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Annual Report 2007

Annual Report 2007 - MFPL · Annual Report 2007 Contact | Max F. Perutz Laboratories Dr. Bohr-Gasse 9 ... Löffelhardt Wolfgang Meskiene Irute Moll Isabella …

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Annual Report 2007

Contact | Max F. Perutz LaboratoriesDr. Bohr-Gasse 9 | 1030 Vienna | AustriaPhone | [email protected] | www.mfpl.ac.at

MFPL are a joint venture of:

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enRü

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Alphabetical Group Leader Index

Editor | Lisa Cichocki

Design | Grafikatelier Heuberger | Vienna

Photography | Lisa Cichocki | Arnd Oetting – Porträt Seite 31 | Group Leader Archive

Printing | Kärntner Druckerei | Klagenfurt

Dr. Lisa Cichocki | Communications

Max F. Perutz Laboratories | Dr. Bohr -Gasse 9 | A -1030 Wien

T: +43 -1-4277-24014 | F: +43-1-4277-9240

E: [email protected] | W: http://mfpl.ac.at Lisa Cichocki

Imprint

Ammerer Gustav

Baccarini Manuela

Bachmair Andreas

Barta Andrea

Blaas Dieter

Bläsi Udo

Brocard Cécile

Charpentier Emmanuelle

Decker Thomas

Djinovic Carugo Kristina

Dong Gang

Dorner Silke

Foisner Roland

Gregan Juraj

Hartig Andreas

Heberle-Bors Erwin

Hermann Marcela

Hermisson Joachim

Hirt Heribert

Hofbauer Reinhold

Ivessa N.-Erwin

Jantsch Michael

Jantsch-Plunger Verena

Klein Franz

Koller Franz

Konrat Robert

Kovarik Pavel

Köhler Gottfried

Kragler Friedrich

Kuchler Karl

Loidl Josef

Lorkovic J. Zdravko

Löffelhardt Wolfgang

Meskiene Irute

Moll Isabella

Müllner Ernst

Nimpf Johannes

Ogris Egon

Pichler Andrea

Pittner Fritz

Poppenberger Brigitte

Prohaska Rainer

Propst Friedrich

Raible Florian

Rotheneder Johann

Schlögelhofer Peter

Schneider Wolfgang

Schroeder Renée

Schüller Christoph

Schweyen Rudolf

Seipelt Joachim

Seiser Christian

Sieberer Tobias

Skern Tim

Teige Markus

Tessmar Kristin

Touraev Alisher

Von Haeseler Arndt

Waigmann Elisabeth

Warren Graham

Wawra Edgar

Weitzer Georg

Wiche Gerhard

Witte Angela

Wohlrab Franz

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Content

Foreword – Message from the Rectors

Report of the Directors

History

Facts

Undergraduate Students at MFPL

PhD and Postdocs at MFPL

Research Programme Infection Biology

Research Programme RNA Biology

Research Programme Cell Signaling

Research Programme Structural and Computational Biology

Research Programme Chromosome Biology

Research Programme Membranes and the Cytoskeleton

Junior Group Leaders

Service & Support

Social Life

Research Funding

Where to find MFPL

Imprint

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In 2005 the University of Vienna and the Me-dical University of Vienna decided to createthe Max F. Perutz Laboratories as a joint initia-tive. Building on the existing strength of morethan 50 research groups in the field of Mole-cular Biology, the two universities have the in-tention to further develop the MFPL as an inter-nationally visible environment for excellent re-search and training.

The progress that has been achieved so far isimpressive. As rectors of the two universities wewant to encourage the MFPL to continue crea-ting new opportunities for young researchersand increase the synergistic effects made pos-sible by pooling infrastructure and know-how.The Scientific Advisory Board of the MFPL willprovide invaluable input for this.

In many ways we would like to see the MFPLacting as a ”test-bed“ within the universities fortrying out new approaches. The MFPL GmbH

is one example, where we established a newstructure to build a strong and institutionalizedbridge between our two universities. Another ex-ample is the establishment of Junior Groups –we see the financial support we provide in theform of a substantial start-up package as astrong signal and an investment in exciting newresearch areas.

Both universities fully support the initiatives plan-ned for the near future: implementing the Vision2020 for the Campus Vienna Biocenter and theapplication for an Excellence Cluster. Anotherimportant activity in 2008 will be to forge clo-ser ties to clinical research groups and – last butnot least – continue the efforts to establish aCampus wide Graduate School. Together withmentoring and career development activitiesat all stages of the scientific career we regardthe establishment of structured training program-mes for PhD students as a crucial endeavour forthe near future.

Wolfgang SchützRector Medical University of Vienna

Georg WincklerRector University of Vienna

WolfgangSchütz

GeorgWinckler

2

Foreword

Message from the Rectors

01-07_Einstieg 27.05.2008 13:13 Uhr Seite 2

The appointment of Graham as Scientific Direc-tor (1.1.2007) marked the completion of yearsof preparatory work and sent a strong signal forthe start of a new enterprise. The creation of theMax F. Perutz Laboratories was the result ofdedicated work by many individuals whom wewish to thank for their persistence and efforts inthe face of many hurdles.

A number of new iniatives were started in 2007:The Research Programmes were assembled ina bottom-up fashion to provide more focus anda stronger identity – particularly important formentoring everyone from students to group lead-ers. A monthly MFPL seminar series was establis-hed and all group leaders are invited to a wee-kly ”chalk talk“ given by one of the faculty pro-viding an informal forum for new ideas and pro-jects amongst the MFPL faculty.

The first call for Junior Group Leader positionswas started in May and proved to be a hugesuccess. From more than 100 applications wewere able to select three outstanding newgroup leaders: Gang Dong (Yale), Kristin Tess-mar and Florian Raible (both from EMBL) will setup their own research groups from 2008 on-wards.

In an effort to establish a joint Graduate Schoolwe used the experience gathered in the long-running ”Wissenschaftskolleg“ to include allPhD students in quality controlled selection andsupervision. We also invited our PhD students

and PostDocs to nominate representatives toprovide more involvement in MFPL issues.

To enhance the flow of information we introdu-ced regular meetings of the administrative staff aswell as floor meetings and a faculty committee(with representatives from all the research pro-grammes). Vice-deans were also appointed:Manuela Baccarini for the University of Viennaand Roland Foisner for the Medical UniversityVienna.

We continued the tradition of Happy Hours andventured into new activities such the Dragonbo-at Cup and the Business Run where a great mixof MFPL sports fans gave of their best.

2007 also saw the beginning of our perfor-mance oriented budget allocation and the startof space reallocations. The new budget alloca-tion systems provide transparency and financi-al benefits to those research groups who arestrong in acquiring third party funding and pu-blish in prestigious journals.

