!dependent!processes!like!the!RNA!polymerase!II!elongation!and!DNA!polymerase!replication.!They!have!also!been!shown! to! exhibit! antitumor! activity! in! prostate! cancer! cell! lines! and! xenograft!models! of!castration!resistant!prostate!cancer!with!minimal!toxicity!to!the!host!animals.!! !

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30!

Professor*Chris*Dobson*University!of!Cambridge,!United!Kingdom!

!

Chris! Dobson! was! an! undergraduate,! graduate!student! and! research! fellow! in! chemistry! at! the!University! of! Oxford.! In! 1977! he! moved! to!Harvard! as! an! assistant! professor! of! chemistry!and!was!also!a!visiting! scientist!at!MIT.!He! then!returned! to! Oxford! as! a! lecturer,! and! later!became! professor! of! chemistry! and! Director! of!the! Oxford! Centre! for! Molecular! Sciences.! In!2001!he!moved!to!the!University!of!Cambridge!as!the! John! Humphrey! Plummer! Professor! of!Chemical! and! Structural! Biology.! He! is! also!Master! of! St! John’s! College! and! Director! of! the!recently! established! Cambridge! Centre! for!Misfolding!Diseases.!!!His! research! interests! are! focused! on! protein!molecules! and! particularly! on! defining! the!fundamental! principles! by! which! they! fold! to!generate! function! and! activity,! and! yet! can!misfold! to! generate! toxicity! and! disease.! His!research! group!makes! use! of! a! very!wide! rang! of! techniques,! involving! theory! as!well! as!experiment,! and! is! also! highly! collaborative.! He! has! been! particularly! interested! in! the!discovery!of! the!nature,!properties,!mechanism!of! formation!and!biological!significance!of!the! amyloid! state! of! proteins! and! in! defining! its! links! with! neurodegenerative! disorders!including!Alzheimer’s!and!Parkinson’s!disease.!He!is!a!Fellow!of!the!Royal!Society!of!London!and! of! the!UK! Academy! of!Medical! Sciences,! and! a! Foreign! Associate! of! the!US!National!Academy!of!Sciences.!He!is!the!recipient!of!a!range!of!awards!including!the!Davy!and!Royal!Medals! of! the! Royal! Society! and!most! recently! the! 2014!Heineken! Prize! for! Biochemistry!and! Biophysics! from! the! Royal! Netherlands! Academy! of! Arts! and! Sciences,! and! the! 2014!Feltrinelli!International!Prize!for!Medicine!from!the!Accademia!Nazionale!dei!Lincei!in!Rome.! !

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31!

The*Amyloid*Phenomenon*and*its*Significance*!Protein! folding! is! an! essential! step! in! the! generation! of! biological! functionality! within! all!living! systems,! and! much! is! now! understood! about! the! underlying! mechanism! of! this!complex!and!ubiquitous!process.! Proteins! can,!however,!misfold!or! fail! to! remain! in! their!correctly! folded!states,!and! in!some!such!cases!this! results! in! the! formation!of! intractable!aggregates! known! as! amyloid! fibrils.! Interest! in! this! phenomenon! has! developed! with!extraordinary! rapidity! in! recent! years,! primarily! because! of! the! links! between! amyloid!formation!and!a! range!of! rapidly!proliferating!medical! disorders.!More! than! fifty!diseases!are!now!linked!to!this!phenomenon!and!include!neurological!disorders!such!as!Alzheimer’s!disease,!non]neuropathic!organ!specific!disorders! such!as! type! II!diabetes,!and!a! range!of!systemic! amyloidoses.! Although! some! of! these! types! of! disease! are! rare,! others! are!increasingly! common! as! a! result! of! rapidly! changing! lifespans! and! lifestyles;! worldwide,!some!40!million!people!are!estimated!to!be!suffering!from!Alzheimer’s!disease!and!nearly!400!million! from! type! II!diabetes.! In!addition! to! its! significance! for!disease,!however,! it! is!increasingly!clear!that!understanding!the!balance!between!folding!and!misfolding!gives!new!and! important! insights! into! the!nature!of! functional!protein!molecules!and!the!process!of!biological! evolution.! This! talk!will! provide! an!overview!of! this! field!of! science! and!discuss!recent!progress! in!our!knowledge!of! the!structural!and!physical!properties!of! the!amyloid!state,! the!kinetics!and!mechanism!of! its! formation,!the!nature!and!origins!of! its! links!with!disease!and!the!manner!in!which!such!links!can!be!inhibited!or!suppressed.! !

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Professor*Andrew*Fire*Stanford!University,!United!States!!A! native! of! Santa! Clara! County,! California,! Dr.! Fire!recieved! training! at! UC! Berkeley! (Mathematics! BA:!1975]1978),!MIT!(Biology!Ph.D.:!1978]1983),!and!the!Medical! Research! Council! Laboratory! in! Cambridge!UK! (Postdoctoral:! 1983]1986).! !From! 1986! to! 2003,!Dr.! Fire!was!on! the! staff!of! the!Carnegie! Institution!of! Washington's! Department! of! Embryology! in!Baltimore! Maryland.! !During! his! time! in! Baltimore,!Dr.!Fire!assumed!the!position!of!Adjunct!Professor!of!Biology!at!Johns!Hopkins!University.!!In!2003,!Dr.!Fire!joined! the! faculty! of! the!Departments! of! Pathology!and! Genetics! at! Stanford! University! School! of!Medicine.! !

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Taming*Opportunistic*Rnas*!The! genetic! landscape! faced! by! a! living! cell! is! constantly! changing.!! Developmental!transitions,! environmental! shifts,! and! pathogenic! invasions! lend! a! dynamic! character! to!both!the!genome!and! its!activity!pattern.!!A!variety!of!natural!mechanisms!are!utilized!by!cells! adapting! to! genetic! change,! with! the! needs! of! cells! to! distinguish! "self"! versus!"nonself"!and!"wanted"!versus!"unwanted"!gene!expression!at!the!presumed!root!of!both!successful!development!and!pathogen!defense.!!Experiments!in!which!foreign!RNA!or!DNA!is! introduced! into! cells! provide! a! window! with! which! to! study! these! mechanisms.!! In!particular,!such!approaches!have!unexpectedly!allowed!the!characterization!of!a!number!of!structural!features!that!provide!an!indication!of!unwanted!nucleic!acid.!!!!One! of! these! features! has! been! double! stranded! RNA! (dsRNA).!! Absent! during! "normal"!gene! expression,! dsRNA! is! an! essential! component! in! the! life! cycle! of! most! viruses.!! By!flagging!dsRNA!as!an! indicator!of!unwanted!RNA!replication,!and!by!scrupulously!avoiding!the!production!of!dsRNA!during!most!normal!gene!expression,!the!cell!acquires!a!modicum!of!protection!from!viral!infection.!!The!mechanism!by!which!dsRNA!segments!are!utilized!to!trigger!silencing!of!homologous!genes!is!of!interest!as!a!fundamental!biological!process,!as!a!basis! for! effective! genetic! tools,! and! as! an! exemplar! of! a! structure]based! defense!mechanism!in!eukaryotic!cells.! !

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Professor*Harry*Gray*California!Institute!of!Technology,!United!States!!Harry! Gray! is! the! Arnold! O.! Beckman! Professor! of!Chemistry!and!the!Founding!Director!of!the!Beckman!Institute! at! the! California! Institute! of! Technology.!After! graduate! work! in! inorganic! chemistry! at!Northwestern! University! and! postdoctoral! research!at! the! University! of! Copenhagen,! he! joined! the!chemistry! faculty! at! Columbia! University,! where! in!the!early!1960s!he!developed! ligand! field! theory! to!interpret! the! electronic! structures! and! reactions! of!transition!metal!complexes.!After!moving!to!Caltech!in! 1966,! he! began! work! in! biological! inorganic!chemistry! and! inorganic! photochemistry! that! led! to!the! development! of! molecular! systems! for! the!storage! of! solar! energy.! During! investigations! of!metalloprotein! redox! reactions! in! the! 1980s,! he!demonstrated!that!electrons!can!tunnel!rapidly!over!long!molecular!distances!through!folded!polypeptide!structures.! This! discovery! opened! the! way! for!experimental!and!theoretical!work!that!shed!new!light!on!the!mechanisms!of!electron!flow!through!proteins!that!function!in!respiration!and!photosynthesis.!!Gray!has!published!over!850! research!papers!and!18!books.!He!has! received! the!National!Medal! of! Science! from! President! Ronald! Reagan! (1986);! the! Pauling! Medal! (1986);!the!Linderstrøm]Lang!Prize! (1992);! the! Gibbs! Medal! (1992);! the! Harvey! Prize! (2000);! the!Nichols!Medal!(2003);!the!National!Academy!of!Sciences!Award!in!Chemical!Sciences!(2003);!the!Benjamin!Franklin!Medal! in!Chemistry! (2004);! the!Wolf!Prize! in!Chemistry! (2004);! the!City!of!Florence!Prize! in!Molecular!Sciences!(2006);! the!Welch!Award! in!Chemistry! (2009);!the! Japan! International! Coordination! Chemistry! Award! (2010);! the! Othmer! Gold! Medal!(2013);! the!T.!W.!Richards!Medal! (2014);!six!national!awards! from!the!American!Chemical!Society,! including! the!Priestley!Medal! (1991);! and!18!honorary!doctorates,! including!ones!from! Chicago,! Columbia,! Pennsylvania,! Toulouse,! Florence,! Copenhagen,! Göteborg,!Edinburgh,!and!the!Weizmann!Institute!of!Science.!He!is!a!member!of!the!National!Academy!of! Sciences;! the! American! Academy! of! Arts! and! Sciences;! the! American! Philosophical!Society;!a!foreign!member!of!the!Royal!Danish!Academy!of!Sciences!and!Letters;!the!Royal!Swedish! Academy! of! Sciences;! the! Royal! Society! of! Great! Britain;! and! the! Accademia!Nazionale!dei!Lincei.!He!is!a!Director!of!University!Science!Books!and!Chair!of!the!Board!of!Directors!of!the!Arnold!and!Mabel!Beckman!Foundation.!!! !

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The*Currents*of*Life:*Electron*Flow*through*Proteins**Biological! electron! transfers! often! occur! between!metal]containingcofactors! that! are!separated! by! very! large! molecular! distances.! Understanding! the! underlying! physics! and!chemistry! of! these! electron! transfer! processes! is! the! goal! of! much! of! the! work! in! my!laboratory.! Employing! laser!flash]quench!triggering! methods,! my! coworkers! and! I! have!shown! that!2]nm,!coupling]limited!Fe(II)! to! Ru(III)! and! Cu(I)! to! Ru(III)! electron! tunneling!reactions! in!Ru]modified!cytochromes! and! blue! copper! proteins! occur! on!microsecond! to!nanosecond!timescales.!!!We!also!have!demonstrated!that!redox!equivalents!can!be!transferred!even!longer!distances!by!multistep!tunneling!(hopping)!through!intervening!tyrosines!and!tryptophans:!notably,!in!work!on!cytochrome!P450!and!azurin,!we!have!found!that!long]range!hole!hopping!through!intervening!tryptophans!can!be!orders!of!magnitude!faster!than!single]step!tunneling.!Based!on!these!findings,!we!think!it!likely!that!hole!hopping!through!Tyr/Trp!chains!could!protect!oxygenase! and! peroxidase! enzymes! from! oxidative! damage.! In! support! of! this! view,! by!examining! the! structures! of! P450! (CYP102A1)! and!2OG]Fe!(TauD)! enzymes,! we! have!identified! candidate! Tyr/Trp! chains! that! could! transfer! holes! from! uncoupled!high]potential!intermediates!to!reductants!in!contact!with!protein!surface!sites.!! !

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Professor*Stefan*Hell*University!of!Göttingen,!Germany!!Stefan! W.! Hell! is! a! director! at! the!Max! Planck!Institute! for! Biophysical! Chemistry!in! Göttingen,!where! he! leads! the! Department! of!NanoBiophotonics.! He! is! an! honorary! professor! of!experimental! physics! at! the!University! of!Göttingen!and! adjunct! professor! of! physics! at!theUniversity! of! Heidelberg.!Since! 2003! he! also! led!the!Optical! Nanoscopy! division!at! the!German!Cancer!Research!Center!(DKFZ)!in!Heidelberg.!!Stefan! W.! Hell! received! his! diploma! (1987)! and!doctorate! (1990)! in! physics! from! the! University! of!Heidelberg.! From! 1991! to! 1993! he! worked! at! the!European! Molecular! Biology! Laboratory,! also! in!Heidelberg,! and! followed! with! stays! as! a! senior!researcher! at! the! University! of! Turku,! Finland,!between!1993!and!1996,!and!as!a!visiting!scientist!at!the!University! of! Oxford,! England,! in! 1994.! In! 1997!he! was! appointed! to! the! MPI! for! Biophysical!Chemistry!in!Göttingen!as!a!group!leader!and!was!promoted!in!2002!to!director.!!Stefan! W.! Hell! is! credited! with! having! conceived,! validated! and! applied! the! first! viable!concept! for! overcoming! Abbe’s!diffraction]limited!resolution! barrier! in! a!light]focusing!fluorescence!microscope.!For!this!accomplishment!he!has!received!several!awards:!most! recently! he! shared! the! 2014! Kavli! Prize! in! Nanoscience! and! the! Nobel! Prize! in!Chemistry.!! !

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Nanoscopy*With*Focused*Light*!Throughout!the!20th!century!it!has!been!widely!accepted!that,!at!the!end!of!the!day,!a!light!microscope!relying!on!conventional! lenses! (far]field!optics)!cannot!discern!details! that!are!finer! than! about! half! the!wavelength! of! light! (>! 200! nm).! However,! in! the! 1990s,! it! was!discovered!that!overcoming!the!diffraction!barrier! is!realistic!and!that!fluorescent!samples!can! be! resolved! virtually! down! to!molecular! dimensions.! Here!we! discuss! the! simple! yet!powerful! principles! that! allow! neutralizing! the! resolution]limiting! role! of! far]field! optical!diffraction1,2.!In!a!nutshell,!features!residing!closer!than!the!diffraction!barrier!are!prepared!in!different!molecular!(quantum)!states!so!that!they!are!distinguishable!for!a!brief!detection!period.!As!a!result,!the!resolution]limiting!role!of!diffraction!is!overcome,!and!the!interior!of!transparent! samples,! such!as! living! cells! and! tissues! can!now!be! imaged!non]invasively!at!the!nanoscale!using!focused!light!in!3D.!!!Besides! discussing! basic! principles,! we! will! show! recent! advancements.! In! particular,! we!demonstrate!massive!parallelization!of!RESOLFT!and!STED!recording!using!simple!patterns!of! light,!by!more!than!100,000!fold3.!Likewise,!we!demonstrate!the!relevance!of!emerging!‘far]field!optical!nanoscopy’!to!various!areas,!especially!to!the!life!and!the!material!sciences!!1.! Hell,!S.W.!Far]Field!Optical!Nanoscopy.!Science!316,!1153]1158!(2007).!2.! Hell,!S.W.!Microscopy!and!its!focal!switch.!Nature#Methods!6,!24]32!(2009).!3.! Chmyrov,!A.!et!al.!Nanoscopy!with!more!than!100,000!'doughnuts'.!Nature#Methods!(2013).!! !

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Professor*Richard*Henderson*MRC!LMB,!Cambridge,!United!Kingdom!!Richard! Henderson! (b.! 1945)! is! a! structural!biologist.! ! After! an! undergraduate! degree! in!physics! and! initial! X]ray! work! on! the! enzyme!chymotrypsin,! he! studied! membrane! protein!structure.! ! With! Nigel! Unwin,! he! developed!electron! crystallographic! methods! for! structural!analysis!of!two]dimensional!crystals!and!used!them!to! determine! the! atomic! structure! of!bacteriorhodopsin! and! to! study! the! structural!changes!that!underlie!light]driven!proton!pumping!by!bacteriorhodopsin.!!For!this!work,!he!and!Unwin!received! the! Gregori! Aminoff! prize! for!Crystallography! from! the! Royal! Swedish! Academy!in! 1999.! ! His! recent! focus! is! on! single! particle!electron! cryomicroscopy! to! determine! atomic!structures!of!macromolecular! complexes,!which! is!now!delivering!on!its!early!promise!of!determining!atomic! structures! of! large! protein! assemblies!without!crystallisation.!!Alongside! his! academic! work,! with! Chris! Tate,! he! helped! to! develop! the! idea! of!conformational!thermostabilisation!of!membrane!proteins!by!systematic!mutagenesis.!!This!made!the!proteins!much!more!stable!so!that!they!could!be!crystallised.!!The!most!notable!successes! of! this! approach! have! been! the! atomic! structure! determinations! of! three! G]protein! coupled! receptors! (GPCRs)! at!MRC]LMB,! alongside! the! setting! up! of! a! structure]based!drug!design!company!Heptares!Therapeutics,!which!works!on!many!other!GPCRs.!!He!was!Joint]Head!of!the!Division!of!Structural!Studies!at!MRC]LMB!from!1986!until!2000,!and!Director!from!1996!until!2006.!!Since!2006,!he!has!returned!to!full]time!scientific!research.!!! !

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Structure*Of*Membrane*Proteins*Involved*In*Signal*Transduction*!I!will!show!three!different!approaches!to!the!determination!of!the!structure!of!membrane!proteins! and! present! examples! of! some! interesting! structures! of! membrane! proteins!involved!in!signal!or!energy!transduction!that!have!been!determined!by!each!method.!!The!three! methods! are! electron! crystallography! of! two]dimensional! (2D)! crystals,! X]ray!crystallography! of! three]dimensional! (3D)! crystals,! and! single! particle! electron!cryomicroscopy.! ! Each! one! of! these! approaches! has! corresponding! strengths! and!weaknesses.!!!

The!structure!2D!crystals!of!bacteriorhopsin!was!first!solved!by!electron!crystallography!in!1990! and! since! then!many! related! structures! have! been! determined.! ! The! ability! to! trap!photocycle!intermediates!is!a!key!tool!in!understanding!the!structural!changes!that!underlie!the!mechanism!of!proton!pumping,!and!these!same!structural!changes!are!involved!in!signal!transduction!by!other!members!of!the!same!family.!!

