EMV Newsletter OCTOBER 2012. EDITOR: ANNA.APPELBERG@MED.LU.SE

© Michiko Mori

CONGRATULATIONSCongratulation Mauno Vihinen who is now officially installed

as a Lund University professor. Congratulations Laurent Roy-

bon to your 300 000 SEK from Jeansson’s foundation.

INFO ON THE NEW ANIMAL DIRECTIVESAs of Jan 1st there are new directives governing research

animals. A summary can be found if you click here (Swedish).

Jordbruksverket, the Swedish Board of Agriculture, visits us

in Belfragesalen Dec 13th 13:30-16:30 to inform.

PERSONNEL PLANS FOR TEACHING STAFFAll teachers and teaching staff at EMV are kindly asked to

hand in a personnel plan for 2013 by Nov 1st. See e-mail

from Oct 24th.

SAFETY-INSPECTION DATESNext up is Tues Nov 13th is B12 and B13. Tues Dec 11th it’s

B14 and C11. Click here for inspection times on your floor.

LU LIMITS SUPPORT FOR OPEN-ACCESS PUBLICATIONSo far, LU has sponsored 100% of the publication fee for

so called pure Open Access publications (i e PLoS, BioMed

Central, Hindawi). As of Nov 1st LU will sposor 50%. Click

here for more info.

LUND UNIVERSITY IMMUNOLOGY SEMINAR SERIES”IL-23 in autoimmunity: The location matters” Prof. Burk-

hard Becher, Zürich. Mon Oct 29th, 15–16, Segerfalksalen.

SVERIGES UNGA AKADEMI SÖKER LEDAMÖTER En tvärvetenskapligt forskningspolitisk plattform grundat av

KVA. Läs mer på www.sverigesungaakademi.se

EDUROAM (education roaming)

A secure, world-wide roaming access service that allows LU

staff to reach internet across campus and when visiting other

universities by simply opening the laptop. www.eduroam.org

Click here for LDC’s set-up instructions.

ERIC KANDEL YOUNG NEUROSCIENTISTS PRIZE Candidates must be nominated by the head of their research

institution or by an internationally outstanding neurosci-

entists. Submission deadline 1st Nov. The prize (overall €

75,000) will be awarded officially in the second half of 2013

in Frankfurt.

PARKINSON RESEARCH FOUNDATION Up to 1 000 000 SEK for research on curing or mitigating PD

and other neurodegenerative diseases. Applicant must have

a PhD from a Swedish university. Deadline: Nov 30th. Junior

applicants prioritized.

GELIN SCHOLARSHIPS A total of SEK 100 000 for clinical researchers in the trans-

plantation field. Application deadline: Nov 2nd.

THUREUS FOUNDATION FOR GERIATRIC RESEARCH A total of SEK 634 000 for geriatric research. Application

deadline Nov 30th.

2 NEWSLETTER FOR THE DEPARTMENT OF EXPERIMENTAL MEDICAL SCIENCE

Changes in the Postgraduate Education

It’s a great pleasure and privilege to have the opportunity to work with research-education at EMV meeting all our friendly and ambitious PhD students and their supervisors. Gladly, we have a steady inflow of new PhD students to the Department substituting for the “old ones” successfully defending their thesis. The theses presented by our PhD students are of very high quality. Importantly, the PhD student-period provides an opportunity for the student to gain insight in the research process including joys and pitfalls in the publication process, although there is some time ahead for all graduated PhD students before they become fully experienced researchers. Once again, our students and supervisors and their milieus do a fantastic job. Undoubtedly, it’s a great challenge and an important task for the Universities, but also for the community as a whole, to utilize and take care of these well-educated PhD students as they graduate. They represent a fantastic resource.

For PhD students accepted by January 1st, 2012, the qualifications for presenting a doctoral thesis, in terms of number of publications and manuscripts, are changed according to the text in the left-hand fact box. Click here to visit the faculty info pages. An English translation is found on page 6 in this newsletter.