Last but not least our research groups continu-ed to acquire substantial third party funds. Themost prominent achievements were the appro-val of a second WWTF chair in biomathema-tics (Joachim Hermisson), a new Christian Dopp-ler Laboratory with the focus on ”Infection bio-logy“ (Karl Kuchler) and a new Doktoratskollegon ”RNA biology“ (Speaker: Andrea Barta). ... and 2007 was just the beginning!

GrahamWarrenScientific

Director MFPL

HaraldHochreiter

AdministrativeDirector MFPL

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Graham WarrenScientific Director

Harald HochreiterAdministrative Director

Report of the Directors

2007 was the year when it really began ...

01-07_Einstieg 27.05.2008 13:13 Uhr Seite 3

History

1992/1993 University departments move to the VBC (Molecular Biology, Biochemistry,

Medical Biochemistry, and Genetics)

Three new chairs established (Molecular Genetics, Molecular Cell Biology,

and Microbiology)

1994 Start of the international VBC PhD programme

1996 Max Perutz Library established

1998 Spin-Off company Intercell founded

1999 New chair for Immunobiology established

2001 Dept. for Structural Biology moves to the VBC

New Chair for Structural Biology / NMR established

New Chair for X-Ray Crystallography established

2004 Medical University of Vienna established

2005 Dept. for Chromosome Biology moves to the VBC

Max F. Perutz Laboratories GmbH established

Administrative Director appointed

Scientific Advisory Board established

2007 Scientific Director appointed

Max F. Perutz – ”In science, truth always wins“

To honour an extraordinary teacher and scientist,the MFPL was named after Max Ferdinand Perutz,the 1962 Nobel laureate in Chemistry (togetherwith John C. Kendrew) for studies of the structu-res of globular proteins. Born in 1914 in Vienna, he came from a family oftextile manufacturers who had made their fortunein the 19th century by the introduction of medicalspinning and weaving. He was sent to school atthe Theresianum where a good schoolmasterawakened his interest in chemistry. In 1932 he en-tered the University of Vienna, but owing to thepoor prospects for a scientific career he decidedin 1936 to become a research student at the Ca-vendish Laboratory in Cambridge. After Hitler´sinvasion of Austria, the family business was expro-

priated, his pa-rents became re-fugees and hisnatural choicewas to continuehis career in Cam-bridge.In addition to his studies on the structure of hae-moglobin, Max F. Perutz was highly instrumentalin founding the new research field of MolecularBiology as well as the Laboratory of MolecularBiology (LMB) in Cambridge, UK. He was alsoinvolved in establishing the European MolecularBiology Organization (EMBO) in Heidelberg,Germany.Max F. Perutz died in February 2002.

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History

01-07_Einstieg 27.05.2008 13:13 Uhr Seite 4

The Max F. Perutz LaboratoriesThe Max F. Perutz Laboratories (MFPL) are a jointventure of the University of Vienna and theMedical University of Vienna and are located atthe Campus Vienna Biocenter. Established in thespring of 2005 the MFPL comprises the expertiseof more than 60 research groups in MolecularCell Biology. They represent a new and innovativeapproach to strengthen research and training atboth Universities. This visionary inter-university cooperation provides asuperb environment for excellent research and edu-cation and is a platform for ventures across traditio-nal boundaries. New research groups are current-ly being established, existing synergies improvedand new collaborations actively promoted.

FundingThe Max F. Perutz Laboratories are jointly funded bythe University of Vienna and the Medical Universi-ty of Vienna. The two universities fund personnel, buil-dings and scientific infrastructure.Most of the personnel are funded by grants. Re-search groups at the MFPL have always had astrong track record in acquiring external funding: in2007 the total volume of third party funding wasEUR 9,8 Mio.The main external sources of funding in 2007 we-re the FWF (EUR 4,6 Mio.), the WWTF(EUR 1,5 Mio.) and the EU (EUR 1,3 Mio.); com-pany projects (EUR 0,8 Mio.) and other fundingorganisations (EUR 1,6 Mio.) amounted to onequarter of the financial income.

Scientific Director: Graham Warren, FRSAdministrative Director: Harald HochreiterScientific Advisory Board:Jean Beggs, University of Edinburgh

David Livingston, Dana-Farber Cancer Institute, Harvard Medical School

Kim Nasmyth, University of Oxford Nadia Rosenthal, EMBL Monterotondo Kai Simons, Max Planck Institute CBG Dresden

Overview – MFPL in 2007 • Had more than 450 people• From more than 25 nations• Had 60 research groups• In 6 research programmes• 70% of personnel funded by grants• Published 255 publications• Had 700 Undergraduate students• More than 120 PhD students• More than EUR 9,8 Mio grant money

MFPL – strength in diversityEmbedded in the Campus Vienna Biocenter, a uni-que concentration of high-level research institutes,MFPL provides a perfect environment for outstandingresearch. The MFPL covers research groups with abroad thematic profile - the majority work on basicresearch topics but a significant number are also ac-tive in more applied fields of biology. To maintainresearch at internationally competitive levels theMFPL is organized into six thematic Research Pro-grammes. These are:

• Infection Biology• RNA Biology• Cell Signaling• Computational and Structural Biology• Chromosome Biology• Membranes and the Cytoskeleton

FWF 4.622.357

WWTF 1.487.461

EU 1.282.831

Companies 829.867

Ministries 755.164

Trusts 349.525

Miscellaneous 162.970

ÖAW 143.400

FFG 93.390

Interreg 78.341

DFG 46.400

OeNB 15.032

Hochschuljubiläumsstiftung/MA8 11.748

Total 9.878.486

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Facts

Other17%

Companies8%

EU 13%

WWTF15%

FWF 47%

Third party funds 2007

01-07_Einstieg 27.05.2008 13:13 Uhr Seite 5

MPFL scientists strive not only to achieve scientific excellence but are also responsible for educating and

training the next generation of top scientists.

MPFL scientists give lectures as part of the undergraduate courses for life science and medical students,

supervise diploma students and support postgraduate scientists taking their first steps in their scientific ca-

reers. Degrees can be obtained from the University of Vienna and the Medical University of Vienna.

Studies at MFPL:

• Bachelor of Biology

• Masters of Molecular Sciences

• PhD programmes

Responsibilities of the StudyServiceCenter (SSC)

The staff members of the SSC are available for all questions of the ongoing Study Program for students

and the university lecturers. For students it has become a central place at MFPL where they can get any

information and help on administrative requirements of the provided studies. We support parts of the Ba-

chelor of Biology, Masters of Molecular Sciences, and the ongoing PhD Programmes.