An!approach!to!the!determination!of!the!structure!of!G!protein]coupled!receptors!(GPCRs)!has! involved! a! method! called! conformational! thermostabilisation! in! which! systematic!mutagenesis!is!used!to!improve!the!stability!of!a!particular!GPCR!in!detergent,!so!that!it!can!be! induced! to! form!3D!crystals.! !This!method,!developed! in!collaboration!with!Chris!Tate,!has!been!used! to!produce! crystals! and!determine! the! structures!of!3!GPCRs!at!MRC]LMB!and!a!much!larger!number!at!Heptares,!a!company!set!up!to!use!this!approach!to!carry!out!structure]based!design!of!new!drugs!for!therapeutic!use.!

Most!recently,!single!particle!electron!cryomicroscopy!has!reached!the!stage!where!atomic!resolution! maps! can! be! obtained! from! macromolecular! complexes! without! the! need! to!produce! either! 2D! or! 3D! crystals.! ! Two! structures! determined! recently! at! MRC]LMB! are!those!of!bovine!mitochondrial!Complex!I!by!Vinothkumar!in!collaboration!with!Judy!Hirst’s!group! in! the! MRC! Mitochondrial! Biology! Unit! in! Cambridge,! and! the! enzyme! gamma]secretase!by!the!group!of!Sjors!Scheres!in!collaboration!with!the!group!of!Yigong!Shi!from!Tsinghua!University!in!Beijing.! !

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Professor*Wayne*Hendrickson*Columbia!University,!United!States!!Wayne!A.!Hendrickson!is!a!University!Professor!at!Columbia!University.!!He!has!a!B.A.!from!the!University! of! Wisconsin! at! River! Falls! and! a!Ph.D.! in! biophysics! from! Johns! Hopkins!University! based! on! work! with! Warner! Love.!!His! postdoctoral! research! was! with! Jerome!Karle! at! the!Naval! Research! Laboratory! (NRL).!!He!remained!at!NRL!as!a!Research!Biophysicist!until! 1984!when! he! joined! the!Department! of!Biochemistry! and! Molecular! Biophysics! at!Columbia.! ! Hendrickson! was! also! an! HHMI!Investigator! from! 1986! to! 2012;! in! 2008,! he!was! named! the! Violin! Family! Professor! of!Physiology!and!Cellular!Biophysics;!and!in!2010,!he! became! the! Scientific! Director! of! the! New!York!Structural!Biology!Center.!!Research! in! Dr.! Hendrickson's! laboratory!focuses! on! the! structure! and! function! of!biological!molecules.! ! He! and! his! colleagues! use! x]ray! crystallography! to! study!molecular!properties!in!atomic!detail.!!By!analyzing!x]ray!beams!diffracted!from!crystals,!they!are!able!to! reconstruct! images! of! crystallized! molecules.! ! Their! advances! in! diffraction! methods!(notably,! stereochemically! restrained! refinement,! phase! evaluation! from! anomalous!diffraction,! selenomethionyl! proteins,! and! synchrotron! instrumentation)! have! been!instrumental!in!the!emergence!of!structural!biology!as!a!major!force!in!modern!biology!and!molecular!medicine.! !They!use! this! technology! themselves! in! investigations!on!membrane!receptors! and! cellular! signaling,! on! viral! proteins! and! HIV! infection,! on! molecular!chaperones!and!protein!folding,!and!in!structural!genomics!of!membrane!proteins.!! !Dr.!Hendrickson!has!published!numerous!research!articles!and!related!reviews.! !He!serves!on!advisory!bodies! for! various! scientific!organizations.! !He! is! a! founding!editor!of!Current#Opinion# in# Structural# Biology! and! of! Structure,! and! he! was! a! founder! of! SGX!Pharmaceuticals.! ! His! honors! include! the!Aminoff! Prize! of! the!Royal! Swedish!Academy!of!Sciences,! the!Gairdner! International!Award,!and! the!Harvey!Prize!of! the!Technion!–! Israel!Institute!of!Technology.!!He!is!a!fellow!of!the!American!Academy!of!Arts!and!Sciences!and!a!member!of!the!National!Academy!of!Sciences.! !

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Distinctions*and*Shared*Principles*in*Transmembrane*Ion*Channels*

We!have!determined!atomic]level! structures! for! several!proteins! that!conduct! ions!across!lipid!bilayers.! !Structure]inspired!hypotheses!have!then!been!tested!in!functional!analyses,!often! both! for! a! prokaryotic! homolog! giving! initial! structures! and! also! for! a! well!characterized! eukaryotic! counterpart.! ! The! distinctive! architectural! features! of! these!channels!will!be!described,!and!mechanistic!principles!in!common!will!be!discussed.!!!

Results!will! be! shown! from! five! systems:! (1)! SLAC1! anion! channels! control! the! closing! of!stomatal!pores!in!plant!leaves,!and!homologous!proteins!are!found!in!bacteria!and!archaea.!!We! solved! the! crystal! structure! of! a! Haemophilus! homolog! at! 1.2! Å! resolution,! and! we!performed!mutational! analyses!of! channel! function! in! electophysiological! assays!with! this!protein! and!with!Arabadopsis#SLAC1! (Chen!et# al.,!Nature! 467,! 1074,! 2010).! ! (2)! CysZ! is! a!prokaryotic! sulfate! permease,! which! functions! as! an! ion! channel.! ! We! solved! crystal!structures!of!CysZ!proteins!from!three!bacterial!species,!and!we!gained!mechanistic!insights!from!mutational!analyses!of!sulfate!uptake!and! ion!currents! (Liu!et#al.,#Science!336,!1033,!2012;! Assur! et# al.,! submitted).! ! (3)! Bax! inhibitor]1! (BI]1)! is! an! antiapoptotic! protein! that!mediates! a! calcium! leak! and! is! representative! of! a! widely! distributed! family! of!transmembrane]Bax]inhibitor]motif! (TMBIM)! proteins.! ! Our! crystal! structures! are! of! a!Bacillus!BI]1!homolog,!and!we!characterized!the!pH!dependence!of!calcium!uptake!into!cells!and! proteoliposomes! (Chang! et# al.,# Science# 344,! 1131,! 2014).! ! (4)! Human! bestrophin]1!(Best1)!is!a!calcium]activated!chloride!channel!from!the!retinal!pigment!epithelium,!where!mutations!are!associated!with!macular!degeneration!disease.! !Our!crystal!structure! is!of!a!Klebsiella! homolog,! and! we! performed! mutational! analyses! of! channel! activity! in! this!bacterial! bestrophin! and! in! human! Best1! (Yang! et# al.,# Science# 346,! 355,# 2014).! ! (5)!Ryanodine! receptors! (RyRs)!mediate! the! rapid! release!of! calcium!stores! from! intracellular!compartments! into! the! cytosol,! which! is! essential! for! excitation]contraction! coupling! in!muscle.! ! Our! structures!were! determined! by! cryo]electron!microscopy! for! rabbit! skeletal!muscle!RyR1,! first! in! its! channel]closed! state! (Zalk!et# al.,#Nature#517,! 44! 2015)! and!more!recently!also!in!open!states!down!to!3.8!Å!resolution.!

.! !

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Professor*Roger*Kornberg*Stanford!University,!United!States!!Roger! Kornberg! is!Winzer! Professor! in!Medicine! and!Professor!of! Structural!Biology!at! Stanford!University.!!He! received! a! bachelor’s! degree! in! chemistry! from!Harvard!College!in!1967!and!a!Ph.D.!in!chemistry!from!Stanford! in! 1972.! ! His! first! research! was! on! the!dynamics! of! lipid! bilayers.! ! He! used! nuclear! and!electron! paramagnetic! resonance! to! determine! the!rates! of! diffusional!motions! of! lipids,! termed! flip]flop!and! lateral! diffusion.! ! He! then! turned! to! X]ray!diffraction! of! chromatin! and,! in! 1974,! proposed! the!existence! and! structure! of! the! nucleosome.! ! This!proposal! was! borne! out! in! detail! by! subsequent!structural!studies.!!!!Kornberg! moved! to! his! present! position! in! 1978,!where!his!research!has!focused!on!the!mechanism!and!regulation!of!eukaryotic!gene!transcription.!!Results!of!this!research!include!the!near!atomic!structure!of!RNA!polymerase! II,! the!elucidation!of! the!RNA!polymerase!II!transcription!machinery,!and!the!discovery!of!the!Mediator!of!transcriptional!regulation.!!Parallel!studies!of!metal!clusters!have!included!atomic!structures!large!gold!nanoparticles!by!X]ray!crystallography!and!aberration]corrected!electron!microscopy.! !

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Gold*Nanoparticles*For*CryoNElectron*Microscopy*!We!became!interested!almost!twenty!years!ago!in!the!attachment!of!gold!nanoparticles!to!proteins!for!alignment!of!images!from!cryo]electron!microscopy!(cryo]EM).!!We!proposed!to!form!nanoparticle]scFv!conjugates! for!attachment! to! specific! sites!on!proteins!of! interest.!!There!were! no!metal! nanoparticles! of! defined! size! and! surface! reactivity! available! at! the!time.!!We!developed!the!synthesis!of!large!gold!nanoparticles!and!solved!structures!by!X]ray!crystallography!and!aberration]corrected!EM.!!!!The!nanoparticles!could!be!reacted!with!single!scFvs!bearing!a!surface!cysteine!residue!and!then!quenched!to!prevent!further!reaction.!!Finally,!we!have!undertaken!two!applications!of!the! nanoparticle]scFvs:! ! extension! of! cryo]EM! to! near! atomic! resolution,! and! structure!determination!of!proteins!in!living!cells.! !

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45!

A*Twisting*Story:*How*A*Single*Gene*Twists*A*Snail*!Chirality!(left]right!(l]r)!asymmetry)!is!expressed!throughout!nature,!whether!microscopic!or!macroscopic,! and! whether! animate! or! inanimate.! In! the! biological! world,! chirality! is!observed!at!all! levels!of!hierarchy,!from!the!genetically]determined!macroscopic!individual!organisms!down!to!molecules!(only!D](deoxy)!ribose!in!nucleic!acids!and!only!L]amino!acids!in! proteins,! i.e.,! totally! homochiral).! The! maternal! inheritance! of! shell! coiling! and! its!correlation!with!the!spiral!blastomere!cleavage!in!gastropods!were!reported!in!the!late!19th!~!early!20th! century,!however,! the!underlining! causes!and!effects!had! remained!obscure.!We!have!revealed!that!the!initial!step!of!chiromorphogenesis!occurs!at!the!third!cleavage,!only!3!hours!after!the!first!cleavage!of!a!fertilized!egg!and!long!before!the!start!of!zygotic!gene!expression,!where!newly!formed!micromeres!rotate!levotropically!and!dextrotropically!with! respected! to! the! macromeres,! for! the! sinistral! and! dextral! snails,! respectively.! By!physically! twisting! the! micromeres! in! opposite! directions! at! this! stage,! we! could! create!healthy!mirror]image!snails,!and!the!chirality!of!their!offspring!reverted!back!to!the!original!as! expected.! Together! with! our! other! results,! we! could! prove! that! a! single! gene! locus!determines!body!handedness,!and!the!gene!dictates!the!cytoskeletal!dynamics!at!the!third!cleavage.! We! could! show! that! chirality! thus! established! is! transferred! to! the! cell]fate!determination! step! by! a! series! of! spiral! cleavages,! and! then,! an! organizer! macromere!activates!MAP!Kinase!signals!leading!to!the!asymmetric!zygotic!nodal!gene!expression!only!12! hours! after! the! first! cleavage.! Nodal! pathway! is! known! to! be! involved! in! asymmetric!morphogenesis!of!vertebrate,!though!at!much!later!stage!of!development.!Thus,!snails!are!ideal!model!animals!to!study!chiromorphogenesis!at!the!molecular!level.!!!There!are!still!many!questions!to!be!answered!regarding!the!first!and!the!subsequent!steps!of! chiromorphogenesis! as! well! as! the! link! between! asymmetry! of! animal! body! plan! and!homochiral! biomolecules.! We! have! been! trying! to! identify! the! single! handedness]determining!gene!in!snails!and!if!identified,!understanding!of!chirality!determination!at!the!molecular!level!shall!be!greatly!advanced!in!both!invertebrate!and!vertebrate.! !

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!!

47!

Advances*In*Biomaterials*And*Drug*Delivery*

Advanced! drug! delivery! systems! save! and! improve! the! lives! of! hundreds! of! millions! of!people! every! year.!! We! start! by! discussing! our! early! research! on! developing! the! first!controlled! release! systems! for! macromolecules! and! their! critical! role! in! the! isolation! of!angiogenesis!inhibitors!and!how!these!led!to!numerous!new!therapies.!!Nanoparticles!that!can!be!directly!targeted!to!cells!in!the!body!are!one!outgrowth!of!these!studies.!!In!addition,!for!many!years!scientists!used!off!the!shelf!household!materials!to!create!medical!devices;!e.g.,!artificial!hearts!were!made!from! ladies’!girdles;!materials!utilized! in!mattress!stuffing!were!used!for!breast!implants.!!

We!wished! to! change! that! paradigm! by! rationally! synthesizing! new!materials! for! specific!applications!from!first!principles.!!An!example!is!the!synthesis!of!new!degradable!materials!that! display! surface! erosion! such! as! polyanhydrides! that! have! led! to! new! treatments! for!brain!cancer.!!A!final!area!of!research!involves!the!combination!of!polymers!and!mammalian!cells!to!potentially!create!new!tissues!such!as!skin,!cartilage!or!even!spinal!cords.!!! !

!!

48!

Professor*JeanNMarie*Lehn*University!of!Strasbourg,!France!

!

Jean]Marie! Lehn! was! born! in! Rosheim,! France! in!1939.!In!1970!he!became!Professor!of!Chemistry!at!the! Université! Louis! Pasteur! in! Strasbourg! and!from!1979!to!2010!he!was!Professor!at!the!Collège!de!France!in!Paris.!He!is!presently!Professor!at!the!University! of! Strasbourg! Institute! for! Advanced!Study! (USIAS).! He! shared! the! Nobel! Prize! in!Chemistry! in!1987! for!his! studies!on! the! chemical!basis! of! “molecular! recognition”! (i.e.! the! way! in!which! a! receptor! molecule! recognizes! and!selectively! binds! a! substrate),! which! also! plays! a!fundamental!role!in!biological!processes.!!

Over!the!years!his!work!led!him!to!the!definition!of!a! new! field! of! chemistry,! which! he! has! proposed!calling!“supramolecular!chemistry”!as!it!deals!with!the!complex!entities! formed!by! the!association!of!two! or! more! chemical! species! held! together! by!non]covalent! intermolecular! forces,! whereas!molecular! chemistry! concerns! the! entities! constructed! from! atoms! linked! by! covalent!bonds.! Subsequently,! the! area! developed! into! the! chemistry! of! "self]organization"!processes!and!more!recently!towards!"adaptive!chemistry",!dynamic!networks!and!complex!systems.! Author! of! more! than! 950! scientific! publications,! Lehn! is! a! member! of! many!academies!and!institutions.!He!has!received!numerous!international!honours!and!awards.! !

!

!

49!

Perspectives*in*Chemistry*N*Steps*Towards*Complex*Matter**

*

Chemistry! is!progressively!unravelling! the!processes! that!underlie! the!evolution!of!matter!

towards!states!of!higher!complexity!and!the!emergence!of!novel!features!along!the!way.!It!

has!evolved!from!molecular!to!supramolecular!to!become!adaptive!by!way!of!constitutional!

dynamics.! Supramolecular! chemistry! is! intrinsically! a! dynamic! chemistry! in! view! of! the!

lability!of!the!interactions!connecting!the!molecular!components!of!a!supramolecular!entity!

and!the!resulting!ability!of!supramolecular!species!to!exchange!their!components.!The!same!

holds!for!molecular!chemistry!when!the!molecular!entity!contains!covalent!bonds!that!may!

form! and! break! reversibility,! so! as! to! allow! a! continuous! change! in! constitution! by!

reorganization! and! exchange! of! building! blocks.! These! features! define! a! constitutional!

dynamic! chemistry! (CDC)! covering! both! the! molecular! and! supramolecular! levels.! CDC!

introduces! a! paradigm! shift! with! respect! to! constitutionally! static! chemistry.! It! takes!

advantage!of!dynamic!diversity! to! allow!variation!and! selection!and!operates!on!dynamic!

constitutional! diversity! in! response! to! either! internal! or! external! factors! to! achieve!

adaptation.!!

Such! dynamic! systems! can! be! represented! by! dynamic! networks! that! define! the!

relationships!between!the!different!constituents!linked!through!component!exchange.!CDC!

opens!new!perspectives! in!materials!science!towards!adaptive!materials!and!technologies.!

The! implementation! of! these! concepts! points! to! the! emergence! of! adaptive! chemistry.!

Together!with!the!corresponding!fields!of!physics!and!biology,!chemistry!thus!plays!a!major!

role!in!the!progressive!elaboration!of!a!science!of!informed,!organized,!evolutive!matter,!a!

science#of!complex#matter.!

!

!

• Lehn,! J.]M.,! Supramolecular# Chemistry:# Concepts# and# Perspectives,! VCH! Weinheim,!

1995.!

• Lehn,! J.]M.,!Toward# complex#matter:# Supramolecular# chemistry# and# selfBorganization,!Proc.!Natl.!Acad.!Sci.!USA,!2002,!99,!4763.!

• Lehn,! J.]M.,!From#supramolecular# chemistry# towards# constitutional#dynamic# chemistry#and#adaptive#chemistry,!Chem.!Soc.!Rev.,!2007,!36,!151.!!!!!!!

• Lehn,!J.]M.,!Chapter!1,!in!Constitutional#Dynamic#Chemistry,!ed.!M.!Barboiu,!Topics#Curr.#Chem,!2012,!322,!1]32.!

• Lehn,!J.]M.,!Perspectives#in#Chemistry#–#Steps#towards#Complex#Matter,!!Angew.!Chem.!

Int.!Ed.,!2013,!52,!2836]2850.!! !

!!

50!