Importantly, the text indicates that the Department and the Faculty are well aware that not only the number of papers but also their quality and impact should be taken into consideration. Additio-nally, the involvement and responsibility of the PhD student in the underlying experiments, planning, writing etc. is taken into consideration by the Department and the Faculty as they evaluate and judge the application for dissertation. Finally, I recommend strongly all our PhD students to keep record of your achievements concerning teaching, conferences, courses etc., i.e. update regularly your portfolios.

The PhD students play important roles in many aspects of research and teaching at EMV and they will certainly continue to do so also in the future.

Bengt-Olof Nilsson, Head of the Postgraduate Education

Photo: K Ruona

“Normen för en sammanfattningsavhandling

för doktorander antagna efter 1 jan 2012 är

fyra arbeten. Av dessa ska två arbeten vara

publicerade eller accepterade varav minst ett där

doktoranden är ensam försteförfattare. Färre

antal delarbeten kan accepteras om delarbetena

kan bedömas vara av mycket hög kvalitet eller

innehåller viktig metodutveckling utförd av

doktoranden, vilket ska framgå av huvudhandle-

darutlåtandet. Disputation kan avstyrkas trots

att avhandlingen uppfyller dessa formella krav

men inte håller tillräckligt hög kvalitet. Ett enskilt

arbete bör inte ingå i mer än två avhandlingar.”

3QUOUSQUE TANDEM ABUTERE

NEW RESEARCH GROUPS AT EMV PRESENT THEMSELVES AND THEIR SCIENCE

IN FERNSTRÖMSALEN 14-17. DINNER AT STAMSTÄLLET AFTERWARDS.

MAUNO VIHINEN’S GROUP - PROTEIN BIOINFORMATICS

KARIN LINDKVIST’S GROUP - MEDICAL STRUCTURAL BIOLOGY

JENS LAGERSTEDT’S GROUP - MEDICAL PROTEIN SCIENCE

ROGER OLSSON’S GROUP - CHEMICAL BIOLOGY AND DRUG DISCOVERY

GUNNAR GOURAS’S GROUP - EXPERIMENTAL DEMENTIA RESEARCH

LENA SVENSSON’S GROUP - LEUKOCYTE MIGRATION

Ever

yone welc

ome!

Sign up before Th

ursday: http

://tinyu

rl.com/EM

VESD

Experimental Science DayNOV 8TH - A COMEBACK OF THE POPULAR 2009 SEMINAR SERIES

”EMV-DAGEN”

Photo: K Ruona

4 NEWSLETTER FOR THE DEPARTMENT OF EXPERIMENTAL MEDICAL SCIENCE

Fredrik Leeb-Lundberg worked with Nobel prize lau-reates Robert Lefkowitz and Brian Kobilka between -82 and -86. Lefkowitz and Kobilka are awarded the chemistry prize for their studies of G protein–coup-led receptors.

AS A PROFESSOR AT A SWEDISH UNIVERSITY YOU ARE INVITED TO NOMINATE CANDIDATES FOR THE NOBEL PRIZE. HAVE YOU EVER DONE THAT? ”I have nominated Bob once or twice.” It’s one pm.

I’ve stopped by Fredrik Leeb-Lundberg’s office. He is preparing a lecture for

a conference in London and has a number of explanatory illustrations ready

right at his powerpoint fingertips.

”They are called G protein-coupled receptors for historic reasons,” Fredrik

starts out. ”After a while one figured out that they can signal independent of

G proteins. Nowadays they are also called `seven transmembrane receptors

or 7TM receptors´ because they cross the cell membrane seven times.” He

motions to a slide with a representation of a receptor. It reminds me of a ball

of tagliatelle floating on a water surface.

There are between 800 and 900 G protein-coupled receptor types in humans.

About half of them are located in the nose and the sense of smell. Linda

Buck and Richard Axel were awarded the Nobel prize in Medicine in 2004 for

their work on the olfactory system. In 1988 Sir James Black was awarded the

prize for the heart-medicine beta-blockers, also targeting G protein-coupled

receptors.