The main agenda are:

• Information about the running Study Program at the Center of Molecular Biology, MFPL

• Help on administrative procedures regarding the studies

• Administration of teaching affairs ranging from organization of lectures up to awarding degrees

Main contact:

Student Secretariat: Dr.Bohr -Gasse 9, 6th Floor

Opening times: Tue, Wed: 9.00 – 12.00 and Thu: 9.00 – 12.00 + 13.00 -14.00

Opening times during semester breaks: Tue to Thu: 9.00 – 12.00

Renate Fauland

Phone: +43-1-4277- 50115

Dr. Barbara Hamilton

Head of Molecular Biology Study Programme

Phone: +43-1-4277- 52814

Dr. Angela Witte

Deputy of Molecular Biology Study Programme

Phone: +43-4277-54643

Current Doctoral Programmes at MFPL

RNA Biology

Coordinator: Andrea Barta

http://www.projects.mfpl.ac.at/dk-rna-biology/

Functional Organization of the Nucleus

Coordinator: Pavel Kovarik

http://www.univie.ac.at/ik-cellnucleus/

”Molecular mechanisms in cell biology“ PhD Programme at the Medical University

Coordinator: Johannes Nimpf

http://www.meduniwien.ac.at/index.php?id=431&language=1&content_id=studium_u_lehre/stu-

dien/co_phd_theme2_1.php

VBC PhD Programme

Joint PhD Programme of all institutes at the Vienna Biocenter Campus

http://www.univie.ac.at/vbc/PhD/

6

Undergraduate Students at MFPL

RenateFauland

BarbaraHamilton

Angela Witte

01-07_Einstieg 27.05.2008 13:13 Uhr Seite 6

7

PhDs and Postdocs at MFPL

Théodora Niault

PhDRepresentatives

PostdocRepresentatives

Florian Kern

LukasRajkowitsch

ChristelleBourgeois

The recently established MFPL PostDoc associati-on aims to support this very heterogeneous group ofresearchers to get the most out of their PostDoc expe-rience. Its main focus is on• hard and soft skills development• promotion of communication and exchange within

the PostDoc community• networking in generalA post-doctoral training at MFPL can be the perfect step-ping stone for an academic career, but MFPL PostDocsalso have a variety of other career options (e.g.research and development in the biotech & pharmacyindustries, publishing, marketing & sales, patenting,governmental agencies). In addition to supporting aca-demic developments we seek to make these non-univer-sity careers more accessible.The PostDoc association greatly benefits from continu-ous support of the MFPL directors and faculty members,and regularly partners with the MFPL PhD students foragendas of mutual interest.

Since January 2008• more than 60 PostDocs have signed up• an Intranet PostDoc website with a discussion forum

was launched• German courses are held for incoming PostDocs and

PhD students• current topics are discussed at regular meetings• the creation of a PostDoc and PhD ”study area“ has

been initiatedFuture projects include• career workshops and networking events• scientific workshops and hands-on trainings• soft skills workshops (presentation techniques,

scientific English etc)• MFPL PostDoc & PhD retreatFor more information, or if you will be starting soon asPostDoc at the MFPL, please do not hesitate to contactthe representatives.

[email protected]@univie.ac.at

Internationality – We, the MFPL PhD students, comefrom an exceptionally diverse scientific and cultural back-ground, combining our forces to move the scientific worldforward.Community – As an active community we are able tomake our voice heard at the research program, faculty anddean meetings. Therefore we are part of and contributeto the idea of MFPL, e.g. together with the MFPL Post-Docswe organized a German course for our international fel-lows and established an online forum in our intranet to fa-cilitate communication. Excellence – We seek to bring into being innovative andhigh-quality science. MFPL PhD students are selectedthrough a competitive selection procedure. Throughout ourPhD studies, as students at MFPL we are followed and sup-ported by a PhD thesis committee, complementing thestandard one-mentor-one-student-system. Outstanding

awards and exceptional publications in high impact fac-tor journals are the read-out of our excellence.Networking – Initiating collaboration, tightening thelinks between and beyond the institutes on the Vienna BioCenter campus and contributing to the joint campus-wi-de organization of international symposia are just a fewof our networking activities. Career – Obtaining a PhD degree at MFPL grants a su-perb stepping-stone to career success in academia as wellas in industry.Vision – Our aim is to support and strengthen the MFPLPhD community, increasing the interactions in-betweenand beyond the students at MFPL to create an internatio-nally and scientifically recognized community.For more inforamtion please contact:[email protected]@univie.ac.at

Armin DjameiVBC PhD Award

Stefan AmeresVBC PhD Award

Nana NaetarL’Oreal Award

01-07_Einstieg 27.05.2008 13:13 Uhr Seite 7

Signal transduction in cells infected with Listeriamonocytogenes. Cytoplasmic recognition of the

bacteria stimulates type I interferon synthesisthrough transcription factor IRF3. Secreted type

I interferons subsequently induce a distinct setof antimicrobial genes through STAT transcripti-

on factors.

Research Programme Infection Biology

In recent years, newly emerging infectious diseases, antibiotic-resistant super-bacteria and fears of viral pandemics have increased the awareness that thebattle with microbes is far from over. Research is thus needed to determinehow host organisms try to fend off microbes and the strategies by whichpathogens circumvent these defensive efforts.

The Host-Pathogen Biology cluster comprises groups studying fungal, bacterialand viral pathogens with respect to the molecules and molecular pathwaysinvolved in pathogenic processes leading to acute, chronic or lethal infection.Furthermore, the ways in which different microbes are recognized by the host

When cells encounter microbes they respond with an innateantimicrobial immune response. One of the hallmarks of thisresponse is the deployment of a pathway targeting transcrip-tion factor IRF3, and the IRF3-dependent transcription of typeI interferon (IFN-I) genes. IFN-I subsequently stimulate a Jak(tyrosine kinase)-Stat (transcription factor) signaling pathway.We investigate the importance of this scenario upon infecti-on with the intracellular bacterial pathogen Listeria monocy-togenes. We study how L. monocytogenes causes IRF3 acti-vation and how IRFs, Stats and other transcription factors acti-vated upon bacterial infection cooperate in gene activation.Studying the influence of IFN-I on innate immunity to L. monocytogenes we observed that IFN-Ienhance the pathological changes accompanying Listera infection, thus sensitizing cells and ani-mals to lethal [email protected]

Interferons, Jaks and Stats in innate immunity

ThomasDecker

8

Selected PublicationsRamsauer K. et al. 2007. Distinct modesof action applied by transcription fac-tors STAT1 and IRF1 to initiate tran-scription of the IFN-gamma-induciblegbp2 gene. Proc. Natl. Acad. Sci. 104:2849-2854.

Schindler C. et al. 2007. JAK-STATSignaling: from Interferons to Cyto-kines. J. Biol. Chem. 282: 2059-2063.Team

Matthias FarlikRenate KastnerElisabeth KernbauerAndreas PilzBirgit RappBenjamin ReuttererDidier SoulatUschi StixSilvia StockingerFatima Touraeva Sandra Westermayer

08-13_Kapitel1 27.05.2008 13:38 Uhr Seite 8

The structure of the Foot-and-Mouth leader proteinase, a keymodulator of protein synthesis inthe infected cell.