Professor*Richard*Lerner*The!Scripps!Research!Institute,!United!States!!Dr.! Richard! A.! Lerner’s! 40]year! scientific! career! is!significant! not! only! for! the! broad! scope! of! his!scientific! achievements,! but! for! his! leadership! as!President! of! The! Scripps! Research! Institute! (1986]2012),! the! country’s! largest! private,! non]profit!biomedical! research! organization.! ! The! scientific!accomplishments! for!which!he! is!perhaps!most!well!know! are! the! groundbreaking! work! of! converting!antibodies! into!enzymes,!permitting! the! catalysis!of!chemical!reactions!considered!impossible!to!achieve!by! classical! chemical! procedures! and! his!development! of! combinatorial! antibody! libraries!(simultaneously!with!Greg!Winter).!!A!member!of!the!National!Academy!of!Sciences!and!a!foreign!member!of!the!Royal!Swedish!Academy!of!Sciences,! Dr.! Lerner! graduated! from! Northwestern!University!and!Stanford!Medical!School.!!He!interned!at! Palo! Alto! Stanford! Hospital! and! received! postdoctoral! training! at! Scripps! Clinic! and!Research! Foundation.! ! Since! 1970! he! has! held! staff! appointments! at! Wistar! Institute! in!Philadelphia!and!at!The!Scripps!Research!Institute.!!!!!Dr.! Lerner! has! received! numerous! honorary! degrees,! prizes! and! awards,! including,! Parke!Davis!Award,!San!Marino!Prize,!Arthur!C.!Cope!Scholar!Award,!CIBA]GEIGY!Drew!Award! in!Biomedical! Research,! Humboldt! Research! Award,! Wolf! Prize! in! Chemistry,! California!Scientist! of! the! Year! Award,! Coley! Award! for! Distinguished! Research! in! Basic! and! Tumor!Immunology,! the!Windaus]Medial/Award,!President’s!Medal,!University!of!California,!Paul!Ehrlich]and! Ludwig! Darmstaedter! Prize,! Frankfurt,! Germany,! AAAS! Fellow,! DART/NYU!Biotechnology! Achievement! Award! in! Basic! Biotechnology,! New! York,! NY,! ! Distinguished!Visiting!Scientist!at! IBM!T.J.!Watson!Research!Center,!New!York,!Ulysses!Medal,!University!College! Dublin,! Belfield,! Dublin! Ireland,! Elected! Associate! Member! of! the! Exeter! Senior!Common! Room,! Exeter! College,! Oxford! University,! Oxford,! UK,! Courage! in! Innovation!Award,! Oxbridge! Biotech! and! Nature! Biotech,! London,! UK,! Prince! of! Asturias! Award! for!Scientific! and! Technical! Research,! Spain;! Honorary! Doctorate! of! Medicine,! Karolinska!Institute,! Honorary! Doctorate! ofScience! Award,! Technion]Israel! Institute! of! Technology,!Doctor!of!Science,!Northwestern!University,!Evanston,!IL,!Honorary!Doctorate!Degree,!Ben]Gurion!University!of!the!Negev,!Beer]Sheva,! Israel,!Honorary!Doctorate! in!Humane!Letters!from!Florida!Atlantic!University,!Boca!Raton,!Florida,!Honorary!Degree!of!Doctor!of!Science,!honoris! causa,!Oxford!University,!Oxford,!United! Kingdom.!Honorary!Degree! of!Doctor! of!Science,! honoris# causa,! University! College! Dublin,! Belfield,! Dublin! Ireland! and! Honorary!Degree!of!Doctor!of! Science,!University!of!Warwick,!Coventry,!United!Kingdom,!Honorary!Degree!of!Doctor!of!Science!Honoris!Causa,!The!Scripps!Research!Institute,!La!Jolla,!CA.! !

!!

51!

Combinatorial*Antibody*Libraries!!The!advent!of!combinatorial! libraries!allows!synthesis!of!an! immune!system!in!a!test!tube!without! the! use! of! live! animals.! The! system,! by! linking! recognition! and! replication,! uses!many!of!the!strategies!of!the!natural!immune!system!but!also!has!distinct!advantages.!First,!the! size!of! the! synthetic! repertoire! is!nowadays!at! least! three!orders!of!magnitude! larger!than! that! of! any! animal! including! man.! Most! importantly! the! central! issue! of! immune!tolerance! that! forbids!against!generation!of!antibodies! to! self! is!overcome,! thus,! allowing!one! to! generate! antibodies! to! any! self]protein.! This! is! important! because! all! but! one!therapeutic!antibody!in!clinical!use!today!is!an!antibody!to!self.!!!Recently,! new! formats! for! using! combinatorial! antibody! libraries! has! allowed! for! direct!autocrine!selection!of!agonist!antibodies!that!regulate!the!fate!of!normal!and!cancer!cells.!These! cellular! selections! can! proceed! at! a! rate! of! 20!million! events! an! hour!! Essentially,!antibody!libraries!have!converted!immunochemistry!from!a!stochastic!process!into!one!that!can!be!precisely!controlled!by!the!experimenter.! !

!!

52!

Professor*Michael*Levitt*Stanford!University,!United!States!!Born! in!South!Africa!1947,!Michael!Levitt!visited!London!aged!16! to!be!profoundly! influenced!by!John!Kendrew's!1944!BBC!TV!series!"The!Thread!of!Life".! !After!a!BSc! in!at!King’s!College!London!and!a!year!with!Prof.!Shneior!Lifson!and!his!PhD!student!Arieh!Warshel!at!the!Weizmann!Institute!in! Israel,! Levitt! joined! the! Laboratory! of!Molecular! (LMB),! Cambridge,! in! 1968.! His! PhD!thesis! on! Protein! Conformation! Analysis!described! use! of! classical! force]fields! and!introduced!energy!refinement.!!Levitt! went! back! to! Israel! as! an! EMBO! postdoc!with! Lifson.! Collaboration! then! with! Warshel!resulted! in! new! multi]scale! approaches! to!molecular!modeling:!!Coarse]grained!models!that!merge! atoms! to! allow! folding! simulation! and!hybrid! models! that! combine! classical! and!quantum!mechanics!to!explain!how!enzymes!works!by!electrostatic!strain.! ! In!1974,!Levitt!returned!to!LMB!for!three!years,!spent!two!years!with!Francis!Crick!at!Salk!and!seven!years!at!Weizmann,!before!moving!to!Structural!Biology!at!Stanford!from!1987.!!His! diverse! interests! have! included! RNA! &! DNA! modeling,! protein! folding! simulation,!classification! of! protein! folds! &! protein! geometry,! antibody! modeling,! x]ray! refinement,!antibody!humanization,!side]chain!geometry,!torsional!normal!mode,!molecular!dynamics!in!solution,! secondary! structure! prediction,! aromatic! hydrogen! bonds,! structure! databases,!and!mass!spectrometry.! !Current!postdocs!work!on!protein!evolution,! the!crystallographic!phase!problem!and!Cryo]EM!refinement.!!While!enjoying!membership!of!the!Royal!Society!and!the!National!Academy,!Levitt!remains!an! active! programmer,! a! craft! skill! of! which! he! is! particularly! proud.! ! His! post]prize!ambitions!are!two!fold!and! likely! inconsistent:! ! (1)! !Work!single]mindedly!as!he!did! in!the!mid]1970’s!on!hard!problems!and!(2)!Help!today’s!young!scientists!gain!the!recognition!and!independence!that!Levitt’s!generation!enjoyed.!!Married!in!1968!to!Rina,!an!active!artist,!they!have!three!children!and!a!rapidly! increasing!number!of!grandchildren,!all!of!whom!help!him!stay!more]or]less!normal.! !

!!

53!

Birth*&*Future*Of*Multiscale*Modeling*Of*Macromolecules*!The! development! multiscale! models! for! complex! chemical! systems! began! in! 1967! with!publications!by!Warshel! and! Levitt! recently! recognized!by! the!2013!Nobel! Committee! for!Chemistry.!!The!simplifications!used!then!at!the!dawn!of!the!age!of!computational!structural!biology!were!mandated!by! computers! that!were! almost! a! billion! times! less! cost]effective!than!those!we!use!today.!!!!These!same!multiscale!models!have!become!increasingly!popular! in!application!that!range!from! simulation! of! atomic! protein!motion,! to! protein! folding! and! explanation! of! enzyme!catalysis.!!In!this!talk!I!describe!the!origins!computational!structural!biology!and!then!go!on!to!show!some!of!the!most!exciting!current!and!future!applications.! !

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54!

Professor*David*Lilley*University!of!Dundee,!United!Kingdom!!David!Lilley!has!enjoyed!a!long!career!in!the!structure,!dynamics!and!activities!of!nucleic!acids,! both! DNA! and! RNA.! His! laboratory!uses! structural! (predominantly! X]ray!diffraction),! biophysical! (fluorescence,!especially! on! single! molecules)! and!biochemical! approaches,! combined! with! a!strongly!mechanistic!viewpoint.!!In! DNA,! Lilley! solved! the! structure! of! the!four]way! DNA! (Holliday)! junction,! and! has!made! extensive! studies! of! the! manner! of!their! interactions! and! recognition! by!junction]resolving! enzymes.! The! basic!recognition!processes!have!been!defined!in!bacterial!and!phage!enzymes,!but!now!the!work! has! been! extended! to! include! the!eukaryotic!enzymes!GEN1!and!SLX1/SLX4.!!In!RNA!Lilley!has! long!advocated! the!view! that!complex! structure!can!be! reduced! to! rigid!helical! elements! jointed!by! junctions! that!determine! the! trajectory.! In! the! last! decade!he!has!made!detailed!studies!of!the!kink]turn!element!to!the!point!where!this!is!now!arguable!the!best]understood!such!motif.!He!has!generated!a!set!of!rules!for!!kink]turn!folding!that!have!strong!predictive!power,!and!can!be!applied!to!new!RNA!sequences!as!they!emerge.!!In! additional! to! structural! elements,! Lilley! has! made! detailed! mechanistic! and! structural!studies! of! RNA! catalysis,! particularly! seeking! chemical! explanation! of! the! origins! of! these!catalysts.!He!has!particularly!characterized!the!mechanisms!of!general!acid]base!catalysis!in!the!hairpin,!VS,!hammerhead!and!most!recently!the!twister!ribozyme.!!Along! the! way,! Lilley! has! been! involved! in! the! development! of! fluorescence! resonance!energy!transfer!(FRET)!as!a!structural!tool!in!nucleic!acids.!His!1989!paper!in!Nature!studying!the!structure!of!the!four]way!DNA!junction!was!the!first!of!the!modern!era!of!FRET.!Since!then! this! has! been! applied! extensively! in! single]molecule! studies! and!most! recently! Lilley!has!developed!the!analysis!of!the!k2!parameter!to!provide!orientational!information,!and!as!an!additional!benefit,!improved!distance!information.!!David! Lilley! (as!��)! has! strong! links! with! China.! He! is! a! visiting! professor! at! the!University! of! Xiamen! in! Fujian,! holds! joint! grants! in! collaboration! with! Shanghai! Fudan!University!and!regularly!consults!for!AB!Life!in!Wuhan,!Hubei!province.! !

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56!

Professor*Susan*Lindquist*Massachusetts!Institute!of!Technology,!United!States!

!

Susan! Lindquist! is! a! world! leader! in! the! study! of!protein! folding.! Her! pioneering! work! has!demonstrated! that! alternative! protein! conformations!have! profound! and! unexpected! effects! in! fields! as!wide! ranging! as! human! disease,! evolution,! and!biomaterials.! !Her!work!on!yeast!prions!has!provided!evidence!for!a!mechanism!of!protein]only! inheritance!and! contributed! to! a! structural! understanding! of!amyloid!fiber!formation.!!She!has!shown!in!a!variety!of!model! systems! that! molecular! chaperones! can!influence!the!expression!and!evolution!of!new!traits!by!chaperoning! the! folding! of! key! players! in! signal!transduction! pathways.!Most! recently,! her! group! has!developed! new! platforms! for! dissecting! the! protein]folding! problems! that! drive! neurodegenerative!diseases,!with!the!aim!of!discovering!new!therapeutic!strategies! based! on! stopping! the! precipitating! causes!of!such!protein]folding!disorders.!

Susan! Lindquist! is! a! Member! and! former! Director!(2001]2004)! of! the! Whitehead! Institute! for! Biomedical! Research,! an! Investigator! of! the!Howard!Hughes!Medical!Institute!and!a!Professor!of!Biology!at!MIT.!Previously!she!was!the!Albert! D.! Lasker! Professor! of! Medical! Sciences! (from! 1999]2001),! and! a! member! of! the!faculty! in! the!Department!of!Molecular!Biology,!University!of!Chicago.! ! Lindquist! received!her! undergraduate! degree! in! Microbiology! from! the! University! of! Illinois,! and! a! PhD! in!Biology! from! Harvard! University.! She! co]founded! FoldRx,! a! biotech! company! developing!drug!therapies!for!diseases!of!protein!misfolding!and!amyloidosis,!and!recently!co]founded!Yumanity,! a! biotech! company! identifying! and! and! developing! new! therapies! for!neurodegenerative!diseases!caused!by!protein!misfolding.!She!is!a!member!of!the!Board!of!Directors!of!Johnson!&!Johnson.!Her!honors!include!membership!in!the!National!Academy!of!Sciences,!the!American!Academy!of!Arts!and!Science,!the!American!Philosophical!Society!and! the! Institute! of!Medicine.! She! has! been! awarded! the! Dickson! Prize! in!Medicine,! the!Otto]Warburg!Prize,!the!Genetics!Society!of!America!Medal,!the!FASEB!Excellence!in!Science!Award,! the! Max! Delbrück! Medal,! the! Mendel! Medal,! the! E.B.! Wilson! Medal,! a! Vallee!Professorship!and!the!Vanderbilt!Prize.!In!2009,!she!was!the!recipient!of!the!National!Medal!of!Science.! !

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57!

Lamarck*Was*Right:*Better*Living*Through*Chemistry*

!

Prions!live!in!infamy!as!the!infectious!agent!in!!“mad!cow!disease”.!!Far!more!exciting!is!their!ability!to!act!as!protein]based!elements!for!inheritance.!Prion!proteins!change!their!shapes!and!template!those!changes!to!other!proteins!of!the!same!type.!The!associated!change! in!protein! function! is! passed! to! progeny! cells! for! hundreds! of! generations.! Reed! Wickner!suggested! such! a! mechanism! based! upon! puzzling! inheritance! patterns! in! yeast.! My! lab!discovered! the! two! key! biochemical! mechanisms:! ! first,! prions! arise! when! a! natively!unfolded! protein! adopts! an! amyloid! conformation.! This! “information! template”! changes!protein! function! in! a! self]templating!way.! Second,! the! template! is! severed!by! the!protein!remodeling! factor!Hsp104,! allowing! inheritance!by!daughter! cells.! In! yeast! alone,! over! 30!proteins!switch!states!and!create!new!biological!traits!in!this!way.!!

Prions! are! considered! by! some! to! be! simply! diseases! of! yeast! or! “laboratory! artifacts”.!Others,!starting!with!my!lab,!view!them!as!remarkably!valuable!mechanisms!for!generating!heritable! diversity! and! fueling! the! pace! of! evolution.! ! As! prion! proteins! often! sit! at! key!points! in! regulatory!networks,! their! changes! in! shape!and! function!create!a!wide!array!of!complex!traits.!!Of!course,!these!are!sometimes!detrimental,!but!often!promote!survival,!at!least!in!the!laboratory.!!But!are!prions!serving!such!roles!in!nature?!!We!examined!700!wild!yeast! strains,! from! diverse! environments! all! over! the! world;! >250! contained! prions! that!conferred!fundamentally! important!biological!traits.!The!interface!between!protein!folding!and!environmental!stress! increases!prion!switching!rates.!Thus,!prions!act!as!sophisticated!‘bet]hedging’!devices,!providing!a!reservoir!of!biological!diversity!when!it!is!most!needed.!

Most! recently!we! have! extended! the! boundaries! of! the! prion!world.!We! find! that! prions!have! the! capacity! to! transform! the! dynamics! of! microbial! communities! and! provide! a!biological! example! of! “better! living! through! chemistry”.! Bacteria! in! the! bacteria]yeast!community! secrete! a! chemical! compound! that! induces! a! prion]based! heritable! change! in!metabolism! in! yeast! growing! in! their! environment! resulting! in! enhanced! growth! of! both!organisms.!Thus,!this!prion!provides!the!most!compelling!and!simple!example!of!Lamarkian!inheritance!yet.! !

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Professor*Yahli*Lorch*Stanford!University,!United!States!!Dr.! Yahli! Lorch! is! Associate! Professor!(Research)! in! the!Department!of!Structural!Biology!at!the!Stanford!University!School!of!Medicine.!!!She!served!in!the!Israel!Defense!Forces! from!1973]75.! !She!received!a!B.Sc.!in! Biology! from! the! Hebrew! University! in!1978! and! a! Ph.D.! in! Genetics! from! the!Hebrew!University!in!1983.!!!!She! began! her! research! career! with!genomic!and!proteomic!analyses!of!the!two!types!of!Theiler’s!murine!virus,!one!causing!rapidly! fatal! encephalitis! and! the! other! a!chronic! demyelinating! disease! similar! to!Multiple!Sclerosis!in!humans.!!She!turned!to!the!molecular!basis!of!gene!expression!with!the! demonstration! that! a! synthetic!oligonucleotide! containing! an! activator!protein]binding! site! serves! as! a! transcriptional! enhancer.! ! In! 1987,! she! showed! that! the!nucleosome,!previously!viewed!as!a!basis!for!chromosome!structure,!plays!a!key!functional!role,!serving!as!a!general!gene!repressor.!!!In!1996,!she!and!co]workers!discovered!the!RSC!chromatin]remodeling! complex,! which! relieves! repression! by! the! nucleosome.! ! In!subsequent! studies,! she! identified! two! modes! of! remodeling! by! RSC! and! elucidated! the!underlying!mechanisms.!! !

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59!

Chromatin*Remodeling*!The!nucleosome!is!the!basic!unit!of!chromosome!organization.!!It!comprises!146!base!pairs!of! DNA! wrapped! around! a! histone! octamer.! ! It! was! once! thought! to! serve! primarily! a!structural!role,!in!the!compaction!of!DNA.!!We!found,!however,!that!the!nucleosome!is!also!crucial! for!gene! regulation;! ! it! serves!as!a!general!gene! repressor.! ! The!question!arises!of!how! repression! is! relieved! for! the! transcription! of! genes! required! for! cell! growth! and!development.!!The!answer!lies!in!the!activities!of!chromatin]remodeling!complexes.!!!We! discovered! an! 18]protein! chromatin! remodeling! complex,! termed! RSC,! with! two!activities!essential! for! transcription.! !RSC!catalyzes! the! sliding!of!nucleosomes!along!DNA,!and!the!disruption!of!nucleosomes!with!the!eviction!of!histone!octamers!from!DNA.!!These!two! activities! account! for! the! distinctive! features! of! transcriptionally! active! genes.! ! RSC!evicts!an!octamer!in!an!ATP]dependent!manner!to!create!a!nucleosome]free!region!in!front!of! a! gene,! exposing! sites! in! the! DNA! for! binding! both! transcription! factors! and!transcriptional! regulatory! proteins.! ! RSC! also! forms! a! complex! with! a! nucleosome! in! the!absence!of!ATP!in!which!DNA!is!released!from!the!surface!of!the!nucleosome.!This!activity!of!RSC!has!been!implicated!in!the!exposure!of!start!sites!for!transcription.!!RSC!therefore!plays!multiple!roles!in!the!relief!of!repression!by!the!nucleosome.! !