”These receptors are the basis for most pharmacology as we know it,” Fredrik

says. ”Up to 50% of the drugs in a pharmacy target G protein-coupled recep-

tors. Therefore they represent a vast source of potential new drug targets.”

According to Fredrik, who has got phone calls from the local paper as well as

national news giant Svenska Dagbladet, many people question why Lefkowitz

and Kobilka were awarded the prize in chemistry and not medicine.

”I think there had been a feeling that these discoveries had to be recognized,” Fredrik speculates. ”But the research,

although very physiological, isn’t necessarily very translational. They often want something more like `there, we’ve

cured this or that disease´. I think the committees talk to each other and that, thanks to the `medicinal-chemical´ aspects

and the discovery of methods to obtain a detailed molecular map of very complex and flexible membrane proteins,

they accommodated the discoveries under the chemistry prize umbrella.” Fredrik says the G protein-coupled receptors

bind everything from ions, lipids and amino acids to peptides and even viruses. He gives the big, bad HIV-virus as

one example.

Fredrik Leeb-Lundberg is well connected

Lefkowitz ’s lab in 1983. Fredrik Lundberg second man standing from the left. Robert ”Bob” Lefkowitz is the man wearing glasses in the back row on the right. Brian Kobilka is yet to join the lab.

5NEWSLETTER FOR THE DEPARTMENT OF EXPERIMENTAL MEDICAL SCIENCE

CAN YOU GIVE US A FEEL FOR THE TIME IN LEFKOWITZ’S LAB? ”In 1982 I was working in his lab as a post doc. I stood at the bench and purified a G protein-coupled receptor for

adrenaline. Lefkowitz’s first intention was to try to figure out how adrenaline signals to the cell. This laid the ground-

work for many subsequent major methodological breakthroughs. Cell signaling was more or less a black box. I was so

excited. I had recently moved from California and Laguna Beach where I had learned how to surf and met my wife. I was

adjusting to Duke University and east-coast mentality. At work we were doing cool, new stuff and really sophisticated

biochemistry. Brian Koblika is two years younger than I and our post doc periods partially overlapped. In 1986 I left for

a position at University of Texas, and in 1989 he left for a position at Stanford.”

Fredrik remembers the Lefkowitz and Kobilka from thirty years ago as two somewhat egocentric very determined and

focused go-getters. In retrospect, it is clear that the work they have done required single-mindedness. ”Kobilka put his

mind to that he would crystallize a receptor structure.” What would he gain by that? ”Purifying the receptor, all you

can see is a dot on a gel. Crystallizing membrane proteins in general is hard, and it’s even harder when they cross the

cell membrane seven times with very flexible connecting loops.” Fredrik explains that knowing the exact conformations

of a receptor, as well as the differences between various receptors, enables researchers to engineer ligands and fine-

tune the desired signal outcome. One can compare the crystallization process with wanting to take a snap shot of the

receptor structure without the cell membrane’s surrounding lipids; the glitch being that without the lipids, the receptor

structure falls apart. It took Lefkowitz 10 years to purify the receptors and Kobilka 13-14 years to crystallize them.

”With research you tend to look back and ask yourself `was that really anything´? But each discovery is a building

block for the next. Where we are today is always only the beginning. Our early work led to obtaining protein sequence

”Kobilka will come here. He said yes.”information, which led to cloning of the receptor, which led to systems that

could express sufficient receptor quantities for crystallization.” As for begin-

nings, Fredrik became a professor and ended up staying 25 years in the States.

He was back between 2009 and 2011 to help his former university set up

an institute.

WHAT’S NEXT FOR YOU TO DO? ”Now we need to link conformational receptor states to specific functions.

Also, there are still several G protein-coupled receptors that we call `orphans´.