Speaker Infection BiologyThomas Decker

Deputy Speaker Timothy Skern

Most viruses interfere with or modulate host systems to ensuresuccessful replication. My group has been looking at the inter-actions between proteinases of the common cold virus, foot-and-mouth disease virus and coxsackievirus with a cellular pro-tein involved in protein synthesis. We have determined themolecular structures of some of these proteins and investigatedthe sites at which they interact. In collaboration with ChristianMandl (Medical University Vienna), we have also started toexamine how the tick-borne encephalitis virus proteins aresynthesised in an infected cell and to use the inherent error rate

of this virus as a tool to randomly mutagenise specific viral proteins. These approaches lay thegroundwork for the identification and development of novel anti-viral agents. [email protected]

Interactions between viruses and cells

immune system and how recognition sparks an antimicrobial response areunder intense investigation. Strategies include microbial genetics and “patho-gene“ identification strategies, proteomic, biochemical and structural studies ofinteractions between microbial and host cell proteins, as well as analysis oftransgenic or gene-deficient mice for alterations in their antimicrobial responses.

Taken together, these studies aim at identifying hitherto unknown determinantsof pathology-prone encounters of microbes with their mammalian host organ-isms, as well as furthering knowledge about the contribution of known mole-cules to pathogenicity and/or a lack of efficient host defense.

9

Tim Skern

TeamMartina Kurz

David Neubauer Carla Sousa

Jutta Steinberger Sabrina Schrauf

Selected Publications Cencic R. et al. 2007. Investigating thesubstrate specificity and oligomerisa-tion of the leader proteinase of foot-and-mouth disease virus using NMR.J. Mol. Biol. 373:1071-1087.

Deszcz L. et al. 2006. An anti-viralpeptide inhibitor active against picor-naviral proteinases but not cellularcaspases. J. Virol. 80:9619-9627.

08-13_Kapitel1 27.05.2008 13:38 Uhr Seite 9

Phagocytosis of Candida albicans by mouse macrophages.Filamentation of the fungal pathogen inside host cells leads to

the killing of immune cells through the physical force generatedby the elongating fungal filaments.

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Molecular mechanisms driving virulence of human fungal pathogens

Karl Kuchler

My group is interested to understand the molecularmechanisms of fungal pathogenicity. On the pathogenside, we pursue reverse genetics approaches to identifypathogenicity and drug resistance genes, the roles ofepigenetic modifications in morphogenetic switching,and we develop antibody-based approaches to com-bat fungal disease. Further, we also dissect the structureand function of membrane ABC transporters conferringmultidrug resistance. On the host side, we are studyingprotective response in primary innate immune cellsfacing pathogens, including protective and inflammato-ry type I and II interferon, as well as comprehensive cytokine responses to fungal pathogens. Finally,we pursue systems biology approaches by exploiting quantitative biology paired with mathematicalmodeling to answer how stress signalling pathways impact growth control and proliferation in [email protected]

Grant Support: Our work is supported by grants from 6th and 7th frame-work programmes of the European Commission, the Christian DopplerResearch Society, the Austrian Science Foundation FWF, the transnationalERA-Net Pathogenomics scheme, the SysMO programme through theAustrain GenAU, the Austrian Academic Exchange Service and by theAustrian FFG.

TeamChristelle BourgeoisIngrid FrohnerWalter GlaserChrista GregoriDenes HniszRegina KlausCornelia KleinNathalie LandstetterOlivia MajerTobias SchwarzmüllerKristina SliwozkyMichael TschernerMartin ValachovicFlorian Zwolanek

Selected PublicationsGregori C. et al. 2007. The high osmolarityglycerol (HOG) response in the humanpathogen Candida glabrata lacks a signa-ling branch operating in baker’s yeast.Eukarotic Cell 6:1635-1645.

Mamnun Y.M. et al. 2007. Membraneactivecompounds activate the transcription factorsPdr1 and Pdr3 connecting pleiotropic drugresistance and membrane lipid homeostasisin Saccharomyces cerevisiae. Mol. Biol. Cell18:4932-4944.

08-13_Kapitel1 27.05.2008 13:38 Uhr Seite 10

Regulatory networks involved in the control ofvirulence factor expression in Streptococcuspyogenes. Virulence factors consist mainly ofsurface-exposed and secreted proteins. Theirexpression is regulated by two-componentregulatory systems, stand alone regulators,chaperones, proteases and small regulatoryRNAs. These regulatory components are impli-cated in a complex network, which implicatessensing and responding to changing environ-mental conditions encountered within the hostduring an ongoing infection process.

Receptor attachment sites in minorand major group HRVs. Twenty-fourcopies of a VLDLR fragment (modu-les 2 and 3, i.e. V23) bind to theminor group virus HRV2 at the star-shaped dome close to the five-foldaxis of icosahedral symmetry where-as 60 ICAM-1 molecules bind intothe canyon of the major group virusHRV16. Note that each V23 occu-pies 2 binding sites on the virus withone site remaining unoccupied (notseen because of the averaging).

11

Our group is interested in the early steps in infection of thehost cell by human rhinoviruses, the main causative agent ofthe common cold. We study the specific recognition of viralserotypes by cellular receptors and analyse the interactingsurfaces on the atomic level. Other topics are the internali-zation pathway and the mechanism of release of the viralgenome into the cytosol. Finally, we want to unravel thebasis of the evolution of two viral groups using differentreceptors albeit being closely related. [email protected]

Early steps in common cold infection

Dieter Blaas

TeamIrene Gösler

Abdul Ghafoor Khan Tünde Konecsni

Angela Maria Pickl-Herk

Institute for Analytical Chemistry:

Gerhard Bilek

Selected PublicationsKhan A.G. et al. 2007. Human rhinovirustype 54 infection via heparan sulfate isless efficient and strictly dependent onlow endosomal pH. J. Virol. 81:4625-4632.

Wruss J. et al. 2007. Attachment of VLDLreceptors to an icosahedral virus alongthe 5-fold symmetry axis: multiple bin-ding modes evidenced by fluorescencecorrelation spectroscopy. Biochemistry46:6331-6339.

HRV2 / VLDLR (V23)

HRV16 / ICAM-1(domain 1 and 2)

During an ongoing disease process, pathogens are heavilyexposed to different specific and non-specific host defencemechanisms, amongst others growth-limiting conditions andstress factors at the site of infection. To thrive under these hosti-le conditions, pathogenic bacteria have developed well-direc-ted strategies leading to a coordinated expression of virulencefactors in response to host-induced environmental changes. Inthis regard, our group is interested in the understanding of themolecular mechanisms governing the interaction of gram-positi-ve pathogens with their hosts, employing the human pathogen

Streptococcus pyogenes (Group A streptococcus, GAS) as a model organism. In particular, small regu-latory RNA molecules and regulated proteolysis play key roles in gram-positive bacterial pathogenesisand constitute the current research focus of our lab. [email protected]

Molecular mechanisms governing gram-positive bacterial pathogenesis

EmmanuelleCharpentier

TeamFanny Beneyt

Stephanie Füreder Karine Gonzales

Zaid Ahmed Pirzada Silvia Spiess

Selected PublicationMangold M. et al. 2004. Synthesis ofgroup A streptococcal virulence factorsis controlled by a regulatory RNA mole-cule. Mol. Microbiol. 53:1515-1527.