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Professor*Andrew*McCammon*University!of!California,!San!Diego,!United!States!!J.! Andrew! McCammon! is! a! Distinguished!Professor! of! Chemistry! &! Biochemistry! and! of!Pharmacology! at! UCSD,! and! an! Investigator! in!HHMI.! After! 16! years! in! Houston,! he!moved! to!UCSD! in! 1995.! ! In! the! 1980’s,! he! guided! the!establishment!of!computer]aided!drug!discovery!in!Agouron!Pharmaceuticals!(now!Pfizer’s!La!Jolla!Laboratories),! contributing! to! the! development!of! the! HIV]1! protease! inhibitor,! nelfinavir!(Viracept).!!!!His! group’s! studies! of! HIV]1! integrase! flexibility!subsequently! aided! the! discovery! of! raltegravir!(Isentress)!by!Merck!&!Co.!He! is!a!Fellow!of! the!American! Academy! of! Arts! and! Sciences! and! a!Member!of!the!US!National!Academy!of!Sciences.! !

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61!

ComputerNaided*Drug*Discovery**The!selective!character!of!the!binding!and!reactivity!of!key!biological!molecules!is!essential!for!life.!!Properly!understood,!such!selectivity!can!be!exploited!in!the!design!of!drugs,!novel!antibodies! or! enzymes,! sensors,! or! a! host! of! other! materials! or! devices.! ! This! talk! will!provide! a! brief! overview! of! how! computer! simulations! can! be! used! quantitatively! to!interpret!the!selectivity!of!molecular!behavior.!!Particular!emphasis!will!be!placed!on!proper!accounting!of!the!flexibility!of!the!receptor!in!the!design!of! ligands.! !The!Relaxed!Complex!Scheme!for!sampling!receptor!conformations!played!a!key!role!in!the!discovery!of!the!first!FDA]approved! inhibitor!of!HIV! integrase,! and! it! has! led! to!new!antibiotic! leads! and!other!promising!compounds.!!!!The! Accelerated! Molecular! Dynamics! method! increases! the! power! of! such! studies,! and!opens! the!way! to! the!discovery!of! ligands!by!direct! simulation!of! their!binding!processes.!Very! recently,! novel! constant]pH! molecular! dynamics! simulation! methods! have! proven!useful! in! the! calculation! of! the! pH]dependent! free! energy! of! binding! of! drug! leads.! The!potential! of! new! generations! of! computing! hardware! and! methodology! to! dramatically!transform!this!area!of!work!will!be!emphasized.!Images!and!animations!related!to!this!work!can!be!found!at!the!website!http://mccammon.ucsd.edu/.! !

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Professor*Josef*Michl*University! of! Colorado! at! Boulder,! United! States,! and! Institute! of! Organic! Chemistry! and!Biochemistry!ASCR,!Czech!Republic!

!

Born! in! 1939! in! Prague,! Czechoslovakia.!!M.S.!in!Chemistry!in!1961!with!V.!Horák!and!P.! Zuman! at! Charles! University,! Ph.D.! in!1965!with!R.!Zahradník!at!the!Czechoslovak!Academy! of! Sciences,! all! in! Prague.! ! Left!Czechoslovakia! in! 1968,! did! postdoctoral!work!with!R.!S.!Becker!at! the!University!of!Houston,!M.!J.!S.!Dewar!at!the!University!of!Texas! at! Austin,! J.! Linderberg! at! Aarhus!University,!Denmark,!and!F.!E.!Harris!at!the!University! of! Utah,! where! he! stayed! and!became!a!full!professor!in!1975!and!served!as!chairman!in!1979]1984.!!In!1986]1990!he!held!the!M.!K.!Collie]Welch!Regents!Chair!in!Chemistry! at! the! University! of! Texas! at!Austin! and! subsequently! moved! to! the!University!of!Colorado,!Boulder,!CO,!where!he! is! Professor! of! Chemistry! presently.!!Since! 2006,! he! has! had! an! appointment! in! the! Institute! of! Organic! Chemistry! and!Biochemistry!of!Czech!Academy!of!Sciences!in!Prague,!Czech!Republic.!

He!has!held!numerous!visiting!professorships!and!named!lectureships,!delivered!hundreds!of! invited! lectures! at! institutions! and! conferences,! has! served! on!many! professional! and!editorial!boards,!advisory!councils,!and!committees,!and!has!organized!several!international!conferences.! ! He! has! been! a! Sloan,! a! Guggenheim,! a! Fulbright,! a! University! of! Colorado!Faculty,! and! ACS! Fellow,! has! won! the! Cope! Scholar,! Utah! Section,! Kosolapoff! and! James!Flack! Norris! ACS! Awards,! the! A.! v.! Humboldt! Senior! U.S.! Scientist,! Japan! Society! for!Promotion! of! Science,! Inter]American! Photochemical! Society,! Hammond,! Boron! in! the!Americas,!and!Wichterle!Awards,!the!Schrödinger!and!Porter!Medals,!the!J.!Heyrovský!and!Charles! University! Gold! Medals,! the! Patria! award! from! the! Czech! government,! and! the!Marinus! Smith! Award! of! the! University! of! Colorado.! ! He! has! honorary! degrees! from!Georgetown!University,! the! University! of! Pardubice! and! the!Masaryk! University.! ! He! is! a!member!of! the!US!National!Academy!of!Sciences,!and!the!American!Academy!of!Arts!and!Sciences,!and!an!honorary!member!of!the!Czech!Learned!Society.!!He!is!the!President!of!the!International! Academy! of! Quantum! Molecular! Science.! ! He! was! the! editor]in]chief! of!Chemical# Reviews! in! 1984]2014,! has! co]authored! five! books! on! photochemistry! and!polarization!spectroscopy,!and!over!six!hundred!scientific!papers.! !

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63!

Unconventional*Solar*Energy*–*Singlet*Fission!

!Singlet!fission!is!a!process!that!generates!two!triplet!excitations!from!one!singlet!excitation.!!It!offers!the!potential!to!overcome!the!one]third!Shockley]Queisser! limit! in!single]junction!solar!cells!and!to! increase!to!nearly!one]half! the!theoretical!efficiency!of! inexpensive!cells!with! two!sensitizer! layers!but!no!current!matching! requirement.! !The!difficulty! is! that! the!number!of!materials!known!to!perform!singlet!fission!efficiently!is!extremely!small!and!their!structures! are! mostly! quite! similar.! ! We! shall! provide! an! overview! of! our! efforts! to! use!simple!quantum!chemical!models!to!formulate!structural!design!rules!for!different!types!of!materials!that!would!perform!singlet!fission!efficiently.!!We!are!interested!in!chromophores!that!are!either!much!smaller!than!the!few!already!known,!for!easier!high]level!treatment,!or!much!sturdier,!for!practical!utility.!!We!address!two!issues,!(i)!choice!of!chromophores,!and!(ii)!choice!of!the!spatial!relation!between!them.!!!!Of! the! two! classes! of! chromophores! that! we! have! identified! as! promising,! alternant!hydrocarbons!and!biradicaloids,!we!have!focused!on!the!latter!as!structurally!more!diverse,!and!shall!describe!several!new!candidates.!As!for!the!spatial!relation,!using!a!combination!of!two! ethylenes! and! performing! a! fairly! complete! numerical! search! in! the! six]dimensional!space!of! their!mutual!disposition,! the!best!choice! found!so! far! is!a! slip]stacked!geometry,!with! the! slip! in! the! direction! of! the! HOMO]LUMO! transition! moment.! ! A! further!simplification!of!the!model! leads!to!a! formulation!of!a!structurally!predictive!formula!that!requires!only! the!knowledge!of! the! coefficients!of! the!Hueckel! frontier!molecular!orbitals!and!of!the!overlaps!of!the!atomic!orbitals!on!the!two!chromophores.!! !

!!

64!

Professor*William*Moerner*Stanford!University,!United!States!!W.! E.! (William! Esco)!Moerner,! the!Harry! S.!Mosher!Professor!of!Chemistry!and!Professor,!by!courtesy,!of!Applied! Physics! at! Stanford! University,! conducts!research! in!physical! chemistry!and!chemical!physics!of! single! molecules,!single]molecule!biophysics,!super]resolution!imaging! and!tracking! in!cells,!and!trapping!of!single!molecules! in!solution.! His! interests! span! methods! of! precise!quantitation! of! single]! molecule! properties,! to!strategies! for!three]dimensional!imaging! and!tracking!of!single!molecules,!to!applications!of!single]molecule!measurements! to! understand! biological!processes! in! cells,! to! observations! of! the!photodynamics!of!single!photosynthetic!proteins!and!enzymes.!!!He! has! been! elected! Fellow/Member! of! the! NAS,!American!Academy!of!Arts!and!Sciences,!AAAS,!ACS,!APS,! and! OSA.! Major! awards! include! the! Earle! K.!Plyler!Prize! for!Molecular!Spectroscopy,! the! Irving!Langmuir!Prize! in!Chemical!Physics,! the!Pittsburgh! Spectroscopy! Award,! the! Peter! Debye! Award! in! Physical! Chemistry,! the! Wolf!Prize!in!Chemistry,!and!the!2014!Nobel!Prize!in!Chemistry.!! !

!!

65!

!SingleNMolecule* Spectroscopy,* Blinking,* and* Photocontrol:* Foundations* for* SuperNResolution*Microscopy*#More!than!25!years!ago,! low!temperature!experiments!aimed!at!establishing!the!ultimate!limits! to! optical! storage! in! solids! led! to! the! first! optical! detection! and! spectroscopy! of! a!single!molecule!in!the!condensed!phase.!!At!this!unexplored!ultimate!limit,!many!surprises!occurred!where! single!molecules! showed! both! spontaneous! changes! (blinking)! and! light]driven!control!of!emission,!properties!that!were!also!observed!in!1997!at!room!temperature!with!single!green! fluorescent!protein!variants.! In!2006,!PALM!and!subsequent!approaches!showed!that!the!optical!diffraction!limit!of!~200!nm!can!be!circumvented!to!achieve!super]resolution! fluorescence!microscopy,! or! nanoscopy,! with! relatively! nonperturbative! visible!light.! ! Essential! to! this! is! the! combination! of! single]molecule! fluorescence! imaging! with!active! control! of! the! emitting! concentration! and! sequential! localization! of! single!fluorophores!decorating!a!structure.!!!!Super]resolution!microscopy! has! opened! up! a! new! frontier! in!which! biological! structures!and!behavior!can!be!observed! in! live!cells!with!resolutions!down!to!20]40!nm!and!below.!!Examples! range! from! protein! superstructures! in! bacteria! to! bands! in! actin! filaments! to!details! of! the! shapes! of! amyloid! fibrils! and! much! more.! ! Current! methods! development!research!addresses!ways!to!extract!more!information!from!each!single!molecule!such!as!3D!position!and!orientation,!in!thick!cells.!Still,!it!is!worth!noting!that!in!spite!of!all!the!focus!on!super]resolution,! even! in! the! “conventional”! single]molecule! tracking! regime! where! the!motions! of! individual! biomolecules! are! recorded! in! solution! or! in! cells! rather! than! the!shapes!of!extended!structures,!much!can!still!be!learned!about!biological!processes.!!! !

!!

66!

Professor*Shuji*Nakamura*University!of!California!Santa!Barbara,!United!States!!Dr.! Shuji! Nakamura! obtained! B.E.,! M.S.,! and! Ph.D.!degrees!in!Electrical!Engineering!from!the!University!of!Tokushima.!!He! joined!Nichia! Chemical! Industries! Ltd.!in! 1979.! In! 1989,! he! started! researching! blue! LEDs!using!group]III!nitride!materials.!Nakamura!developed!the! first! III]nitride]based! blue/green! LEDs! and! III]nitride]based!violet!laser!diodes.!!!Dr.!Nakamura!joined!the!University!of!California,!Santa!Barbara!in!1999.!He!is!currently!the!Research!Director!of!the!Solid!State!Lighting!&!Energy!Electronics!Center!and! The! Cree! Professor! in! Solid! State! Lighting! and!Display.! His! research! includes! MOCVD,! UVPE,! and!growth!and!device!fabrication!of!gallium!nitride!(GaN)!light]emitters.! He! received! the! 2006! Millennium!Technology! Prize! for! his! invention! of! revolutionary!new! energy]saving! light! sources!and! the! 2014! Nobel!Laureate! in!Physics! for! the! invention!of! efficient!blue!LEDs,! which! have! enabled! bright! and! energy]saving!white!light!sources.!Dr.!Nakamura!is!also!the!co]founder!of!Soraa!Inc.!! !

!!

67!

!Background*Story*and*Development*of*High*Efficiency*Blue*GaN*LEDs*and*Laser*Diodes*!The! development! of! high! brightness! blue! LEDs! and! blue! laser! diodes! required! many!breakthroughs!of!III]Nitride!growth,!p]type!conductivity!control!and!device!structures!using!InGaN/GaN! double! heterostructures.! First,! the! speaker! will! discuss! the! history! and!background!story!of!the!key!scientific! issues!solved! in!order!to!realize!high!efficiency!solid!state! lighting.! ! The! fundamental! discovery! of! high! quality! p]type! doping! by! removing!hydrogen!passivation,!and! the! role!of! the! InGaN/GaN!double!heterostructure! in!achieving!high! brightness! blue! LEDs! and! Laser!Diodes!will! be! described.! ! Next! the! speaker!will! talk!about! the! latest! results! of! nonpolar! and! semipolar! emitting! devices! at! the! University! of!California!at!Santa!Barbara.!In!particular,!solving!both!current!“droop”!and!thermal!“droop”!has!been! identified!as!key! roadblocks! to! cost! reduction!and! further! improvements! in! LED!Lighting.!New!LED!structures!grown!by!MOCVD!on!semipolar!orientations!of!bulk!GaN!have!shown! remarkable! efficiencies! with! EQE! greater! than! 50%! at! high! current! densities!(400A/cm2)! and! improved! thermal! droop! characteristics.! The! future! uses! of! GaN! laser! in!display!and!lighting!will!be!introduced.! !

!

!

68!

Professor*Dinshaw*Patel*Memorial!Sloan!Kettering!Cancer!Center,!United!States!

!

Dr.!Dinshaw!J.!Patel!received!his!PhD!in!Chemistry!

from! New! York! University! in! 1968.! He! was! a!

Distinguished!Member! of! Technical! Staff! at! AT&T!

Bell! Laboratories! for! 17! years,! a! Professor! of!

Biochemistry! and! Molecular! Biophysics! at!

Columbia!University! for! 8! years,! before! taking! up!

his! current! appointment! at! the! Memorial! Sloan]

Kettering! Cancer! Center! in! 1992! as! Abby!

Rockefeller! Mauze! Chair! in! Experimental!

Therapeutics.! He! is! a!Member! of! the!US!National!

Academy! of! Sciences! and! American! Academy! of!

Arts!and!Sciences.!

!

The! structural! biology! research! of! Dr.! Patel! has!

focused!on!combined!structure]function!studies!of!

RNA! folding! and! catalysis,! RNA! silencing,! histone!

and! DNA! modification]mediated! epigenetic!

regulation,! lipid! transfer! proteins! and! pattern!

recognition! receptors! of! infection! that! trigger! an!

immune!response.!

!

His! laboratory! has! contributed! to! our! structural! understanding! of! riboswitches! and!

ribozymes! involved! in! gene! regulation,! thereby! defining! the! architecture! of! higher]order!

RNA! scaffolds,! the! evolution! of! ligand]binding! pockets! and! mechanisms! underlying! RNA]

mediated!catalysis.!His! laboratory!has!made!groundbreaking!contributions! to!protein]RNA!

recognition!events!in!the!RNA!silencing!pathway.!The!focus!has!been!on!the!enzymes!Dicer!

and!Argonaute! and! their! complexes!with!RNA,! leading! to! a!mechanistic! understanding!of!

nucleation,! propagation! and! cleavage! steps! associated!with! the!Argonaute]mediated!RNA!

silencing! pathway.! His! laboratory! has! also! been! interested! in! the! structural! biology! of!

readers,!writers!and!erasers!of!histone!and!cytosine!methylation!marks.!Structural!studies!

have! identified! the! principles! underlying! readout! specificity! of! histone! marks,! as! well! as!

elucidated! how! a! combination! of! active! and! autoinhibitory! mechanisms! ensure! the! high!

fidelity! of!maintenance! DNA!methylation.! ! His! laboratory! has! contributed! to! our! current!

understanding! of! how! lipid! transfer! proteins! acquire! and! release! glycosphingolipids! and!

phospholipids!during!lipid!intermembrane!transfer!and!presentation!processes.!!

!

Recently,! his! laboratory! has! studied! metazoan! sensors! of! dsDNA! in! the! cytoplasm! that!

trigger! the! innate! immune! response.! Structural! studies! have! highlighted! the! principles!

underlying!generation!of!the!metazoan!second!messenger!cyclic!GAMP!produced!by!DNA]

activated! cyclic! GMP]AMP! synthase,! the! activation! of! the! adaptor! STING! by! cGAMP! and!

targeting!of!STING!by!anti]viral!small!molecules.!! !

!!

69!

StructureNFunction*Studies*of*Cytosolic*DNA*Sensors*Governing*the*Interferon*Response!!The!lecture!will!outline!recent!results!that!have!emerged!from!a!collaborative!program!(1)!on!the!metazoan!cytoplasmic!dsDNA!sensor!cyclic!GMP]AMP!synthase!(cGAS).!These!studies!address!the!role!of!cyclic!GMP]AMP!(cGAMP)!as!a!metazoan!second!messenger!triggering!an!interferon! response,! with! the! cGAMP! linkage! isomer! c[G(2’,5’)pA(3’,5’)p]! generated! from!GTP!and!ATP!by!DNA]activated!cGAS.!Our!structural]functional!studies!will!highlight!how!a!single! catalytic! pocket! can! generate! c[G(2’,5’)pA(3’,5’)p]! through! a! step]wise! cyclization!process,! thereby! identifying!and!structurally/chemically!characterizing!a! founding!member!of!a!new!family!of!metazoan!cyclic!hetero!dinucleotide!second!messengers!(2).!The!lecture!will! also! outline! structure]function! studies! of! the! activation! of! signaling! protein! STING!(stimulator!of!interferon!genes)!by!c[G(2’,5’)pA(3’,5’)p],!its!linkage!isomers!and!drug!DMXAA!(3,!4).!!1. Laboratories! of! Thomas! Tuschl! (Rockefeller! University,! in# vitro! biochemical! studies),!