That means that the receptor is familiar, but the ligand, or stimuli, is yet to

be discovered. One of them is `GPR30´.” Isn’t that an estrogen receptor that

Anders Holm and Bengt-Olof Nilsson have worked on?” Yes. It’s really nice

to work with them. The receptor is affected by estrogen, but I think there’s

another natural ligand. I have high hopes for this receptor; it seems to be

involved in breast cancer, cardiovascular regulation and insulin release.

A LAUREATE ON THE LEEB-LUNDBERG COUCH?Before I leave, Fredrik has a surprise in stall for me: Collaborating with

the university’s chemistry association he has pulled some strings: “Kobilka

will come here.” Now? In December!? ”He said yes. I think the Nobel

foundation has the final say about his schedule, but he gave a preliminary

yes. I hope Lefkowitz will agree to come too.”

Fredrik demonstrates a receptor model he inherited from constructor professor Christer Owman. ”The ligands bind with an incredible affinity, so neither the receptor or ligand concentration need to be very high. That also make the receptors difficult to work with in natural systems.”

DISSERTATIONFor PhD students accepted after Jan 1st 2012 the thesis should include four papers. Two of these should be

published or accepted for publication, and one of these two

should have the PhD student as sole first author. The thesis

may comprise fewer than four papers if these are considered

to be of very high quality, or contain method development

by the PhD student. The supervisor’s testimonial has to ac-

count for this. A dissertation can be rejected despite the fact

that these requirements are met, if the thesis does not mea-

sure up quality-wise. It is not adviseable for a single paper to

be part of more than two theses.

Svenska“Normen för en sammanfattningsavhandling för doktorander

antagna efter 1 jan 2012 är fyra arbeten. Av dessa ska två

arbeten vara publicerade eller accepterade varav minst ett

där doktoranden är ensam försteförfattare. Färre antal delar-

beten kan accepteras om delarbetena kan bedömas vara av

mycket hög kvalitet eller innehåller viktig metodutveckling

utförd av doktoranden, vilket ska framgå av huvudhandleda-

rutlåtandet. Disputation kan avstyrkas trots att avhandlingen

uppfyller dessa formella krav men inte håller tillräckligt hög

kvalitet. Ett enskilt arbete bör inte ingå i mer än två avhan-

dlingar.”

HALF-TIME EXCEPTIONBecause of the high number of applicants, the Research

Ethics and Oral Communication courses may nowadays also

be completed after the half time.

PORTFOLIOThe portfolio is mandatory. For PhD students accepted af-ter Jan 1st 2012 it is worth 12 hp. There’s a new webtool

for the portfolio: ”Mahara”. Log in with your lucat-ID.

PhD NewsFOR STUDENTS ACCEPTED AFTER 12-01-01

Photo: Kennet Ruona

ANNA-LISA ROSENBERG SCHOLARSHIPUp to 100 000 sek for research on diseases of the

nervous system. Not for travelling or for applicant’s

own salary. Applicants holding a PhD and being

in the early stage of their career are prioritized.

Projects should preferably be carried out within the

neurobiological field and involve clinical collabora-

tion - having a co-applicant from a clinical section is

beneficial.

Send application to Anna Appelberg EMV:s kansli Hs

66 BMC I13. Application should arrive no later than

09:15 Monday Nov 5th.

The application can be in Swedish or English and

should contain:

• Project title

• Title, position and working place of applicant

(and co-applicant)

• Short résumé (”CV”) and publication list of app-

licant

• Specified project costs

• List of other grants awarded or applied for by the

particular project.

• Account of any previous grant awarded by the

Anna-Lisa Rosenberg Foundation

• Project summary of maximum 300 words

• Project plan with explicit focus (not more than

4 pages, including illustrations and references)

• Go-ahead from animal testing committee

PROLONGED DEADLINE: MONDAY NOV 5TH!

Anna-Lisa Rosenberg

NEWSLETTER FOR THE DEPARTMENT OF EXPERIMENTAL MEDICAL SCIENCE

Mahara DemonstrationNov 1st 9-11 GK-salen

Please click here to register.