Garnier F. et al. 2007. Insertion sequen-ce1515 in the ply gene of a type 1 clini-cal isolate of Streptococcus pneumoniaeabolishes pneumolysin expression.J. Clin. Microbiol. 45:2296-2297.

12 HRV-A Types bind LDLR, 61 bind ICAM-1 for Cell Entry

08-13_Kapitel1 27.05.2008 13:38 Uhr Seite 11

Interferon-inducedtranslocation of thetranscription factorStat1 into the cell

nucleus.A: untreated cells;

B: cells treated for 10 min with inter-

feron-gamma

12

The precise regulation of gene expression in response toextracellular stimuli plays a key role in life and biologicaldiversity. How cells respond to multiple external cues andintegrate them into appropriate changes in expression is achallenging question. We are addressing this issue by study-ing responses of the innate immune system to inflammatorystimuli. Stimulation of macrophages by bacterial productsand interferons launches a full-blown inflammation followedby negative feedback programs. Many immune disordersare caused by still poorly understood failures in activation or attenuation of the innate responses. Byexamining gene expression, upstream signaling events as well as downstream changes in chroma-tin structure we aim to provide mechanistic explanations for the principles of normal and aberrantimmune responses. [email protected]

Signaling and gene expression in inflammation

Pavel Kovarik

TeamJoanna Bancerek Nina Gratz Franz Kratochvill Christian Machacek Iwona Sadzak

Selected PublicationsKovarik P. et al. 2007. Molecular me-chanisms of the anti-inflammatoryfunctions of interferons. Immunobiology212:895-901.

Sauer I. et al. 2006. Interferons limitinflammatory responses by induction oftristetraprolin. Blood 107:4790-4797.

We are interested in the molecular mechanisms of interacti-ons between viruses and host cells. Even a small and simplevirus such as the human rhinovirus can in a short timeframesubvert a eucaryotic cell into a virus producing machine.Cells try to defend themselves against intruders, but at thesame time viruses have evolved complex strategies to avoidcellular defence reactions. Analysis of this interplay betweenhost and virus can provide new insights into both viral andcellular functions. Our current research topics include mecha-nisms of antiviral compounds, characterisation of virus-indu-ced apoptotic processes and developments for a possibleuse of specific viruses in cancer [email protected]

Virus-host interactions

JoachimSeipelt

TeamAndreas Alber Elisabeth Gaudernak Karin Habegger Barbara Holzer Andrea Triendl

Selected PublicationsLanke K. et al. PDTC inhibits picorna-virus polyprotein processing andRNA replication by transporting zincions into cells. J. Gen Virol. 88:1206-1217.

Krenn B. et al. 2005. The inhibition ofpolyprotein processing and RNAreplication of Human Rhinovirus byPDTC depends on metal ions. J. Virol.79:13892-13899.

HeLa cells (left) after infection with human rhinovirus (right).Actin is shown in red, cytokeratin 8 in green.

08-13_Kapitel1 27.05.2008 13:38 Uhr Seite 12

Tobacco mosaic virus movement protein, expressed as GFPfusion protein in epidermal cell of tobacco. Cell to cellmovement is indicated by arrows.

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We use viruses, pathogens that depend on cellular mecha-nisms to complete their own life cycle, to gain insight into cel-lular functions. The major research emphasis is placed onmechanisms of macromolecular transport, exemplified bytwo types of transport processes. 1) The intra- and intercellular transport of plant viral geno-mes, frequently RNA, between plant cells. This transport pro-

cess takes place through plasmodesmata and is mediated by specialized plant viral proteins, themovement proteins. A special focus is placed on host and environmental factors that modulate theinfection process.2) Transport of HIV proteins such as Tat and Rev from the cytoplasm to the nucleus. This transport

process is essential for completion of the HIV life cycle. [email protected]

Viral systems as models for transport processes

ElisabethWaigmann

TeamDaniela Fichtenbauer

Pia RuggenthalerGrazia Kocian

Selected PublicationCurin M. et al. 2007. MPB2C, a micro-tubule-associated plant factor, isrequired for microtubular accumulati-on of tobacco mosaic virus movementprotein in plants. Plant Physiol. 143:801-811.

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Model for human RISC-mediated target recognition andcleavage. RISC-mediated target recognition is limited by theaccessibility of the target mRNA. RISC interacts non-specifi-

cally with single-stranded RNA promoting annealing ofsiRNA and target RNA. The initial specific RISC-target asso-

ciation is primarily mediated via the 5’-part of the siRNA,whereas annealing of the 3’-part is disfavoured. In case of a

high degree of complementarity and accessibility, targetcleavage occurs. Target release is rate limiting for multiple

rounds of cleavage.

Research Programme RNA Biology

RNA research is experiencing an unprecedented boom, owing to the disco-very of hundreds (if not thousands) of novel functional RNAs. Transcriptomeanalyses suggest that genomes are completely transcribed into RNAs,whose functions are still mostly unknown. The major roles played by RNAsin cells are connected with gene expression and its regulation, but recentroles include RNAs shaping chromatin structure and regulating epigeneticphenomena.

The RNA biology cluster aims to understand the mechanisms underlying theseprocesses by elucidating how RNA molecules interact with proteins rangingfrom ADARs, RNA chaperones and polymerases, to chromatin remodelingcomplexes, ribosomes, and spliceosomes. It will be important to understandhow RNAs sense intracellular levels of metabolites, temperature or other envi-

The past years have completely changed our perception ofRNA. RNA is now clearly perceived as the central moleculethat shapes our genomes. RNA is pivotal to the regulation ofmost essential processes in the cell. Because RNA has keptme enthusiastic for twenty years with my enthusiasm growingfrom year to year, I intend to continue studying RNA to beable to understand how RNAs can fulfil so many differenttasks. Our knowledge in RNA structure and function hasincreased to a point that more detailed and deeper problems can be addressed: How does RNAreach its native functional state? How do proteins contribute to RNA’s folding pathways? How doesRNA interact with itself and with other molecules? [email protected]

Regulatory RNAs and RNA Chaperones

RenéeSchroeder

TeamStefan Ameres Jennifer Boots Doris Chen Martina Dötsch Boris Fürtig Peter Hajdusits Christina LorenzKatarzyna Matylla Oliver Mayer Frederike von PelchrzymLukas Rajkowitsch Ursula SchöberlKatharina Semrad Marina Skern Sabine Stampfl Christina Waldsich Robert Paul Zimmermann

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Selected PublicationsAmeres S. L. et al. 2007. Molecular basisfor RISC mediated target recognitionand cleavage. Cell 130:101-112.