Winfried! Barchet! and! Gunther! Hartmann! (University! Hospital,! Bonn,! in# vivo! cellular!studies),! Liang! Deng! (Memorial! Sloan]Kettering! Cancer! Center,! innate! signaling!mechanisms),! Roger! Jones! (Rutgers! University,! synthetic! chemistry)! and! our! group!(Memorial!Sloan]Kettering!Cancer!Center,!structural!biology).!

2. Gao,!P.!et!al.!and!Patel,!D.!J.! (2013).!Cyclic![G(2’,5’)pA(3’,5’)p]! is!the!metazoan!second!messenger!produced!by!DNA]activated!cyclic!GMP]AMP!synthase.!Cell!153,!1094]1107.!

3. Gao,!P.! et! al.! and!Patel,!D.J.! (2013)! Structure]function!analysis!of! STING!activation!by!c[G(2’,5’)pA(3’,5’)p]!and!targeting!by!DMXAA.!Cell#154,!748]762.!

4. Gao,!P.!et!al.!and!Patel,!D.!J.!(2014).!Binding!pocket!and!lid!region!substituents!render!human!STING!sensitive!to!mouse]selective!drug!DMXAA.!Cell!Reports!8,!1668]1676.! !

!

!

70!

Professor*Dina*Petranovic*Chalmers!University!of!Technology,!Sweden!

!

Associate!Professor!Dina!Petranovic!was!born! in!

Zagreb,! Croatia,! where! she! studied! Molecular!

Biology.! During! her! Bsc! and! Msc! projects! she!

worked!with!maze!and!yeast!mitochondrial!seryl]

tRNA! synthetase.! She! holds! a! PhD! in!Molecular!

Microbiology!from!Université!Paris!XI,!where!she!

graduated! in! 2004!with! summa# cum# laude.! Her!PhD! project! was! focused! on! transcriptional!

regulation!in!Lactococcus#lactis,!mediated!by!the!

transcriptional!regulator!CodY.!!

!

After! her! thesis! Prof! Petranovic! went! for! two!

postdocs! in! Copenhagen,! Denmark,! where! she!

worked! on! L.# lactis! and! Bacillus# subtilis! signal!transduction! mediated! by! tyrosine!

phosphorylation,! and! on! yeast! systems! biology.!

In! 2008! Dina! moved! to! Chalmers! University! of!

Technology!and!established!a!group!on!cell!aging!

and!death!research.!Her!work!has!been!published!in!44!international!peer]reviewed!articles.!

In!2013!Dina!was!tenured!at!Chalmers!and!that!same!year!she!also!received!The!Chalmers!

Award!as!the!best!teacher.!!

!

Dina!has!extensive!academic!experience!as!mentor!and!supervisor,!reviewer,!editor,!expert!

evaluator! and! scientific! manager.! Since2012! she! is! the! CEO! Global! of! the! Molecular!

Frontiers! Foundation! that! is! established! under! the! Royal! Swedish! Academy! of! Sciences!

(KVA).!!

!

For! a! more! complete! CV! please! check! the! Petranovic! Lab! page:!

http://www.sysbio.se/Lab_Petranovic/lab_dina.html!! !

!!

71!

Mutant*Ubiquitin*(UBB+1)*and*Alzheimer’s*Disease*(AD)*!The! ubiquitin]proteasome! system! (UPS)! is! a! principal! proteolytic! pathway! which! plays! a!major! role! in! a! variety! of! fundamental! cellular! processes! (Upadhya! et! a.,! 2006).!Dysfunctional!UPS!has!been!involved!in!neurodegenerative!disorders,!in!which!proteasome!function!has!been!shown!to!be!decreased!(de!Vrij!et!al.,!2004).!UBB+1!(ubiquitin!B!protein+1)!is! a! mutant! of! the! ubiquitin! B! protein! which! accumulates! in! an! age]dependent! manner,!occurs!as!a!result!of!molecular!misreading,!and!appears!to!contribute!to!the!neuropathology!in!Alzheimer’s!disease!(AD)!(Dennissen!et!al.,!2010).!!In! order! to! investigate! the! intracellular! mechanisms,! we! are! interested! in! understanding!how! the! level! of! UBB+1! is! involved! in! the! abnormal! activity! of! UPS,! particularly! under!conditions!of!aging!as!this!is!the!highest!risk!factor!for!neurodegenerative!disorders!such!as!AD.!We!use!yeast!as!a!model!Eukaryal!system!and!for!study!of!proteins!involved!in!AD,!and!their!influence!on!the!cell.!!!In! this! project! we! will! use! a! broad! range! of! techniques! such! as! genetic! engineering,!apoptosis! and! viability! assays,! mitochondrial! integrity! tests,! activation! of! caspases!measurements,! ROS!quantification,! ER]stress! induction,! proteasome!activity! and! genome]wide!transcription!response.!!!Our! goal! is! to! understand! the! functions! of! UBB+1! including! characterizing! its! molecular!mechanisms!of!action!and!genetic!determinants!(as!found!in!yeast)!and!studying! its!effect!on!cellular!pathways!related!to!aging!and!neurodegeneration!on!the!cellular!level!(neuronal!cultures)! as! well! as! on! the! organism! level! in! an! AD! animal! model! (fruit! fly).! Such!understanding!may!reveal!important!links!between!UBB+1!expression!and!protein!misfolding!and!aggregation!that!are!the!major!pathological!hallmarks!of!AD,!and!has!the!potential!of!providing!new!targets!for!future!therapeutic!intervention.! !

!!

72!

Professor*Barry*Sharpless*The!Scripps!Research!Institute,!United!States!

!

K.! Barry! Sharpless! is! best! known! among!synthetic! chemists! for! discovering! and!developing! many! widely! used! catalytic!oxidation! processes,! especially! the! work! for!which!he!received!a!Nobel!Prize!in!2001,!the!first! general! methods! for!asymmetric!oxidation—the!Sharpless!reactions!for!asymmetric!epoxidation!(1980),!dihydroxylation! (1988)! ,! and!aminohydroxylation!(1996).!

Among! a! newer! generation! of! scientists!representing! the! entire! chemical! spectrum,!from! chemical! engineering! and! materials! to!chemical!biology,!Sharpless!is!known!for!click!chemistry,!a!term!he!coined!in!1998.!Inspired!by! the! complexity! nature! achieves! from! a!handful! of! building! blocks,! Sharpless! started!actively! looking! in! the!mid]90s!for! a! way! to!discover! new! chemical! connectivity! and!reactivity.! Click! chemistry! did! not! gain! momentum! until! his! group's! discovery! of! CuAAC!(the!copper]catalyzed!azide]alkynecycloaddition),! a!near]perfect!reaction! (2002).! Recently!the!Sharpless!group!discovered!SuFEx,!also!near]perfect!for!click!chemistry.!In!concert!with!the!thiol]ene!reaction,!these!three!make!click!chemistry!a!far]reaching!method!for!discovery!chemistry.!

In!2011!Thomson!Reuters!named!the!top!100!chemists!whose!papers!published!in!the!first!decade!of!the!21st!Century!achieved!the!highest!citation!impact!scores:!Sharpless!was!#4.!

Sharplesses'! mentors! at! Dartmouth! (BA! ,1963),! Stanford! (PhD,! 1968,! and! postdoc),! and!Harvard! (postdoc)!were!Professors!T.!A.! Spencer,! E.! E.! van!Tamelen,! J.! P.!Collman,!and!K.!Bloch,! respectively.! Before! joining! The! Scripps! Research! Institute! (TSRI)! in! 1990! as!W.!M.!Keck! Professor! of! Chemistry,! he! was! a!long]time!member! of! the! MIT! chemistry! faculty,!except!for!three!years!at!Stanford!(1977]1980)!

Some!of!Sharplesses'!honors!include!the!Chemical!Sciences!Award!of!the!National!Academy!of! Sciences! (elected!member,! 1985),! the!Roger!Adams!and!Arthur!C.! Cope!Awards!of! the!American!Chemical!Society,!the!Tetrahedron!Award,!the!King!Faisal!Prize,!the!Prelog!Medal,!the!Wolf!Prize,!and!over!twenty!honorary!doctorates!and!professorships.! !

!!

73!

Exploring*The*Sulfate*World*

*

Making!stable!molecular!links!is!click!chemistry's!core.!Now!there!are!three!linker!methods!that! are! near]perfect! for! click! chemistry:! 1)! SuFEx,! the! new! catalytic! sulfuryl! fluoride!exchange,! and! 2)! CuAAC,! copper]catalyzed! azide]alkyne! cycloaddition,! both! from! our!laboratories;!and!3)!the!radical]mediated!thiol]ene!reaction!developed!in!the!laboratory!of!the!late!Charles!Hoyle,!who!for!decades!championed!the!versatility!of!thiol]ene!couplings.!

Finding!SuFEx!was!as! impossible!to!predict! (a!characteristic!of!the!genuinely!new)!as!Peak!Performance's!meeting!up!with!Arthur!in!Ecuador!!!

Our!Ecuadorian!jungle!was!the!search!for!a!more!robust!sulfur]connecting!protocol.!Instead!of! starting!with!a!meatball,! SuFEx! started!with! sulfuryl! fluoride.!And!because!both!Arthur!and! SO2F2! are! genuine! singularities—small! (dog! and! molecule)! but! apparently!unbreakable—the!former!now!lives!in!Sweden!and!the!later!became!the!parent!to!SuFEx.!!!

SO2F2! is! so! phenomenally! stable! that! it!was! considered!de# facto! inert.! Add! its! deadliness!(SO2F2!became!a!widely]used!fumigant!gas!that!kills!all!life),!and!the!result!was!the!sulfuryl!fluorides!no!longer!being!investigated!by!chemists.!!

Why!our!group!did!pursue!SO2F2,!how!we!made! it! reactive,!where! its!enormous!reactivity!constraints! led!us,! and! its! remarkable!acid]base! kinship!with! the! chemistry!of! life,!will! be!discussed.! Why! exploiting! click! chemistry! requires! "perfect"! reactions! will! be! explained.!Examples!will!show!how!SuFEx!reactions!are!the!portal!to!previously!unknown,!so!hitherto!wholly! unexplored,! galaxies! within! the! chemical! universe.! Possible! explanations! for! the!mysteries!of!SuFEx! transformations,!a! few!of!my! favorite!SuFEx! surprises,!and!predictions!(i.e.!informed!wild!guesses)!will!follow.! !

!!

74!

Professor*Sir*John*Meurig*Thomas*University!of!Cambridge,!United!Kingdom!!John!Meurig! Thomas! taught! and! researched! at! the!University! of! Wales! (Bangor! and! Aberystwyth)!before! moving! to! the! University! of! Cambridge! as!Head! of! the! Department! of! Physical! Chemistry! in!1978.! ! He! was! appointed! Director! of! the! Royal!Institution!of!Great!Britain,!London!in!1986!and!also!the!Director!of!the!Davy!Faraday!Laboratory.!!In!1993!he!became!Master!(Head)!of!Peterhouse,!the!oldest!college! in! the! University! of! Cambridge.! ! Since! that!time!he!has!been!Honorary!Professor!of! Solid]State!Chemistry! in! the! Department! of! Materials! Science,!Cambridge.!

His! early! work! was! concerned! with! the!characterization! and! chemical! consequences! of!dislocations! and! other! structural! defects! in!molecular! crystals,! certain! minerals! and! layered!solids.! !He!was!one!of!the!first! to!exploit!and!adapt!electron! microscopy! as! an! indispensable! chemical!tool.!!From!the!mid]1990s,!with!his!combined,!simultaneous!use!of!X]ray!absorption!and!X]ray!diffraction,!coupled!with!GC/MS/FTIR,!he!achieved!new!in#situ!insights!into!the!mode!of!operation!of!his!molecularly!designed!heterogeneous!catalysts!for!the!production!of!a!wide!range! of! new!materials.! ! His! approach! to! active! site! engineering,! which! earned! him! the!Willard]Gibbs! gold!medal! and! the! first!Amer.# Chem.# Soc#Award! for! “Creative# Research# in#Homogeneous#and#Heterogeneous#Catalysis”# (in!1999),!has! led!to! the!design!of!numerous!nanoporous! single]site! catalysts,! where! the! advantages! of! both! homogeneous! and!heterogeneous!catalysts!are!unified.!

Early! work! of! his! in! geochemistry! was! recognized! when! a! new! mineral,!meurigite,! was!named!in!his!honour.!!He!is!a!keen!populariser!of!scientific!culture,!for!which,!along!with!his!services!to!chemistry,!he!was!knighted!in!1991.!! !

!!

75!

Tomorrow’s*Catalysts:*Actual*And*Desired*

!

Catalysts! are! the! backbone! of! the! chemical! industry.! ! They! are! of! central! importance! in!generating!the!materials!that!sustain!and!improve!the!quality!of!civilized!life.!!They!are!also!of!pivotal!importance!in!the!production!and!storage!of!energy,!as!well!as!of!petrochemicals!and!all!the!materials!derived!from!them.!

For!environmental,!economic!and!political! reasons!there! is!a!pressing!need!to!rely! less!on!non]renewables!and!more!on!renewable!feedstocks!and!also!to!devise!processes!that,!with!the! aid! of! judiciously! designed! new! catalysts,! produce! no! waste! or! cause! pollution.! ! In!addition,! for! many! of! the! bulk! materials,! fine! chemicals! and! pharmaceuticals! now! in!extensive! use,! ecologically! responsible! and! otherwise! desirable! improvements! in!preparation! and!performance!need! to!be!made! to! existing! catalysts! by!harnessing! recent!advances!in!nanoscience!and!nanotechnology.!

The! search! for! atom]efficient! heterogeneous! catalysts,! especially! as! applied! to! the!expensive! platinum! group! metals! and! other! widely! used! catalysts,! has! recently!intensified;[1,2]! and! considerable! progress! of! a! fundamental! kind! has! been! made! in! the!design!and!operation!of!efficient!new!single]site,!as!well!as!single]atom,!catalysts.!!Materials!chemical! techniques! can! be! used! to! fashion! new,! nanoporous! (single]site)! catalysts!composed!of!earth]abundant!elements!such!as!Al,!Si,!O;!and!also!to!construct!single]atom!catalysts! composed! of! expensive! and! relatively! rare! metals! such! as! Pt,! Pd,! Ir! and! Au!supported!on!high]area!benign!and!plentiful!oxides.!!Advances!in!a!selection!of!both!in#situ!and!ex#situ!techniques!have!greatly!facilitated!the!design!and!characterization!of!these!novel!catalysts.!

*

• M.! Yang! and! M.! Flytzani]Stephanopoulos! et# al.# # A! common! single]site! Pt(II).O.(OH)x!species! stabilized! by! sodium! on! ‘active’! and! ‘inert’! supports! catalyzes! the! water]gas!shift!reaction!(CO+H2O→CO2+H2).!!J.#Amer.#Chem.#Soc.,#(2015),!DOI!10.1021/ja513292k.!

• J.!M.!Thomas!and!W.!J.!Thomas,!“Principles#and#Practice#of#Heterogeneous#Catalysts”,!2nd!Edition,!Wiley]VCH,!(2015).! !

!!

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Professor*Peter*von*Hippel*University!of!Oregon,!United!States!!Peter!von!Hippel!received!his!undergraduate!and!graduate!education!at!MIT,!culminating!in!a!Ph.D.!degree! in!Quantitative!Biology!and!Biophysics! in!1955.! His! thesis! research! involved! working! out!how!the!various!protein! (casein)! components!of!skim! milk! interacted! in! forming! stable! casein!micelles,!which! turned!out! to! be! stabilized!by! a!balanced! set! of! hydrophobic! and! electrostatic!interactions.!As!a!postdoctoral!fellow!von!Hippel!worked! at! the!Naval!Medical! Research! Institute!(Bethesda,! MD)! on! solution! studies! of! muscle!contraction! mechanisms,! including! studies! of!ATP]driven! conformational! changes! in!actomyosin.! He! then! moved! to! Dartmouth!Medical! School! (Hanover,! NH)! as! an! Assistant!and! Associate! Professor! of! Biochemistry,! and!their! lab! carried! out! research! on! the! effects! of!solvent! modifiers,! including! the! Hofmeister!series!of!ions,!on!the!structure!and!stability!of!globular!and!fibrous!proteins.!They!also!used!hydrogen!exchange!methods! to!make! the! first!measurements!of! the! ‘breathing’! reactions!(base]pair!opening!and!closing)!of!duplex!DNA.!!!In!1967!their!research!group!moved!to!the!Institute!of!Molecular!Biology!at!the!University!of!Oregon,! where! they! started! to! work! on! the! molecular! mechanisms! of! protein]DNA!interactions,!using!the!control!of!transcription!by!E.#coli#lac!repressor!and!RNA!polymerase!as!our!model! systems.!Soon! they!added!studies!of! the!proteins!and!protein!complexes!of!the!DNA!replication!system!of!E.#coli#bacteriophage!T4!as!well.!The!assembly!and!function!of!these! systems!as!paradigmic!models! for!understanding! the! ‘macromolecular!machines’!of!DNA! transcription! and! replication! has! largely! occupied! their! lab! ever! since.! Von! Hippel!research!group!has!put!out!about!250!research!papers!in!these!general!research!areas,!and!this!work!has!been!supported!by!multiple!grants! from!NIH,!NSF!and!the!American!Cancer!Society,! and! also! resulted! in! election! to! the!National! Academy!of! Sciences,! the!American!Academy!of!Arts!and!Sciences,!and!the!American!Philosophical!Society.!!!Along!the!way!von!Hippel!has!served!as!Chair!of!the!Biochemistry!Department!at!Dartmouth!Medical! School,! and! then!Director!of! the! Institute!of!Molecular!Biology!and! subsequently!also! Chair! of! Chemistry! at! the!University! of!Oregon.!He! has! held!many! advisory! roles! for!federal! agencies,! and!been!much! involved!with!professional! societies! and! journal! editing.!Since! 1999! von! Hippel! has! been! a! Research! Professor! at! the! University! of! Oregon,! and!continue! to!maintain! an! active! research! laboratory!working! on! various! aspects! of! nucleic!acid]protein!interactions!by!single!molecule!and!bulk!solution!techniques.! !