7QUOUSQUE TANDEM ABUTERE

IF DEALS CLOSED BY LUND UNIVERSITY ARE NOT RESPECTED, YOUR RESEARCH GROUP (!) RISKS BEING FINED FOR CONTRACT BREACHING OR ”AVTALSBROTT”.

GENERAL• Agreements get renegotiated - check regularly.

• Make purchases in LUPIN - invoice!

• Tur & Retur reimburses twice monthly.

• Receipts below SEK 100 are not considered for reimbur-

sement, collect several receipts to reach a higher total.

• Ask katarina.danielson@med.lu.se or lisette.eklund@

med.lu.se when you have questions.

AGREEMENT DATABASEhttps://tendsign.com/go.aspx?ID=DT31kZMJ4t70O0Vgoxp6gL1sppevBTufAA%3d%3d

ANTIBODIES & CHEMICALS• Becton Dickinson AB

• Nordic Biosite AB

• Fisher Scientific GTF Aktiebolag

• Sigma-Aldrich Sweden AB

BREAKFASTBreakfast has to be simple and can only be served once

a week. Everything on top of bread, butter, cheese and

marmalade has to be paid for privately. If breakfast is served

as part of a meeting where there is an invitation and a

programme, more generous rules apply. Provide invitation,

programme and participant list when you ask for reimburse-

ment.

COMPUTERSThere are several contracts. Consult contract number 1 first,

and don’t move on to contract number 2 unless you are

unsatisfied with number 1. henrik.nottorp@eken.lu.se nego-

tiates for LU. He can answer questions.

PC LAPTOPS: 1) Dell AB - Dell Latitude

2) Dustin AB - Lenovo Thinkpad

3) Atea Sverige AB - HP Probook

STATIONARY PC:s:1) Dell AB - Dell OptiPlex 7010 pr 790

2) Atea Sverige AB - HP Compaq 6200

3) Dustin AB Lenovo Thinkcentre or HP COmpaq 6200

APPLE COMPUTERS:1) Atea Sverige AB - MacBook Pro 13”

2) Advania AB MacBook Pro 13”

3) Dustin AB MacBook Pro 13”

MacSupport: Support. Hardware only if you buy support.

iPADS ETC:1) Atea Sverige AB - iPad, HP Slate, Samsung Galaxy tab

2) Dustin AB - iPad, Dell ST, Samsung Galaxy tab

PHONES• LDC

All phones are bought at LDC; stationary and mobile.

REPRESENTATION -INTERNALA majority of LU employees. Max SEK 450 per person (VAT

excluded). Christmas lunch may be reimbursed with up to

SEK 650 (VAT excluded). Don’t tip more than 5% of the total

check. Hard liquor is never reimbursed. Provide invitation,

programme and participant list. If spouses are to attend,

please ask the management group’s permission ahead of

time.

REPRESENTATION -EXTERNALA majority of non-LU employees. Max SEK 650 per person

(VAT excluded). Hard liquor is never reimbursed. Don’t tip

more than 5% of the total check. Provide invitation, pro-

gramme and participant list.

TRAVEL TICKETS• Via Egencia

• Kilroy (students)

You must buy your trip through these agencies. If you find

something cheaper, inform them. They have to match the

price.

PURCHASING RULESFOR CLEVER DUMMIES. UPDATED 12-10-19

NEWSLETTER FOR THE DEPARTMENT OF EXPERIMENTAL MEDICAL SCIENCE

8 NEWSLETTER FOR THE DEPARTMENT OF EXPERIMENTAL MEDICAL SCIENCE

NOVEL DISEASE-SPECIFIC PROMOTERS FOR USE IN GENE THERAPY FOR PARKINSON’S DISEASE. Wetter-

gren EE, Gussing F, Quintino L, Lundberg C. Neurosci Lett.