Rajkowitsch L., Schroeder R. 2007.Dissecting RNA Chaperone Activity.RNA 13:2053-2060.

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X-ray structure of the Hfq-hexamer from Pseudomonas aeruginosa.

Speaker RNA BiologyRenée Schroeder

Deputy Speaker Udo Bläsi

Regulation of gene expression in response to environmentalstimuli is a major theme in Molecular Microbiology. Ourmain interests focus on post-transcriptional control mecha-nisms exerted by the global regulator protein Hfq in con-junction with small regulatory RNAs (sRNAs) in Eubacteria,with emphasis on the human pathogen Pseudomonas aeru-ginosa. These studies revealed novel molecular modes ofsRNA function as well as Pseudomonas sRNAs contributingto pathogenicity. Another project aims at a better understanding of the pro-cess of translation initiation in the model crenarchaeon

Sulfolobus solfataricus. During these studies unpre-cedented function(s) of archaeal translation initia-tion factors were [email protected]

Post-transcriptional regulation in Bacteria and Archaea

ronmental signals that lead to a change in gene expression, and how theyexert regulatory functions in a number of biological processes. To reachthese goals will require an interdisciplinary approach utilizing genetics, bio-chemistry, imaging, bioinformatics and structural biology. Model organismsbeing used range from E. coli and pathogenic bacteria, to yeast, plants andmammals. The research cluster is strengthened by an SFB (RNA Fate andFunction) and by a Doctorate programme in RNA biology, which links theMFPL groups with research groups at the IMP, IMBA and CEMM and withgroups at the Medical University.

The ultimate goal is to determine how RNA activities influence genome struc-ture and gene expression, ultimately leading to the modulation of essentialbiological functions.

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Udo Bläsi

TeamLuisa Antunes

Hermann Haemmerle David Hasenöhrl

Masayuki Nakano Kristina Palavra

Armin Resch Alessandra Romeo

Theresa Sorger-Domenigg Roland Tschismarov

Branislav Vecerek

Selected PublicationsSonnleitner E. et al. 2006. Hfq-depen-dent alterations of the transcriptomeprofile and effects on quorum sensingin Pseudomonas aeruginosa. Mol. Mi-crobiol. 59:1542-1558.

Nikonov O. S. et al. 2007. New insightsinto the interaction of translationinitiation factor 2 from archaea withguanine nucleotides and initiatortRNA. J. Mol. Biol. 373:328-336.

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The alternative splicing factor, SR protein atRSp31regulates flowering time of Arabidopsis thaliana.

Ectopic overexpression of atRSp31 (ox) causeslate flowering (17 weeks) whereas plants which

do not express atRSp31 (mut) flower early (4weeks). Wild type plants flower in about 7 weeks

under the test conditions.

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My research interests center on how the structures of RNPcomplexes relate to their particular function. It is one of thekey questions to dissect the contributions of RNA and pro-teins to the various activities of the RNP particle. Our mainfocus to date concerns the spliceosome investigating mainlythe problem of splice site recognition and how the variabili-ty of this process influences gene expression and consequently organ development. A longstandinginterest has also been the contribution of the ribosomal RNA to ribosomal dynamics and peptidebond formation. Consequentially, our recent interest has been shifted towards other small non-con-ding RNP complexes and their influence on gene [email protected]

Contributions of RNA-protein complexes to regulation of gene expression

Andrea Barta

TeamOlga Bannikova Janett Göhring Aida Hajdarpasic Rugaia Idris Mariya Kalyna Branislav Kusenda Monika MaronovaClaudia Panuschka

Selected PublicationKalyna M. et al. 2006. Evolutionaryconservation and regulation of parti-cular alternative splicing events inplant SR protein protein. Nucleic AcidsRes. 344:4395-43405.

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Kasugamycin leads to the accumulation of protein defi-cient 61S ribosomes active in translation of leaderlessmRNA in vivo. A.) Ribosome profile analysis showing theformation of 61S ribosomes upon addition of kasuga-mycin in the presence of a plasmid encoded leaderlesscI-lacZ mRNA in vivo (red line). B.) Binding sites ofkasugamycin within the mRNA track of the 30S subunit(red arrow; Schluenzen et al., 2006).

ADARs bind double stranded RNAs and convert adenosi-nes to inosines by deamination. This mechanism is veryabundant in metazoa and has widespread impact on thecoding potential, processing, and structure of editedRNAs.

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RNA editing by adenosine deaminases that act on RNAs(ADARs) is a wide spread phenomenon in metazoa. ADARsconvert adenosines (A) to inosines (I) in double-stranded orstructured substrate RNAs. Since inosines have the base pai-ring potential of guanosines (G) this type of editing can leadto codon exchanges, alter splice sites, or influence the loca-lization and stability of an RNA. Thus ADARs lead to anincrease in transcritpome complexity.

Our work is focused on two main subjects: On the one hand the mechanisms by which ADAR-media-ted editing is regulated are investigated. On the other hand the impact of editing on coding andnon-coding substrates is being studied. [email protected]

RNA-editing and -processing

MichaelJantsch

TeamArmin Baghestanian

Drasko Boko Wojciech Garncarz

Dominik Muggenhumer Michael Müller

Nan Tian Dieter Pullirsch

Angelo Raggioli Sandy Schopoff

Aamira Tariq

Selected Publications Schoft V. K. et al. 2007. Regulation ofglutamate receptor B pre-mRNA spli-cing by RNA editing. Nucleic Acids Res.35:3723-3732.

Hallegger M. et al. 2006. RNA-apta-mers binding double-stranded RNA-binding domains. RNA 12:1993-2004.

Translation of the genetic code into proteins is performed bythe ribosome, a large ribonucleoprotein machine. We studythe effect(s) of antibiotics on ribosome assembly. Recently,we showed that in the presence of Kasugamycin in vivo pro-tein-deficient 61S ribosomes accumulate, which are active intranslation of a particular class of mRNAs lacking a 5’-UTR.Currently, we are investigating this phenomenon which mightserve as a novel mechanism for the modulation of geneexpression under adverse conditions. Based on these stu-

dies, another focus of our work is the design of novel antimicrobials to selectively interfere with ribo-some assembly of bacterial pathogens. [email protected]

Protein-deficient ribosomes and novel antimicrobials

Isabella Moll

TeamKonstantin Byrgazov

Anna Kaberdina ChaoSalim Manoharadas

Lena Sokol

Selected Publications Vecerek B. et al. 2007. Control of Fursynthesis by the noncoding RNA RyhBand iron-responsive decoding. EMBO J.26:965-975.

Heidrich N. et al. 2007. In vitro analy-sis of the interaction between thesmall RNA SR1 and its primary targetahrC-RNA. NAR. 35:4331-4346.