!!

77!

The* Multiple* Roles* Of* The* NonN(Sequence)NSpecific* Binding* Of* GenomeNRegulatory*Proteins*To*DNA*In#Vitro*And*In#Vivo”!!The!base]pair! sequences!of! the!DNA!genome! carry! the! central! structural,! developmental,!functional,! regulatory! and! transcriptional! coding! information! needed! to! direct! cellular!processes,!but!this!information!must!be!read!and!exploited!by!proteins.!Much!attention!has!been! paid! to! how! functional! and! regulatory! proteins! recognize! and! interact!with! specific!double]stranded!(ds])!DNA!target!sites,!but!much! less!thought!has!been!given!to!why!and!how!proteins!bind!to!DNA!in!the!first!place,!and!how!general!non]sequence]specific!features!of!DNA!underlie!and!control!essentially!all!aspects!of!DNA]regulated!cellular!function.!In!this!overview!I!will!attempt!to!summarize!what!is!known!about!these!issues,!based!on!old!and!new!work!from!our!lab!and!others!and!focusing!–!as!examples!–!on!nonspecific!DNA!binding!studies!of!E.#coli!lac!repressor!and!RNA!polymerase!and!the!single]stranded!binding!protein!(gp32)!of!the!bacteriophage!T4!DNA!replication!system.!!!I!will! start!with! the! basic! thermodynamic! forces! and! interactions! that! drive! the! assembly!and!stabilization!DNA]protein!complexes,!and!then!describe!how!sequence]specific!protein]DNA! binding! affinities! depend! on! thermodynamic! coupling! to! nonspecific! DNA! binding!interactions.! I! will! also! consider! how! the! polyelectrolyte! nature! of! DNA! leads! to! ion!condensation!and!thus!makes!possible!facilitated!diffusion!of!proteins!in!the!nonspecifically!bound!state,!how!this!facilitated!diffusion!can!perturb!the!dynamics!of!specific!DNA!target!site! location! and! docking,! and! how! other! DNA]bound! proteins! and! protein! complexes!interfere! with! and! direct! these! processes! in# vitro! and! in# vivo.! Finally! I! will! discuss! how!proteins,!whose!primary!(or!even!sole)!activity!is!nonspecific!binding!to!single]!and!double]stranded! DNA,! interact! with! and! manipulate! such! DNA! sequences! in! discharging! their!biological!functions.!! !

!

!

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Professor*Ariel*Warshel*University!of!Southern!California,!United!States!

!

Arieh! Warshel,! Distinguished! Professor! of!

Chemistry! at! the! University! of! Southern!

California’s!Dornsife!College!of! Letters,!Arts! and!

Sciences,!was!awarded!a!Nobel!Prize!in!2013!for!

his! groundbreaking! research! in! theoretical!

chemistry.!Dr.!Warshel!holds!the!Dana!and!David!

Dornsife!Chair!in!Chemistry!at!USC,!where!he!has!

served!on!the!faculty!since!1976.!!

!

A!member!of!the!National!Academy!of!Sciences,!

Dr.!Warshel!has!pioneered!computer!simulations!

of! the! functions! of! biological!molecules.! He! has!

authored! nearly! 400! peer]reviewed! articles,!

including! the! book,! Computer# Modeling# of#Chemical# Reactions# in# Enzymes# and# Solutions#(Wiley! Professional,! 1991.)! He! co]developed!

computer! programs! for! molecular! simulations!

which! have! been! used! extensively! in! different!

applications!including!the!development!of!new!pharmaceuticals.!He!and!his!coworkers!have!

pioneered! key! approaches! for! simulating! the! functions! of! biological! molecules,! including!

introducing!molecular!dynamics!in!biology,!developing!the!quantum!mechanical/molecular]

mechanical!(QM/MM)!approach,!introducing!simulations!of!enzymatic!reactions,!pioneering!

microscopic!simulations!of!electron!transfer!and!proton!transfer!in!solutions!and!in!proteins,!

pioneering!microscopic!modeling!of!electrostatic!effects!in!macromolecules!and!introducing!

simulations! of! protein! folding! .! He! and! his! coworkers! have! also! elucidated! recently! the!

molecular!origin!of!the!vectorial!action!of!molecular!machines.!

!!

Dr.!Warshel!holds!a!B.Sc.!Summa!Cum!Laude!in!chemistry!from!Technion–Israel!Institute!of!

Technology! in!Haifa,! Israel,! and!both!an!M.Sc.! and!Ph.D.! in! chemical!physics! from! Israel’s!

Weizmann! Institute! of! Science.! Prior! to! joining! USC,! he! was! a! postdoctoral! scholar! at!

Harvard!University!and!a!senior!scientist!and!associate!professor!at!the!Weizmann!Institute.!

In!paralel!he!was!also!an!European!Molecular!Biology!Organization!fellow!at!the!Laboratory!

of!Molecular!Biology!at!Cambridge!University.!

!

An! honorary! member! of! the! Royal! Society! of! Chemistry! (RSC),! Dr.! Warshel’s! numerous!

awards! include!the!American!Chemical!Society’s!Tolman!Medal,!the!RSC’s!Soft!Matter!and!

Biophysical!Chemistry!Award!in!2012,!and!the!Biophysical!Society’s!Founders!Award.!!

!

Dr.!Warshel!was! raised!on!Kibbutz!Sde]Nahum! in!northern! Israel!and!served! in! the! Israeli!

Army! from! 1958! to! 1962! (Reserved! Rank! Captain).! Dr.!Warshel’s! family! includes! his!wife!

Tamar;!daughters,!Merav!and!Yael;!and!three!grandchildren,!Maya,!Danielle!and!Neev.! !

!

!

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Evaluating*And*Using*Free*Energy*Landscapes*For*Biological*Functions*!

Despite!the!enormous!advances!in!structural!studies!of!biological!systems!we!are!frequently!

left!without!a! clear! structure! function! correlation!and!cannot! fully!describe!how!different!

systems! actually! work.! This! introduces! a! major! challenge! for! computer! modeling!

approaches!that!are!aimed!at!a!realistic!simulation!of!biological! functions.!The!unresolved!

questions!range!from!the!elucidation!of!the!basis!for!enzyme!action!to!the!understanding!of!

the!directional!motion!of!complex!molecular!motors.!Here!we!focus!on!describing!the!use!

our!electrostatic!augmented!coarse!grained!(CG)!model!(1)!and!the!renormalization!method!

to! simulate! the! action! of! different! challenging! complex! systems.! It! is! shown! that! our! CG!

model! produces,! for! the! first! time,! realistic! landscapes! for! vectrorial! process! such! as! the!

actions!of!F1!ATPase!(2),!F0!ATPase!(3)!and!myosin!V!(4).!It!is!also!shown!that!such!machines!

are!working!by!exploiting! free!energy!gradients!and!cannot! just!use!Brownian!motions!as!

the! vectroial! driving! force.! Significantly,! at! present,! to! the! best! of! our! knowledge,! theses!

studies!are!the!only!studies!that!reproduced!consistently!(rather!than!assumed)!a!structure!

based!vectorial!action!of!molecular!motors.!Special!emphasis!is!placed!on!the!challenge!of!

evaluating! the! torque! of! molecular! motors! and! on! the! need! of! generating! the! relevant!

landscapes.!!

!

!

1 Coarse]Grained! (Multiscale)! Simulations! in! Studies! of! Biophysical! and! Chemical!

Systems,!S.!C.!!!L.Kamerlin,!S.!Vicatos,!A.!Dryga!and!A.!Warshel,!,!Ann.!Rev.!Phys.!Chem.!

62,41!(2011).!

2 Electrostatic! Origin! of! The! Mechanochemical! Rotary! Mechanism! And! The! Catalytic!

Dwell!of!F1]ATPase,!S.!Mukherjee!and!A.Warshel,!Proc.!Natl.!Acad.!Sci.!USA!,108,!!20550!

(2011).!

3 Realistic!simulations!of!the!coupling!between!the!protomotive!force!and!the!mechanical!

rotation!of!the!F0]ATPase,!Proc.!Natl.!Acad.!Sci.!USA,!109,14876!(2012).!!

4 !Electrostatic!origin!of! the!unidirectionality!of!walking!myosin!V!motors,!S.!Mukherjee!

and!!A.!Warshel!,!Proc.!Natl.!Acad.!Sci.!USA,!,110!,!17326]17331!(!2013).!!

5 Dissecting! the! role! of! the! γ]subunit! in! the! rotary–! chemical! coupling! and! torque!

generation!of!F1]ATPase,!S.!Mukherjee!and!A.!Warshel,!Proc.Natl.!Acad.!Sci.!USA!112:!

2746]2751!(2015).! !

!!

80!

Professor*George*Whitesides*Harvard!University,!United!States!

!

George! M.! Whitesides! was! born! August! 3,! 1939! in!Louisville,! KY.! ! He! received! an! A.B.! degree! from!Harvard! University! in! 1960! and! a! Ph.D.! from! the!California!Institute!of!Technology!(with!J.D.!Roberts)!in!1964.! ! He! was! a! member! of! the! faculty! of! the!Massachusetts! Institute! of! Technology! from! 1963! to!1982.! ! He! joined! the! Department! of! Chemistry! of!Harvard! University! in! 1982,! and! was! Department!Chairman! 1986]89,! and! Mallinckrodt! Professor! of!Chemistry!from!1982]2004.!He!is!now!the!Woodford!L.!and!Ann!A.!Flowers!University!Professor.!

Among!his!memberships!and!fellowship!are:!Member,!American! Academy! of! Arts! and! Sciences,! National!Academy! of! Sciences,! National! Academy! of!Engineering,!American!Philosophical!Society;!Fellow!of!the! American! Association! for! the! Advancement! of!Science,! Institute! of! Physics,! American! Physical!Society,! New! York! Academy! of! Sciences,! World!Technology!Network,!and!American!Chemical!Society;!Foreign!Fellow!of!the!Indian!National!Academy! of! Science;! Honorary! Member! of! the! Materials! Research! Society! of! India;!Honorary!Fellow!of!the!Chemical!Research!Society!of!India,!Royal!Netherlands!Academy!of!Arts! and! Sciences,! Royal! Society! of! Chemistry! (UK);! Foreign! Associate! of! the! French!Academy!of! Sciences;!Honorary! Professor,! Academy!of! Scientific! and! Innovative! Research!(AcSIR),!India.!

Whitesides! resent! research! activities! include! physical! and! organic! chemistry,! materials!science,! biophysics,! water! in! biology,! surface! science,! microfluidics,! self]assembly,! micro]!and! nanotechnology,! science! for! developing! economies,! the! origin! of! life,! rational! drug!design,!magnetic!levitation,!dissipative!systems!and!emergence,!complexity,!and!simplicity.!! !

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81!

Origin*Of*Life,*And*CellNSurface*Biochemistry*

!

Not#available#

! !

!!

82!

Professor*Kurt*Wüthrich*The!Scripps!Research!Institute,!United!States!!!Kurt! Wüthrich! is! the! Cecil! H.! and! Ida! M.! Green!Professor! of! Structural! Biology! at! The! Scripps!Research!Institute,!La!Jolla,!CA,!USA,!and!a!Professor!of!Biophysics!at! the!ETH!Zürich,!Zürich,!Switzerland.!His! research! interests! are! in! structural! biology! and!structural! genomics.! ! His! specialty! is! nuclear!magnetic! resonance! (NMR)! spectroscopy! with!biological! macromolecules,! where! he! contributed!the! NMR! method! of! three]dimensional! structure!determination! of! proteins! and! nucleic! acids! in!solution.! ! Kurt!Wüthrich’s! achievements! have! been!recognized! by! the! Prix! Louis! Jeantet! de! Médecine,!the!Kyoto!Prize! in!Advanced!Technology,! the!Nobel!Prize!in!Chemistry,!and!by!a!number!of!other!awards!and!honorary!degrees.! !

!!

83!

*Sunset*of*the*NIH*Protein*Structure*Initiative*–*What*Next?*!A!survey!will!be!provided!of!the!fifteen]year!history!of!the!Protein!Structure!Initiative!(PSI)!from!2000–2015.!The!main!focus!will!be!on!the!stated!goals!for!the!three!five]year!project!periods!of!the!PSI.!Illustrations!will!be!taken!from!the!area!of!my!research!team,!i.e.,!the!use!of! solution! NMR! spectroscopy! in! PSI! projects.! An! attempt! will! be! made! to! evaluate! the!impact!of!the!achievements!of!the!PSI!for!future!biological!and!biomedical!research.!!! *

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84!

Professor*Toshio*Yanagida*Osaka!University,!Japan!!Toshio!Yanagida!received!the!B.!Eng.!Sci.!degree!in!1969,!the!M.!Eng.!Sci.!degree!in!1971,!and!the!D.E.!degree! in! 1976,! all! from!Osaka!University,! Osaka,!Japan.! He! is! currently! Director! of! both! the! RIKEN!Quantitative! Biology! Center! (QBiC)! and! of! the!Center! for! Information! and! Neural! Networks!(CiNet),!NICT,!while!also!holding!the!titles!of!Vice]director!at!the!WPI!Immunology!Frontier!Research!Center,!Osaka!University,! and! Specially!Appointed!Professor! at! the! Graduate! School! of! Frontier!Biosciences!(FBS),!Osaka!University.!!Previously,! he! was! a! Professor! at! Osaka!University’s! Department! of! Physiology! and!Biosignaling,! Graduate! School! of! Medicine! from!1996]2010,! and! at! the! FBS! 2002]2010.! He! was!Project!Leader!of!the!Yanagida!Biomotron!Project,!ERATO,! JST! from!1993]1997!and! its!successor,! the!Single!Molecule! Process! Project,! ERATO,! JST! from!1998]2002.!Dr.!Yanagida!was!also!Research!Director!of!Soft!Nano!Machines!and!Research!Supervisor!of!Novel!Measuring!and!Analytical!Technology!Contributions! to! the!Elucidation!and!Application!of!Life!Phenomena,!CREST,!JST!from!2004]2012.!All!of!these!projects!revolve!around!his!research!interest!on!the!role!of!signal!fluctuation!in!the!function!of!bio]systems!ranging!from!the!molecular!machine!to!the!human!brain.!!!Finally,!Dr.!Yanagida!has!received!a!number!of!prestigious!awards!including!the!25th!Naito!Memorial! Science!Promotion!Award! (Naito!Memorial!Promotion!Foundation)! in!1994,! the!Japan! Academy! Award! and! the! Imperial! Award! in! 1998,! and! an! Asahi! Award! (Asahi!Newspaper!Culture!Foundation)! in!1999.!In!2010,!he!was!awarded!the!US!Genomic!Award!for!Outstanding! Investigator! in! the! Field! of! Single!Molecule! Fluorescence!Microscopy! and!made! a! Fellow! of! the! US! Biophysical! Society! in! 2011,! and! a! Person! of! Cultural! merit!(Ministry!of!Education,!Culture,!Sports,!Science!and!Technology!in!Japan:!MEXT)!in!2013.! !

!!

85!

Role*Of*Fluctuations*For*Driving*BioNMolecular*Machine*!Since!biological!molecular!machines!such!as!molecular!motors,!cell!signal!processors,!DNA!transcription!processors! and!protein! synthesizers! are! only! nanometers! in! size! and!have! a!flexible!structure,!they!are!very!prone!to!thermal!agitation.!Furthermore,!the!input!energy!level! is!not!much!different!from!that!of!average!thermal!energy,!kBT.!Molecular!machines!do!not!avoid!this!thermal!noise,!but!rather!use!it!for!their!functions.!This!is!in!sharp!contrast!to!man]made!machines!that!operate!at!energies!much!higher!than!thermal!noise.!In!recent!years,! single! molecule! imaging! and! nano]technologies! have! rapidly! been! expanding! to!include! a!wide! range!of! life! science! applications.! The!dynamic!properties! of! biomolecules!and! the! unique! operations! of! molecular! machines,! which! were! previously! hidden! in!averaged!ensemble!measurements,!are!now!being!unveiled.!!The!aim!of!our!research!is!to!approach!the!engineering!principle!of!adaptive!biological!systems!by!uncovering!the!unique!operation!of!biological!molecular!machines.!!!Here,! I! review!our!single!molecule!experiments!designed!to! investigate!molecular!motors,!enzyme!reactions,!protein!dynamics!and!cell!signaling,!and!discuss!how!thermal!fluctuations!(noise)! play! a! positive! role! in! the! unique! operation! of! biological! molecular! machines!allowing!for!flexible!and!adaptive!biological!systems!including!cell!and!brain.! !

!!

86!

Professor*Ada*Yonath*Weizmann!Institute!of!Science,!Israel!!Ada! Yonath! graduated! the! Hebrew! University!(in! chemistry),! earned! Ph.D.! from! Weizmann!Institute!(WIS)!and!completed!her!postdoctoral!education!at!Mellon!Institute!and!MIT,!USA.!In!the! seventies! she! established! the! first!laboratory! for! structural! biology! in! Israel,! the!only! laboratory! of! this! kind! in! the! country! for!almost! a! decade.! At! WIS! she! is! WIS! Kimmel!Professor! and! the! Director! of! Kimmelman!Center! for! Biomolecular! Structure.! In! parallel,!during!1980]1986!she!was!a!visiting!scientist!at!Max! Planck! for! Molecular! Genetics! in! Berlin!and!during!1986]2004!she!headed!Max]Planck]Research]Unit! for! Ribosome! Structure! in!Hamburg.!!!She! is! a!member!of! the!US!National!Academy!of! Sciences! (NAS);! the! American! Academy! of!Arts! and! Sciences;! the! Israel! Academy! of! Sciences! and! Humanities;! the! German! Science!Academy!(Leopoldina);!the!European!Academy!of!Sciences!and!Art;!the!Korean!Academy!for!Science! and! Technology;! the! European! Molecular! Biology! Organization! (EMBO);! the!Microbiology!Academy;!the!International!Academy!of!Astronautics;!the!UK!Royal!Society!for!Chemistry!and!the!Pontificia!Accademia!delle!Scienze!(Vatican).!!!She!holds!honorary!doctorates!from!Oslo,!NYU,!Mount!Sinai,!Oxford,!Cambridge,!Hamburg,!Berlin]Technical,!Patras,!Greece;!De!La!Salle!University,!Manila,!and!most!Israeli!Universities.!Her!awards!include!the!Israel!Prize;!Paul]Karrer!Medal;!Louisa]Gross]Horwitz!Prize;!Ehrlich]Ludwig! Medal;! Linus! Pauling! Gold! Medal;! Anfinsen! Prize;! Wolf! Prize;! UNESCO/L’Oreal!Award;!Albert]Einstein!World!Award! for!Excellence;!DESY!pin;!KEK!distinction;!Erice!Peace!Prize;!Florence!Cite!Medal;!Maria!Sklodowska]Curie!Medal;!Nobel!Prize!for!Chemistry.!!! !