2012 Oct 11. pii: S0304-3940(12)01321-3. doi: 10.1016/j.

neulet.2012.09.059. [Epub ahead of print] PMID: 23063686

DESTABILIZING DOMAINS MEDIATE REVERSIBLE TRANSGENE EXPRESSION IN THE BRAIN. Tai K, Quin-

tino L, Isaksson C, Gussing F, Lundberg C. PLoS One.

2012;7(9):e46269. doi: 10.1371/journal.pone.0046269. Epub

2012 Sep 28. PMID: 23029456

DEVELOPMENT OF NMR SPECTROSCOPIC METHODS FOR DYNAMIC DETECTION OF ACETYLCHOLINE SYN-THESIS BY CHOLINE ACETYLTRANSFERASE IN HIPPO-CAMPAL TISSUE. Hall H, Cuellar-Baena S, Denisov V, Kirik

D. J Neurochem. 2012 Sep 24. doi: 10.1111/jnc.12025. [Epub

ahead of print] PMID: 23004566

IDURONIC ACID IN CHONDROITIN/DERMATAN SUL-FATE: BIOSYNTHESIS AND BIOLOGICAL FUNCTION.Malmström A, Bartolini B, Thelin MA, Pacheco B, Maccarana

M. J Histochem Cytochem. 2012 Oct 4. [Epub ahead of print]

PMID: 22899863

DUAL R3R5 TROPISM CHARACTERIZES CEREBROSPI-NAL FLUID HIV-1 ISOLATES FROM INDIVIDUALS WITH HIGH CEREBROSPINAL FLUID VIRAL LOAD. Karlsson U,

Antonsson L, Ljungberg B, Medstrand P, Esbjörnsson J, Jans-

son M, Gisslen M. AIDS. 2012 Sep 10;26(14):1739-44. PMID:

22695299

DYSREGULATED DOPAMINE STORAGE INCREASES THE VULNERABILITY TO Α-SYNUCLEIN IN NIGRAL NEURONS.Ulusoy A, Björklund T, Buck K, Kirik D.

Neurobiol Dis. 2012 Sep;47(3):367-77. Epub 2012 May 31.

PMID: 22659302

KEY FACTORS DETERMINING THE EFFICACY OF GENE THERAPY FOR CONTINUOUS DOPA DELIVERY IN THE PARKINSONIAN BRAIN. Cederfjäll E, Sahin G, Kirik D. Neu-

robiol Dis. 2012 Nov;48(2):222-7. Epub 2011 Oct 25. PMID:

22048069

Publications with affiliation Dept of Experimental Medical Science

Gene therapy is a promising therapeutic tool for Parkinson’s

disease (PD). A vector system that is safe, specific and has an

appropriate transgene expression level is needed to make

gene therapy as beneficial as possible. The promoter plays

an important role in these vector characteristics, but there is

a lack of evaluated cell specific promoters that are relevant

for PD.

In this study, we have chosen PD relevant promoter candida-

tes for gene therapy vectors based on either previous studies

(hypothesis driven approach); Drd1a, Drd2 and pDyn, or from

a microarray study on parkinsonian patients (unbiased ap-

proach); ACE, DNAJC3, GALNS, MAP1a and RNF25. These

promoters have been evaluated in rat striatum to determine

their suitability for use in cell specific vectors.

The promoters had a neuronal specificity of 91-100%. The

efficiency was variable, but RNF25, DNAJC3 and MAP1a were

comparable to widely used ubiquitous promoters. MAP1a

was also affected by dopamine depletion. The results show

that these approaches can be used to find PD relevant pro-

moters with high specificity and efficiency.

Erika Elgstrand Wettergren

”Novel disease-specific promoters for use in gene therapy for Parkinson’s disease...

... explained:

9NEWSLETTER FOR THE DEPARTMENT OF EXPERIMENTAL MEDICAL SCIENCE

Organizing BMA-dagen2013 IT’S THEIR 10 YEAR ANNIVERSARY

BMA-dagen took place yesterday at the Sparta Konferens Hotel.

With such a skilled organizing committee, they are well prepared

for their jubilee. The group happily welcomes new members.

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