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S. pombe cell cycle. DNA and cell wall (upper row) were visualized by DAPI and

aniline blue staining, respectively, and actin(lower row) was visualized by Alexa Fluor

488 Phalloidin staining.

We established an induci-ble expression system for

Drosophila cell culturethat allows the measure-ment of mRNA turnover

rates. Left: Northern blotanalysis of mRNA levels

after a transcriptionalpulse. Right: Quantitativeanalysis of mRNA decay

based on the Northernblot experiments shown

on the left side.

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Post-transcriptional processes such as mRNA degradation,mRNA splicing, translational repression, and RNA-media-ted gene silencing play crucial roles in the regulation ofeukaryotic gene expression. The major focus of ourresearch is the RNA-mediated gene silencing by siRNAs(small interfering RNAs) and miRNAs (micro RNAs). In par-ticular we are interested in understanding the variousmechanisms by which these small non-coding RNAs(siRNAs and miRNAs) regulate gene expression at themolecular level. We use diverse techniques of RNA biochemistry and molecular biology tostudy siRNA- and miRNA-mediated gene silencing in Drosophila cell culture. [email protected]

The regulation of gene expression by small non-coding RNAs

Silke Dorner

TeamIs currently being established.

Selected Publications Eulalio A. et al. 2007. Requirement forenhancers of decapping in miRNA-mediated gene silencing. Genes andDevelopment 21:2558-2570.

Dorner S. et al. 2006. A genomewidescreen for components of the RNAipathway in Drosophila cultured cells.Proc. Natl. Acad. Sci. USA 103:11880-11885.

Cyclophilins are ubiquitous proteins belonging to immunophi-lins, a family of immunosuppressant receptor proteins, whichalso include the FK506 binding proteins and the parvulins.Immunophilins catalyze cis-trans isomerization of peptidebonds preceding proline. Cyclophilins have been implicatedin protein trafficking and maturation, cell signalling, receptorcomplex stabilization, apoptosis, transcription, RNA processing and spliceosome assembly.However, the mechanisms of how cyclophilins contribute to these processes are still largelyunknown. By using combination of biochemical, genetic and cell biology approaches, we are stu-dying regulatory roles of an essential S. pombe multidomain cyclophilin Rct1 in RNA polymerase IItranscription, cell cycle, and chromosome segregation. Identification of cellular pathways in whichRct1 is involved should add newinsights to limited knowledge of howcyclophilins [email protected]

Cyclophilins, multifaceted proteins that regulate diverse cellular processes

Zdravko J.Lorkovic

TeamHana Kautmanova Tatsiana Skrahina

Selected Publication Gullerova M. et al. 2007. Rct1, a nucle-ar RRM-containing cyclophilin, regula-tes phosphorylation of RNA polyme-rase II C-terminal domain. Mol. CellBiol. 27:3601-3611.

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B-Raf is required for ERK activation, in midgestation placenta, butnot in the embryo proper – Immunohistochemistry reveals the pre-sence of active ERK MAPK (brown staining) in E10.5 B-Raf knock-

out embryos and in wild-type placenta (left in the background), butnot in B-Raf-deficient placenta (right in the background). This was

the first demonstration that one of the three Raf kinases is essentialfor ERK activation in a specific organ in vivo.

Research Programme Cell Signaling

Cells survive, proliferate, and differentiate in their environment by interpretingthe signals they receive from it and translating them into the appropriate out-put. If signaling malfunctions or fails, even if only in some cells, the wholeorganism is at risk. The Cell Signaling cluster at MFPL comprises groupsusing a combination of biochemistry, molecular biology, cell biology andgenetics to study cell signaling in experimental systems ranging from yeast toplants to mice.

The Raf/MEK/ERK cascade is a highly conserved signaltransduction module whose activation reportedly results in aplethora of physiological outcomes. Depending on the celltype or the stimulus used, the pathway has been implicatedin proliferation, differentiation, apoptosis, and migration.Because of this wide range of activities, these kinases areconsidered attractive (anticancer) therapeutic targets. However, their essential functions in the con-text of the whole organism are still unknown. Our laboratory is using conditional mutagenesis to defi-ne the essential function(s) and the relevant targets of Raf-1, B-Raf and MEK-1 in in vivo models oforgan development, remodeling, and [email protected]

Biological functions of members of the MAPK signaling cascade

ManuelaBaccarini

TeamFederica Catalanotti Anna Lina Cavallo Karin EhrenreiterGergana Galabova-KovacsMatthias HamerlVeronika JesenbergerFlorian KernGabriele MaurerKatrin MeisslTheodora NiaultJakub RybkaBartosz TarkowskiReiner Wimmer

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Selected Publication Matallanas D. et al. 2007. RASSF1A eli-cits apoptosis through an MST2 path-way directing proapoptotic transcripti-on by the p73 tumor suppressor pro-tein. Mol. Cell 27:962-75.

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Normal yeast cells exposed to osmotic stress: noticethe fast shrinkage of cells followed by recovery to nor-mal cell size (left panels, top to bottom). The rightpanel shows the transient induction of stress specificgenes compared to a constitutive transcript. The graphbelow represents the chromatin state of a stress relatedgene showing rapid eviction of nucleosomes and thesubsequent restoration of their initial repressive pattern(assays by Northern analysis and chromatin immuno-precipitation PCRs for histone H3, respectively). Allchanges are mediated by a p38/MAP kinase path-way.

Speaker Cell SignalingManuela Baccarini

Deputy Speaker Gustav Ammerer

We have been interested in questions how signaling systemsaffect transcription. It was discovered that proline directedkinases such as CDKs or MAPKs can modulate transcriptio-nal induction not only via sequence specific activators andrepressors but also by regulating targets in the general RNApolymerase machinery as well as in the associated chroma-tin remodeling factors. We have focused on two systems inbudding yeast, (1) the expression of mitosis specific genes asan example for proliferative signal responders and (2) geneswhose expression is choreographed by osmotic stress

signals. In both cases we have made progress at specifying the chain of events that determine theexact timing of the transcriptional output. [email protected]

Transcriptional regulation in yeast

The unifying theme is a common and long-standing interest in understanding: • the impact of post-translational modifications and complex formation on the bio-genesis and regulation of signaling networks and of the enzymes they comprise• the feedback mechanisms, both negative and positive, that regulate theactivity within a given signaling network• the mechanisms by which distinct cascades, such as those that signal proli-feration, interact with others signaling differentiation, stress, or inflammation.

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GustavAmmerer

TeamChristina Friedmann

Aleksandra Jovanovic Wolfgang Ludwig Reiter

Jiri Veis Kumar Syam Yelamanchi

Selected Publications Alepuz P. M. et al. 2003. Osmostress-induced transcription by Hot1depends on a Hog1-mediated recruit-ment of the RNA Pol II. EMBO J.22:2433-2442.