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87!

SpeciesNSpecific*Antibiotics*And*The*Microbiome*!!The!current!global!escalation!in!resistance!to!antibiotics!is!a!serious!threat,!as!it!seems!that!the!world!is!headed!for!a!post]antibiotic!era,!in!which!common!infections!and!minor!injuries!that! have! been! treatable! for! last! decades! could! become! fatal! again.! Ribosomes,! the!universal! cellular!machines! that! translate! the!genetic!code! into!proteins,!are!paralyzed!by!many! clinically! useful! antibiotics.! The! structures! of! ribosomes! from! non]pathogenic!bacteria,!used!as!models!for!genuine!pathogens,!illuminated!the!antibiotics!binding!modes,!inhibitory!actions,!synergism!pathways,!the!differentiation!between!patients!vs.!pathogens!and!mechanisms!leading!to!bacterial!resistance.!!!However,!as!species!specific!diversity!was!detected! in!susceptibility! to! infectious!diseases,!our!structural!studies!have!been!extended!to!ribosomes!from!genuine!pathogens.!The!high!resolution!structures!of! the! ribosomal!particle! from!a!genuine!multi]resistant!pathogen! in!complex! with! several! antibiotics,! highlighted! subtle,! albeit! highly! significant! structural!elements!that!can!account!partially!or!fully!for!species!specificity!and!may!lead!to!the!design!of!species!specific!drug,!while!preserving!the!microbiome.!! !

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88!

Professor*Richard*Zare*Stanford!University,!United!States!!Born!on!19!November,!1939!in!Cleveland,!Ohio,!USA,!Dr.! Richard! Zare! is! the! Marguerite! Blake! Wilbur!Professor! in! Natural! Science,! Department! of!Chemistry,! Stanford! University.! His! research! covers!many!different!areas!but!is!quite!noted!for!advances!in! laser! chemistry,! resulting! in! a! greater!understanding! of! chemical! reactions! at! the!molecular!level!and!contributing!very!significantly!to!solving!a!variety!of!problems!in!chemical!analysis.!His!development! of! laser! induced! fluorescence! as! a!method! for! studying! reaction! dynamics! has! been!widely!adopted!in!other!laboratories.!Awards!include!the!U.S.!National!Medal!of!Science!(1983),!the!Welch!Award! in! Chemistry! (1999),! the! Wolf! Prize! in!Chemistry!(2005),!the!BBVA!Foundation!Frontiers!of!Knowledge!Award! in! the!Basic! Sciences! (2010),! and!the!King!Faisal! International!Prize! in!Science! (2011).!He! has! also! received! honorary! doctorates! from!Uppsala! University! and! Chalmers! Institute! of!Technology!among!other!institutions.!!!!His!memberships!include!the!National!Academy!of!Sciences,!the!Royal!Society,!the!Swedish!Royal! Academy! of! Engineering! Sciences,! the! Chinese! Academy! of! Sciences,! the! Indian!Academy!of!Sciences,!and!The!World!Academy!of!Sciences!(TWAS)!for!developing!countries.!From!1992!to!1998,!he!served!on!the!National!Science!Board,!the!policy!making!board!of!the!United! States! National! Science! Foundation,! the! last! two! years! as! its! Chair.! ! He! presently!chairs!COSEPUP,! the!Committee!on!Science,!Engineering!and!Public!Policy!of! the!National!Academy!of!Sciences,!the!National!Academy!of!Engineering,!and!the!Institute!of!Medicine.!! !

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89!

Acceleration*of*Reactions*in*Charged*Microdroplets*!Using!high]resolution!mass!spectrometry,!we!have!studied!the!synthesis!of!isoquinoline!in!a!charged!electrospray!droplet!and!the!complexation!between!cytochrome!c!and!maltose!in!a!fused!droplet!to!investigate!the!feasibility!of!droplets!to!drive!reactions!(both!covalent!and!noncovalent!interactions)!at!a!faster!rate!than!that!observed!in!conventional!bulk!solution.!In!both!cases!we!found!marked!acceleration!of!reaction,!by!a!factor!of!a!million!or!more!in!the! former!and!a! factor!of!a! thousand!or!more! in! the! latter.!We!believe!that!carrying!out!reactions!in!microdroplets!(about!1!–!15!μm!in!diameter!corresponding!to!0.5!pL!]!2!nL)!is!a!general!method! for! increasing! reaction! rates.!The!mechanism! is!not!presently!established!but!droplet!evaporation!and!droplet!confinement!of!reagents!appear!to!be!two!important!factors!among!others.!In!the!case!of!fused!water!droplets,!evaporation!has!been!shown!to!be! almost! negligible! during! the! flight! time! from! where! droplet! fusion! occurs! and! the!droplets! enter! the! heated! capillary! inlet! of! the!mass! spectrometer.! This! suggests! that! (1)!evaporation!is!not!responsible!for!the!acceleration!process!in!aqueous!droplet!fusion!and!(2)!the!droplet]air! interface!may!play!a!significant!role! in!accelerating!the!reaction.!We!argue!that!this!'microdroplet!chemistry'!could!be!a!remarkable!alternative!to!accelerate!slow!and!difficult!reactions,!and!in!conjunction!with!mass!spectrometry,!it!may!provide!a!new!arena!for!studying!chemical!and!biochemical!reactions!in!a!confined!environment.! !

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90!

Professor*Ahmed*Zewail*California!Institute!of!Technology,!United!States!

Ahmed! Zewail! is! the! Linus! Pauling! Chair! professor! of!chemistry! and!physics,! and!director!of! the!Center! for!Physical!Biology!at!Caltech.!He! is! the!sole!recipient!of!the!1999!Nobel!Prize!for!the!development!of!the!field!of!Femtochemistry.! In! the!post]Nobel!era,! he!developed!4D# Electron# Microscopy#for! the! direct!visualization!of!matter! in!space!and!time.!Dr.!Zewail’s!other!honors!include!fifty!Honorary!Degrees,!Orders!of!Merits,! Postage! Stamps! and! more! than! hundred!international! awards.! He! has! published! some! 600!articles! and! 14! books! and! is! known! for! his! effective!public! lectures! and! writings,! not! only! on! science! but!also! in! global! affairs.! For! his! leadership! role! in! these!world! affairs,! he! received,! among! others,! the! “Top!American! Leaders!Award”! from!The!Washington!Post!and!Harvard!University.!!

In!2009,!President!Barack!Obama!appointed!him!to!the!Council!of!Advisors!on!Science!and!Technology,!and!in!the!same!year!he!was!named!the!first!U.S.!Science!Envoy!to!the!Middle!East.!Subsequently,!the!Secretary!General!of!the!United!Nations!Ban!Ki]moon!invited!Dr.!Zewail!to!join!the!UN!Scientific!Advisory!Board.!In!2014,!President!El!Sisi!decreed!his!appointment!to!the!Council!of!Advisors!for!the!State!of!Egypt.!Following!the!2011!Egyptian!revolution,!the!government!established! “Zewail! City! of! Science! and! Technology”! as! the! national! project! for! scientific!renaissance,!and!Dr.!Zewail!became!its!first!Chairman!of!the!Board!of!Trustees.!

! !

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Seeing*with*Electrons*in*Four*Dimensions*

!

Seeing! in! the!microscopic!world! is! usually! done! through!photons! or! electrons.! !However,!when!the!constituent!matter! requires!an!atomic]scale! resolution,!electrons!accelerated!to!high!speeds!become!the!method!of!our!choice.! ! In!this!talk,!we!will!highlight!the!concepts!behind! a! new! approach! for! electron! imaging—it! enables! visualization! in! the! three!dimensions!of!space!and!an!increase!in!the!time!resolution!by!10!orders!of!magnitude.!This!development!of!“4D!Electron!Microscopy”!has!proven!significant!in!many!applications,!and!we!shall!present!some!including!the!behavior!of!nano]musical!systems!and!that!of!biological!structures.!!The!collected!works!over!the!past!15!years!can!be!found!in!reference!(3).!

!

• Filming!the!Invisible!in!4D.!A.!H.!Zewail,!Sci.!Am.!303,!74!(2010).!• Four]Dimensional!Electron!Microscopy.!A.!H.!Zewail,!Science!328,!187]193!(2010).!• 4D!Visualization!of!Matter:!Recent!Collected!Works.!H.!Zewail,! Imperial!College!Press,!

London!(2014).! !

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Chairs*and*Moderators*

Professor*Bo*Albinsson*Chalmers!University!of!Technology,!Sweden!!Bo! Albinsson! has! MSc! and! PhD! (1993)! from!Chalmers! University! of! Technology! and! was!post]doctoral! fellow! at! the! University! of!Colorado! before! returning! to! Sweden! as! an!assistant! professor! funded! by! the! Swedish!research! council! in! 1995.! In! 2003! he! became!full!professor!of!Physical!Chemistry!at!Chalmers!and!has!since!then!been!leading!a!medium!size!research! group.! In! the! Albinsson! research!group! we! are! interested! in! photo]induced!processes! ranging! from!mechanistic! studies! of!energy! and! electron! transfer! reactions! with!relevance! for! solar! energy! research! to! novel!functionalized! nanostructures! based! on! DNA!nanotechnology.!We!use!advanced!laser]based!time]resolved! spectroscopic! techniques!combined! with! traditional! spectroscopy! and!theoretical! (quantum!mechanical)!methods.! In!order! to!get! access! to! complex!molecular! and/or!bimolecular! systems!we!have! long]term!collaborations! with! organic! chemists! both! in]house! (Mårtensson,! Moth! Poulsen)! and!internationally!(Harry!Anderson!(Oxford),!Tom!Brown!(Oxford),!Atsuhiro!Osuka(Kyoto)).!!!About!15!PhD!students!have!graduated! from!the!group!many!of!which!today!either!holds!prominent!positions! in!the! industry!or!embarked!on!successful!careers! in!academia.!More!than! 120! papers! have! been! published! almost! exclusively! in! highly! ranked! journals.! Bo!Albinsson!was!Head!of!the!Department/Division!of!Chemistry!and!Biochemistry!(2006]2014)!and!is!today!Director!of!the!Nanoscience!and!Nanotechnology!Area!of!Advance!at!Chalmers!which! involves! some! 200! researchers! mainly! from! the! Physics,! Chemistry! and!Microtechnology! and! Nanoscience! departments.! He! is! often! recruited! as! evaluator! and!reviewer!both!nationally!and!internationally!and!has!recently!started!to!be!associated!editor!for!the!leading!Physical!Chemistry!Chemical!Physics!journal!(RSC).! !

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93!

Doctor*Elizabeth*Ball*Chalmers!University!of!Technology,!Sweden!!Elizabeth! Ball! earned! her! Ph.D.! in!Biology!at!The!University!of!York,!UK,!in! 1987.! She! continued! full]time!research! on! the! genetics! of! insect!flight! muscle! at! The! Johns! Hopkins!University,!USA!until!1989,!publishing!in! leading! journals! including! Cell,!before! combining! scientific! research!with! education! in! Athens,! Greece.! In!addition! to! teaching! and! examining!biology! for! the! International!Baccalaureate! for! more! than! twenty!years,! she! has! also! co]authored!several!text!books!and!toured!Greece!giving!public!lectures!on!science.!!

Since! 2007,! her! involvement! with!Molecular! Frontiers! has! included!promoting! the! Molecular! Frontiers!Inquiry! Prize! to! encourage! school!students! to!ask! scientifically! relevant!questions.! To! stimulate!discussions!about! science! in!our!everyday!lives,!she!has!brought!headline!news!to!teenagers!on!the!website!MoleClues!by!explaining!the!science!behind!the!news!items!in!simple!English,!with!an!additional!focus!on!why!the!news!is!important!and!how!the!research!was!conducted.!She!also!reaches!out!to!non]scientists;!having!personal!experience!of!the!strength!of!art!as!a!great!equalizer!among!people! of! all! backgrounds! and! ages,! she! considers! it! to! have! great! potential! in! attracting!young!minds!and!communicating!molecular!science.!By!developing!the!Molecular!Frontiers!Science@Art! website! to! communicate! with! non]scientists! using! art! as! a! medium! to! ask!scientific! questions,! she! continues! to! promote! scientific! ‘Curiosity,! creativity,! honesty,!knowledge’,!the!cornerstones!of!the!Molecular!Frontiers!Inquiry!Prize.!.! !

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94!

Professor*Barbara*Cannon*President!of!the!Royal!Swedish!Academy!of!Sciences!

Barbara! Cannon! took! a! B.Sc.! in! biochemistry! at!London! University! and! a! Ph.D.! in! physiology! at!Stockholm!University.!After!postdoctoral! studies!in!Ottawa,!she!returned!to!Stockholm!and!she!is!professor!of!physiology!there.!Already!during!her!doctoral! thesis,! she! studied! the! mechanism! of!uncoupling!of!brown!fat!mitochondria!as!a!model!system! to! understand! mitochondrial! energy!utilization.! Subsequently,! her! interests! turned!more!to!the!physiology!of!the!tissue,!concerning!both! molecular! and! integrative! aspects.! The!group! has! contributed! in! recent! years! to! noted!developments! in! the! field,! including! reviewing!radiology! literature! for! a!metabolic! audience! to!point! to! the! presence! of! active! brown! adipose!tissue! in! adult! man,! the! developmental!relationship! between! brown! adipocytes! and!myocytes,! the! requirement! for! keeping!mice! at!thermoneutral! environmental! temperatures! to!humanize!them,!and!the!induction!of!brown]like!adipocytes!in!classical!white!adipose!tissue!depots.!!

In! addition! to! and! in! parallel! with! her! scientific! achievements,! Cannon! has! and! has! had!numerous!honorary!appointments!nationally!and!internationally.!She!was!for!more!than!25!years!the!director!of!the!Wenner]Gren!Institute,!one!of!the!largest!institutes!in!the!science!faculty!at!Stockholm!University.!She!has!been!dean!of!biological!sciences,!and!she!is!and!has!been!a!member!of!a!large!number!of!biological!evaluation!committees,!both!in!Sweden!and!abroad.!She! is!an!honorary!doctor!at!Monash!University,!Melbourne,!the!Royal!Veterinary!College,! London! and! the! University! of! Buckingham.! She! has! been! a! fellow! of! the! Royal!Swedish!Academy!of! Sciences! since! 1989,! chairman!of! the!Academy's! biology! class! 2001]2003!and!vice]president!of! the!Academy!2003]2008.!She!was!Chairman!of! the!Trustees!of!the! Nobel! Foundation! from! 2009! ]! 2012.! She! is! a! recipient! of! the! King’s! Medal! (12th!magnitude)! in! the! band! of! the! Seraphim! Order.! She! is! currently! President! of! the! Royal!Swedish!Academy!of!Sciences.! !

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95!

Professor*Magdalena*Eriksson*Chalmers!University!of!Technology,!Sweden!!Prof.! Magdalena! Eriksson! is! currently! Adjunct!Professor!of!Medical!Biochemistry!at! the!School!of! Medical! Sciences! of! the! University! of! Cape!Coast! in! Ghana.! She! is! also! the! Director! of!Academic! Development! of! the! African! Institute!for! Mathematical! Sciences! (AIMS)! Global!Network.!!She! earned!her! PhD! in! Biophysical! Chemistry! at!Chalmers! University! in! Gothenburg,! Sweden! in!1988.! After! that! Prof.! Eriksson! continued! her!research!in!the!structure!and!function!of!nucleic!acids,! first! as! a! postdoctoral! fellow! at! Columbia!University!in!New!York!City!and!later!as!a!faculty!member! of! the! Department! of! Medical!Biophysics! of!Umeå!University! in! Sweden.! From!there!she!moved!to!the!Center!for!Biomolecular!Recognition! in! the! Department! of! Biochemistry,!University! of! Copenhagen,!Denmark.!During! her!time! there,! she! spent! sejours! as! a! visiting! scientist! at! Columbia! University! and! at! Sloan]Kettering!Institute!in!New!York!City.!!Prof.!Eriksson!enriched!her!competence!by!completing!a!Master’s!degree! in! journalism!at!Columbia!University! in! 2003.! In! the! following! year,! she! produced! science! television! news!pieces! and! continues! to!write! occasionally! as! a! freelancer.! She! also! served! as! a! research!manager! at! the! Juvenile!Diabetes! Research! Foundation.! In! 2008,! Prof.! Eriksson!moved! to!Cape!Coast,!Ghana,!where!she!joined!a!new!medical!faculty!as!Associate!Professor.!She!was!the! founding! head! of! the!Department! of!Medical! Biochemistry.! In! 2012,! she! became! the!first!Institute!Director!of!AIMS!Ghana,!which!opened!in!August!that!year.!After!a!maternity!leave!Prof.!Eriksson!returned!to!AIMS!as!the!Director!of!Academic!Development!for!its!fast!expanding!global!network!and!is!based!in!Sweden.!!Magdalena! is!on!the!board!of!Molecular!Frontiers!Foundation,!an!organization!she!helped!to!launch!in!2006!and!for!which!she!served!as!the!Executive!Vice!President!during!its!first!six!years.! Prof.! Eriksson! is! the!Nketesiaheema,! Queen!Mother! for! Young!Women,! of! Ekumfi!Edumafa,!a!fishing!community!on!the!Atlantic!shore!in!Ghana’s!Central!Region.!!! !

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96!

