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PartIIIBiologicalPhysicscourse- 2020Lecturer: Dr DianaFuscodf390

Prof.PietroCicuta

Supervisions:NikhilKrishnannpk28

Guestlectures:

Dr.JamieBlundell(Oncology)Dr.Somenath Bakshi (Engineering)Prof.BenSimons(DAMTP)Dr.JamesLocke(SainsburyLab)

PhysicalBiologyoftheCell- 2nd ed.,Garland2013Phillips,Kondev,Theriot,GarciaReadinglist:

ModelsofLife- CUP2014&freee-bookKimSneppen

PhysicsinMolecularBiology- CUP2005KimSneppenandGiovanniZocchi

PartIIThermalStatisticalPartIISoftCondensedMatter[orselfstudy]

Pre-requisites:

AnIntroductiontoSystemsBiology- ChapmanandHall2007+2nd ed 2020UriAlon

PhysicalModelsofLivingSystems- Freeman2015

BiologicalPhysics- :Energy,Information,Life- Freeman2007

PhilNelson

MolecularBiologyoftheCell- Garland(manyeditions,updatedalmostyearly)BruceAlbertsetal.

Warning,thisisabiologybook

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UsefulInformation:Website,linkedfromTiS:http://people.bss.phy.cam.ac.uk/courses/biolectures/

Sendcomments&errorstodf390.Alistofknownerrorsismaintainedonthewebsite.

SupervisionsavailableforstudentsinPartIIIandMASt(3supervisions, 1or2largegroups,SmallLectureTheatre).

Times(TBD,butapproximatelyevery2-3modules)

Wewillprovidewrittenanswerstothequestionsheetattheendofthecourse.

Structureofthecourse:24lectures,in7modules:

A- context/overview/intro/basics,networksB- evolutionandgrowthofpopulationsC- dynamicsinthecellD- elementsofneuro-physicsE- patternformationinbiologyF- proteinproductionandregulationofgeneexpressionG- dynamicalsystems,switchesandoscillations

4lectureswillbegivenbyotherCambridgecolleaguesactiveonthebiology/physicsinterface:materialclosertoactiveresearch(detailsnotexaminable)

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Lengthscales

BiologicalsystemshaveahierarchicalorganizationacrossmanylengthscalesLengthscaleßà Timescale…hence“emergence”.Non-equilibrium(butconsideringseparationoftimescales,equilibriumoftenvalid)Selfassemblyandselfreplication

Wefocusinthiscourseonscaleswherethermalnoiseandsmallnumbernoiseareatplay- classicalstatisticalmechanics.

e.g.photosynthesis e.g.ecologicalsystemsandevolution

Ourcourse

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Whyisitagoodtimeto“deploy&develop”physicshere?

Fantasticdetailedknowledgeofthemoleculesthatmakeuplivingsystemsfromdecadesof“structuralbiology”.Precisegeneticcode.Thebroadlycorrectunderstandingofmechanismsofactionofmanyoftheseconstituents.Quantitativedatasetsresolvedonrelevantlengths&times.Uniquepowerofphysics (statmech,dynamicalsystems,softmatter)inlinkingupscalesàmodelsthathavethe“correct”mechanism,andthatrepresentanunderstanding. Physicsisrequired.

e.g.photosynthesis e.g.ecologicalsystemsandevolution

Ourcourse

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Physicsisrequired.Asinotherfields(condensedmatter,etc),whatisourapproach?

• Understandcontext- here,cellbiologycontext.• Makeorderofmagnitudeestimates.• Becomefamiliarwithtoolsformodelbuilding.• Criticalanalysistodeterminelimitations,andsuggestrefinement

tomodels.

Crick’slegacy- PolymerLanguages

Hierarchyofscales:bothInformationandStructure. 8lecture 1

Structure

Spaceof“Genotypes”

Spaceof“Phenotypes”

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Generegulation:the“centraldogma”Crick1953-1957

NucleotidesandDNA

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AdenineThymineGuanineCytosine

ReplacedbyUracilinRNA

Thegeneticcode

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ManywaystoseeaDNAdoublehelix

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Manywaystoseeaprotein

13lecture 1

Manywaystoseealipidmembrane

14lecture 1

Tocells:Manywaystoseeabacterium

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Whatis“right”levelofdescription?

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Whatdowewanttoavoid?

Exampleofpopulationgrowthdata

f(t)=a1/[a2– (t/1yr)]a1=10000,a2=2050worksverywellorf(t)=a1exp(a2t)

PhysicalModelsneedtoreflectamechanism,andcanpointustofurtherkeyinsights. 17lecture 1

Asuccessinquantitativebiology(andstillongoing):TheLacrepressorWhereStatmech andPolymerphysicsmeetthebiologyofgeneregulation

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Anexampleof“importantquestion”thatcanbeaddressedinverydifferentways:Howdocellsregulatedivisiontohaveameansize?

Inprinciple,controlcouldbethrough“sizer”,“timer”orsomecombination.

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E.colibacteriaImagedinfluorescencemicroscopy.

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FromS.Jun, S.Taheri-Araghi,TrendsinMicrobiology4,23(2015)

Dataonregulationofdivision

Howdocellsregulatedivisiontohaveameansize?Onecanalsotrytoestablishthegeneralcontroltheory,lookingatthedata.

Onecansearchforthemolecularmechanism,butcertainlymorecomplexthan“thegene”!Notsosimpletocomeupwithsizermechanisms:plausiblescenarioputforwardinyeastmightinvolvesensingsizethroughthebalancebetweenaspeciesthathasconstantconcentrationinthecellvolumeasmonomers,anadsorptionequilibriumwiththemembrane(hence#proptoarea),andapolymerisation“sink”.Concentrationatthesinkisthenamembraneareasensor,triggeringdivision.23

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Recap:- Spiritandremitofthiscourse.- Howphysicscontributestothis

areaofscience.- Afirstoverviewofcellmachinery.- Confidenceindevelopingmodels

anddeterminingtherightlevelofdescription.

- Nexttwolecturesare“intro”tonetworks.