Professor*Andrew*Ewing*Chalmers!University!of!Technology,!Sweden! Andrew! Ewing! received! his! BS! degree! from! St.!Lawrence! University! and! a! PhD! from! Indiana!University.!After!a!postdoc!at! the!University!of!North!Carolina!he!joined!the!faculty!at!Penn!State!University!for!25!years,!where!he!had!been!Department!Head!in!Chemistry! (1999]2004)! and! J.! Lloyd! Huck! Chair! in!Natural! Sciences.! He! is! now! Professor! at! Chalmers!University! of! Technology! and! the! University! of!Gothenburg,!Sweden,!and!also!an!Honorary!Professor!at! both! Beijing! University! of! Science! and! Technology!and! Nanjing! University! of! Science! and! Technology,!China.!!!Focusing! on! the! neuronal! process! of! exocytosis,! his!group! has! pioneered! small]volume! chemical!measurements! at! single! cells,! electrochemical!detection! for! capillary! electrophoresis,! novel!approaches!for!electrochemical!imaging!of!single!cells,!and!new!electrochemical!strategies!to!separate!individual!nanometer!vesicles!from!cells!and!quantify!their!contents.!They!have!also!pioneered!the!development!and!application!of!mass!spectrometry! imaging! for! subcellular! and! neurochemical! analysis.! He! has! nearly! 300!publications! cited! approximately! 14500! times.! Recently,! he! has! received! the! Charles! N!Reilley! Award! from! the! Society! for! Electroanalytical! Chemistry,! the! American! Chemical!Society! Award! in! Electrochemistry,! the! Norblad]Ekstrand!Medal! of! the! Swedish! Chemical!Society,! and! the! SACP! Analytical! Chemistry! Award.! He! is! a! member! of! the! Gothenburg!Academy! of! Arts! and! Sciences! (2013)! and! the! Royal! Swedish! Academy! of! Sciences,!Chemistry!Class!(2012).!He!has!supervised!48!PhD’s!and!over!20!postdoctoral!associates.!* *

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97!

Professor*Fredrik*Höök*Chalmers!University!of!Technology,!Sweden!!Fredrik!Höök!obtained!his!Doctors!degree!of!Physics!in!1997!from!an!inter]disciplinary!PhD!program!between!the! Department! of! Applied! Physics! and! the!Department! of! Biochemistry! and! Biophysics! at!Chalmers! and! Gothenburg! University,! Gothenburg,!Sweden.! After! that! he! had! a! one! and! a! half! year!assistant! professor! position! in! surface! biotechnology!at!Cell!and!Molecular!Biology,!Gothenburg!University,!which! was! in! 2000! transferred! into! an! assistant!professor! position! in! Biological! Physics! at! the!Department!of!Applied!Physics!at!Chalmers.!In!2004!he!was!appointed!a!professor!position!in!Nanoscience!for!Biophysics! at! the! Department! of! Physics! at! Lund!University!and!in!2007!he!was!appointed!full!professor!in!Physics!at!Chalmers.!!His! research! has! focused! on! the! development! of!surface]based! bioanalytical! tools,! such! as! QCM]D,!localized!SPR!and!more! recently!TIRF!microscopy!and!imaging! ellipsometry! and! their! combination!with!microfluidics! for! fundamental! studies! of!cell]membrane!mimics! but! also! for! use! in! diagnostic,! drug]screening! applications! and! the!development!of!drug!delivery! concepts.! Efforts!are!presently! focused!on! (i)!new!methods!with! single!molecule! sensitivity! for! studies! of! single! liposomes! and! individual! membrane!proteins,! (ii)! microfluidic! platforms! for! detergent]free! separation! of! cell]membrane!components! and! (iii)! sophisticated! surface!modifications! and! nanofabrication! schemes! to!facilitate! improved! analysis! of! supported! cell]membrane!mimics,!membrane! proteins! and!virus!binding.!!Fredrik! Höök! is! presently! heading! the! Biological! Physics! division! at! Chalmers,! which! is!composed!of!around!20!scientists!on!various!levels.!He!has!published!around!130!scientific!papers,!has!an!H]index!of!42,!with!20!papers!cited!more!than!100!times!and!more!than!7000!citations! in! total.! He! is! also! co]founder! of! the! companies! Q]Sense! AB,! LayerLab! AB! and!Gothenburg! Sensor! Devices! AB.! He! has! been! awarded! the! Akzo! Nobels! Nordic! research!award!in!2002,!an!individual!grant!for!the!Advancement!of!Research!Leaders!and!in!2005!by!the!Swedish!Foundation!for!Strategic!Research!and!the!prestigious!Göran!Gustafsson!prize!in!Physics!in!2012!by!the!Royal!Swedish!Academy!of!Sciences.!

* *

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98!

Professor*Karin*Markides*Chalmers!University!of!Technology,!Sweden!!Karin!Markides! is! President! and! CEO! of! Chalmers!University!of!Technology!since!August!2006.!!!Karin!Markides,! professor! of! analytical! chemistry,!previously! taught! and! conducted! research! at!Stockholm! University,! Brigham! Young! University,!USA!and!Uppsala!University.!As!part!of!her!broad!international! experience,! she! held! a! guest!professorship! at! Stanford! University! in! the! US.!Karin!Markides! is!a!member!of!The!Royal!Swedish!Academy! of! Sciences! and! member! of! The! Royal!Swedish! Academy! of! Engineering! Sciences.!!!Prof.! Markides! was! recently! Chairman! of! CESAR!(The!Conference!of!European!Schools!for!Advanced!Engineering! Education! and! Research)! for! a! three!year! term.! She! has! also! recently! completed! her!term!as!Chairman!of!UNITECH!International!Society!(student! exchange! programme/community! that!develop!leadership!skills!while!connecting!companies!and!academia).! !

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99!

Professor*Aleksandar*Matic*Chalmers!University!of!Technology,!Sweden!

!

Aleksandar! Matic! is! a! professor! of! physics! at!

Chalmers! University! of! Technology! He! received!

his! MSc! degree! in! engineering! physics! from!

Uppsala! University! and! his! PhD! degree! from!

Chalmers!University!of!Technology.!Following!the!

PhD! he! worked! for! the! establishment! of! the!

European! Spallation! Source! (ESS),! the! Europe’s!

next! generation! neutron! source,! in! Scandinavia!

and! Sweden! before! returning! to! Chalmers! as!

assistant!professor.!He!became!professor!in!2010!

at! the!Department! of! Applied! Physics! and! since!

2011!he!holds! a! senior! researcher!position!with!

the! Swedish! Research! Council.! He! is! today! the!

director!of!Chalmers!Area!of!Advanced!Materials!

Science.!

!!

His! research! interest! is! direct! towards! soft!

matter! and! energy! applications.! A!major! theme!

for!his! research!group!new!electrolytes,!based!on!polymer!membranes!and!colloidal! gels,!

for! Li]metal,! Li]ion! and! Li]Sulfur! batteries.! The! work! also! includes! investigating! the!

compatibility! and! influence! of! the! electrolytes! with! Li]metal! anodes! and! with! new!

nanostructured!carbon]sulfur!composite!cathodes!for!Li]Sulfur!batteries.!A!particular!focus!

is!the!use!of! ionic! liquids! in!different!types!Li]batteries,!where!transport!properties,!phase!

behavior,! ion! interactions!and!polysulfide!speciation.!The!aim! is! to!determine!the!relation!

between! microscopic! structure! and! interactions,! using! a! combination! of! spectroscopic!

methods,!to!macroscopic!properties!and!the!functionality!of!the!electrolyte!in!the!battery.! !

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100!

Doctor*Deborah*Donnelly*McLay*Chalmers!University!of!Technology,!Sweden!

Deborah!Donnelly]McLay!has!been!involved!in!the!aviation!industry!for!over!25!years.!She!is!currently!an! international! Boeing! 767! airline! pilot! with!United! Parcel! Service.! Her! background! and!experience! in!aviation! include!many!diverse! roles,!including:! FAA! Certified! Flight! and! Ground!Instructor,! FAA! Certified! Check! Airman,! Flight!Simulator! Instructor,! Flight! Engineer,! LOSA!Observer!and!Airline!Transport!Pilot.!Deborah!was!also!nominated!as!the!Crewmember!of!the!Year!in!2013!at!UPS.!

Deborah! has! been! volunteering! with! Molecular!Frontier!since!2010.!Deborah!has!collaborated!with!Rotary! International! for! the! past! few! years! and!sponsored! students! from! the! United! States! to!attend!the!Molecular!Frontiers!Annual!Symposium!in!Stockholm.!Deborah!enjoys!serving!as!a!mentor!for!the!students!and!collaborating!with!the!annual!Molecular!Frontiers!Inquiry!Prize!and!getting!students!involved.!!

Deborah! has! earned! a! Master’s! Degree! in! Aeronautical! Science! from! Embry! Riddle!Aeronautical! University.! She! is! currently! terminating! a! second! Master’s! Degree! from!Harvard!University!and!a!Doctorate!in!Education!this!year.!!

In!addition!to!flying,!Deborah!continues!to!have!a!passion!for!teaching!and!education.!She!is!currently! an! Associate! Professor! of! Aeronautics! at! Embry! Riddle! Aeronautical! University!Worldwide! and! at! Everglades! University,! teaching! both! graduate! and! undergraduate!courses!in!Aeronautical!Science.!Deborah!has!also!served!as!a!SME!in!STEM!curriculum.!

Deborah!has!collaborated!with!Harvard!University!and!help!create!the!Pilot!Health!Survey.!As! the! Project! Manager,! Deborah! hopes! to! create! awareness! for! airline! pilots! of! the!environmental! issues! that! affect! this! unique! population! and! their! health,! in! the! cockpit!environment!and!help!future!generations!of!aviation!professionals.!!

Deborah! is!currently! the!Area!Governor! for!Rotary! International!District!6930,! since!2012,!and! has! also! served! as! the! President! of! the! Boynton! Beach/Lantana! Rotary! Club! for! two!terms.!Deborah!is!very!involved!with!education!and!programs!to!promote!STEM!to!students!and! volunteering! in! her! community.!Additionally,!Deborah!belongs! to!Women! in!Aviation!International!and! represents!UPS!at! the!annual! conference.!Deborah! is! the!Treasurer!and!Past!Chairman!of!the!Board!at!the!YMCA!of!South!Palm!Beach!County.!

* *

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Professor*Jens*Nielsen*Chalmers!University!of!Technology,!Sweden!!Jens! Nielsen! has! an! MSc! degree! in! Chemical!Engineering! and! a! PhD! degree! (1989)! in!Biochemical!Engineering!from!the!Danish!Technical!University! (DTU),! and! after! that! established! his!independent! research! group! and! was! appointed!full! Professor! there! in! 1998.! He! was! Fulbright!visiting!professor!at!MIT! in!1995]1996.!At!DTU!he!founded! and! directed! Center! for! Microbial!Biotechnology.!!!In!2008!he!was!recruited!as!Professor!and!Director!to! Chalmers! University! of! Technology,! Sweden,!where!he!is!currently!directing!a!research!group!of!more!than!50!people!and!the!Life!Science!Area!of!Advance,!which! coordinates! over! 200! researchers!from!5!departments.!Jens!Nielsen!has!published!so!far!more!than!450!research!papers!that!have!been!cited!more!than!15,000!times!(current!H]factor!59),!co]authored! more! than! 40! books! and! he! is!inventor!of!more!than!50!patents.!He!has!founded!several!companies!that!have!raised!more!than! 25!million!€! in! venture! capital.! He! has! received! numerous! Danish! and! international!awards!and!is!member!of!the!National!Academy!of!Engineering! in!USA,!the!Royal!Swedish!Academy!of!Science,!the!Royal!Danish!Academy!of!Science!and!Letters,! the!Royal!Swedish!Academy! of! Engineering! Sciences,! the! American! Academy! of! Microbiology,! Academy! of!Technical! Sciences! in!Denmark,! the!Royal! Society!of!Arts!and!Sciences! in!Gothenburg!and!the!American!Institute!for!Medical!and!Biological!Engineering.!He!is!a!founding!president!of!the!International!Metabolic!Engineering!Society.!* *

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Professor*Bengt*Nordén*Chalmers!University!of!Technology,!Sweden!!

Bengt!Nordén!is!since!37!years!Chair!Professor!of!Physical! Chemistry!at! Chalmers.! He! has! a! keen!interest! in! fundamental! physical! and! chemical!sciences,!universally,!and!a!particular!curiosity!in!light]matter! interactions.!For!many!years!he!has!exploited!polarized!light,!in!a!variety!of!ways,!for!diagnosing! interactions! of! small! molecules! with!bio]macromolecules,! such! as!DNA.! It!was! either!chiral!effects,!probed!by!circularly!polarized!light,!or! macroscopic! orientation! effects,! probed! by!linearly! polarized! light.! Based! on! results! from!such!studies!he!contributed!to!the!development!of! several! new! DNA]recognizing! ligands,!including! substitution]robust! chiral! transition!metal! compounds,! bis]intercalators! and! peptide!nucleic! acids! (PNA).! He! has! introduced! several!new! concepts,! such! as! “hydrophobic! catalysis”,!“phase! shift! catalysis”! and! “kinetic! recognition”!and! demonstrated! how! they! can! explain! various! peculiar! bio]macromolecular! reactions.!More! recently! he! has! been! involved! in! single]molecule! studies! of! stretched!DNA! and! the!possible!role!of!stretched!DNA!conformations!in!the!mechanism!of!homologous!recognition!and!genetic!recombination!as!mediated!by!bacterial!and!human!recombinases.!

Bengt! has! had! many! national! as! well! as! international! commissions! of! trust,! including! as!Chair! of! the! Nobel! Committee! for! Chemistry,! and! Chair! of! the! Chemistry! section! of! the!Swedish! Research! Council.! He! was! in! 2006! the! Chairman! of! of! CERC3! (Chairmen! of! the!European!Research!Councils’!Chemistry!Committees)!and!then!initiated!a!new!organization,!“Molecular! Frontiers”,! with! the! two]fold! purpose! of! both! early! identifying! scientific!breakthrough!as!well!as!making!society,!in!particular!youth,!interested!in!science!and!show!that!science!is!indeed!very!useful.!One!inspiration!was!the!Nobel!Centennial!Symposium!he!organized!in!2001!on!"Frontiers!of!Molecular!Science"!–!many!speakers!of!which!now!being!members!of!the!Scientific!Advisory!Board!of!Molecular!Frontiers.!!

Bengt!has!been! recognized!by!many!academy!memberships!and!honorary!positions,!most!recently!an!Honorary!Degree!at!Nanyang!Technology!University!conferred!to!him!last!year!by! the! President! of! the! Republic! of! Singapore! and! an! Honorary! Fellowship! by! the! Royal!Society!of!Chemistry!of!UK.!! !

!

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Doctor*Per*Thorén*Chalmers!University!of!Technology,!Sweden!

!

Per! Thorén! is! Chief! Operating! Officer! (COO)! of!

Molecular! Frontiers! and! has! served! as! project!

manager!and!web!editor!for!the!organization!since!it!

was! formed! in!2006.! !He!has!planned!and! launched!

MoleClues,! a! web! site! for! young! people! to! explore!the!world!of!molecules.!Through!games,!videos!and!

other!activities,!MoleClues!seeks!to!inspire!curiosity,!

spread!knowledge!and!show!how!scientific!discovery!

is! done.! Thorén! is! particularly! passionate! about!

reaching! out! to! those! who! are! NOT! already!

interested!in!science,!aiming!for!a!long]term!change!

in! attitude.! He! has! a! broad! experience! in! teaching,!

ranging!from!7!year!olds!to!university!students.!

!

Thorén! has! a! PhD! in! physical! chemistry! from!

Chalmers! University! of! Technology,! studying! cell]

penetrating! peptides! for! the! delivery! of! gene]

targeted! drugs.! He! has! also! worked! for!

pharmaceutical!company!AstraZeneca,!characterizing!surfactants!for!solubilization!of!poorly!

soluble!drugs.!

!

Thorén! is! behind! numerous! science! outreach! projects,! including! the! award]winning! film!

series! The# Chemistry# Calendar! (Kemikalendern),! the! widespread! online! competition!

Kemikampen,! the! annual! exhibition!Materials# in# our# daily# lives! as! well! as! many! popular!

activities! in! the!Gothenburg!Science!Festival.!He!also!works!as!communications!officer! for!

the! Materials! Science! Area! of! Advance! at! Chalmers,! organizing! the! annual! conference!

Materials#for#Tomorrow,!and!is!heavily! involved!in!Chalmers!newly!started!initiative! in!the!

field!of!sports!technology.!

! !

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Professor*Anders*Ådahl*Chalmers!University!of!Technology,!Sweden!!Anders! Ådahl! is! director! of! the! Chalmers!Energy!Area! of! Advance! (AoA).! He! has! been!engaged!in!the!Swedish!and!European!energy!debate!the!last!15!years,!both!from!industrial!and! academic! positions.! His! specialties!relates! to! energy! systems! analysis,! energy!technology!assessment,! energy! markets!analysis! and! policy! to! the! energy!sector.!Research! funding! and! diffusion! of!knowledge!are!other!areas!of!expertise.!!The!broad!overview!of!the!many!different!aspects!on!energy!is!maybe!his!main!specialty.!!!Currently! Anders! Ådahl! is,! besides! many!Chalmers! related!engagements,! chairman! of!the! board! of! Elforsk,! member! of! the! EU!Horizon! 2020! Advisory! Board! on! Energy! to!the$ Commission,! Reference' Group' Member'to# the# Swedish!National! Reference! group! to!Horizon!2020!]!Energy,!Chairman!of!Din!El!environmental!fund,!board!member!G!Engströms!ABB]foundation.!He!is!often!engaged!as!invited!speaker!or!moderator. !!!He! holds! an!MSc! in! Chemical! Engineering! (1998),! a! PhD! in! Energy! and! Environmental!Science!(2004)!and!is!professionally!trained!in!leadership.!Before!Anders!Ådahl!joined!Chalmers!in!2012!he!held!different!positions!at!Göteborg!Energi!AB!such!as!Energy!Systems!Analyst,!head!of!Research!and!Development,!and!project!leader!of!reorganization!of!the!company.!Previous! engagements! are! Working! Group! Member! to! the! Swedish! Smart! Grid! Council,!Head!of!Elforks!program!board!on!Energy!Market!Research,!member!Elfork!program!board!on!Energy!Systems!Research,!Member!of!the!Board!of!Johanneberg!Science!Park,!Member!of! the!Board!of!Hydrogen!Sweden,!Member!of! the!Board!of! ETC!battery! research! centre,!Member!of! the!Board!Göteborg!Energi! research! foundation,!Member!Eurelectric!Working!Group!Prospective!(Swedish!representative).!!!Anders! Ådahl! is! as! director! the! Chalmers! Energy! AoA! focusing! on! strengthen! energy!research! within! Chalmers! and! making! science! useful! to! the! industrial! and! public! sector.!Creating! links! between! fundamental! and! applied! science,! integrating! knowledge! from!different! scientific! fields,! and! offering! arenas! for! mutual! knowledge! exchange! between!academia! and! industry/society! are! some! of! the! important! tools.! Transformation! of! the!energy! systems! towards!a!more! sustainable! future!via! science!and!knowledge!diffusion! is!Anders!Ådahls!main!driving!force.!

Molecular FroNtiers · 2019. 7. 29. · ! 3!...

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