Veis J. H. et al. 2007. Activation of theG2/M specific gene CLB2 requiresmultiple cell cycle signals. Mol. CellBiol. 27:8364-8373.

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Crosstalk between SUMO and ubiquitin

Trojan horse strategy inAgrobacterium transformation

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In contrast to animals, plants are sessile organisms and can-not move away from adverse environmental conditions.Therefore, plants heavily rely on high sensitivity detection andappropriate defense and adaptation mechanisms to with-stand changing conditions in its environment. The goals ofour research are to understand the molecular mechanisms of how plants sense, transduce andadapt to adverse various environmental conditions with a specific focus on the interaction of the bac-terial pathogens Agrobacterium tumefaciens, the causative agent of tumour formation in plants, andSalmonella typhimurim, the causative agent of typhoid fever and food poisoning in humans. [email protected]

Host-microbe interactions and innate immunity of plants

Heribert Hirt

TeamAndrij Belokurov Alessandro Carreri Sergio de la Fuente van Bentem Celine Forzani Concetta Giuliani Sarah Himbert Mukesh Kumar Aladár Pettkó-Szandtner Andrea Pitzschke Sebastian Schwarz Astrid Woollard Karin Zwerger

Selected Publication Djamei A. et al. 2007. Trojan horse stra-tegy in Agrobacterium transformationby abusing MAPK defence signalling.Science 318:453-456.

Our group is interested in posttranslational modificationswith ubiquitin and SUMO (small ubiquitin related modifier)which are important regulators for rapid and reversiblechanges in protein function. Modifications occur via ATP-dependent enzymatic cascades including E1, E2 and E3enzymes. The focus of my laboratory is to investigate mecha-nisms regulating SUMO and ubiquitin E2 enzymes and to understand the respective biological con-sequences. This topic is based on our findings that a ubiquitin conjugating enzyme (E2-25K) andalso the sole SUMO conjugating enzyme (Ubc9) are sumoylated. Whereas the sumoylated ubiqui-tin enzyme is severely inhibited in its ubiquitinylation function in vitro (Pichler et al, 2005) the modi-fied SUMO enzyme plays a role in target discrimination (Knipscheer et al submitted). We do notyet understand the biological relevance of E2 sumoylation or how frequently this mechanism is usedto regulate other E2 enzymes. [email protected]

Regulation of SUMO and ubiquitin E2 enzymes

AndreaPichler

TeamHelene Klug Katharina Maderböck Flavia Meireles Canellas de Souza Lisa Kirschner

Selected Publication Pichler A. et al. 2005. Analysis of Su-moylation. SUMO modification of theubiquitin conjugating enzyme E2-25K.Nature Struct. Mol. Biol. 12:264:269.

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Model of PP2A biogenesis in yeast:RRD/PTPA (PP2A phosphatase activa-tor)-dependent generation of activePP2A catalytic C subunit is coupled toholoenzyme assembly (PP2A scaffol-ding A subunit, PP2A regulatory Bsubunit, PP2A methyltransferase,PPM1)

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The Ogris lab studies the biogenesis and regulation of themultisubunit protein phosphatase 2A (PP2A), a highly con-served family of substrate-specific holoenzymes involved inmany different cellular processes including cell cycle regula-tion, signal transduction pathways and programmed cell

death. Our knowledge of PP2A’s role in these processes is still very limited because we lack a dee-per understanding of the molecular mechanisms of PP2A holoenzyme biogenesis in vivo. In a recentstudy we describe how the generation of the active PP2A enzyme, a process that requires thefunctional interaction with an activator protein, is coupled and regulated with PP2A holoenzymeassembly. Our findings led to a novel concept of PP2A biogenesis, in which a tightly controlled acti-vation cascade protects cells from unspecific activity of free catalytic PP2A subunit. We are current-ly investigating the signalling pathways that regulate PP2A [email protected]

Regulation of protein phosphatase biogenesis

Egon Ogris

TeamMartina Mitterhuber

Ingrid Mudrak Marko Roblek

Stefan Schüchner Claudia Stanzel Cornelia Vesely

Selected Publication Hombauer H. et al. 2007. Generation ofactive protein phosphatase 2A is cou-pled to holoenzyme assembly. PLoSBiol. 5:e15.

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In vitro differentiati-on of human ery-

throblasts; brownishstain, hemoglobin;

arrows, enucleatedmature erythrocytes(Leberbauer et al.,

Blood 105, 85)

Histone H3 phosphoacetylation as a markfor gene activation. Induction of the SAP

kinase cascade by stress (mimicked by ani-somycin) or of the MAP kinase cascade bygrowth factors leads to multiple phosphory-

lation events including histone H3-S10phosphorylation. The kinase inhibitor H89

can block this signal transduction.Simultaneous acetylation of neighboring

lysine residues K9 or K14 as result ofincreased affinity for histone acetyltransfe-

rases or changes in the intracellularHAT/HDAC equilibrium by HDAC inhibi-

tors results in phosphoacetylation of histo-ne H3 and gene activation.

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Haematopoiesis starts from stem-cells differentiating into spe-cific lineages and ending with late-stage committed progeni-tors undergoing terminal maturation. Our group focuses onmolecular players critically involved in balancing sustainedproliferation versus terminal differentiation, with particularemphasis on erythropoiesis. We use foetal liver-derivedmouse erythroblasts or myeloid progenitors and variousgenetically modified mouse strains. More recently, weemploy corresponding cells from cord- or peripheral bloodof healthy or diseased human donors.These tools are used to study (i) signalling pathways emana-ting from extracellular ligands like growth factors (stem cell factor, Wnt, erythropoietin) or steroid hor-mones (thyroid hormone, glucocorticoid, androgen); (ii) cell-type specific regulation of iron metabolismduring erythropoiesis and (iii) cell size control, e.g. the decrease in cell volume during erythroid [email protected]

Signal transduction and hematopoiesis / erythropoiesis

Ernst Müllner

TeamMatthias Artaker Helmuth Gehart Marc Kerenyi Manfred Schifrer Ramona Seba

Selected Publications Dolznig H. et al. 2006. Erythroid pro-genitor renewal versus differentiation:genetic evidence for cell autonomous,essential functions of EpoR, Stat5 andthe GR. Oncogene 25:2890-2900.

Schranzhofer M. et al. 2006.Remodeling the regulation of ironmetabolism during erythroid differen-tiation to ensure efficient heme bio-synthesis. Blood 107:4159-4167.

Our group is interested in chromatin modifications and theirrole in gene expression, differentiation and development.One project deals with histone acetylation, a chromatinmodification that is linked to opening of chromatin structuresand associated with important biological processes such astranscription, replication and DNA repair. Reversible acetylation of core histones is controlled byhistone acetyltransferases and histone deacetylases. We focus in our research on histone deacety-lases, enzymes that usually act as transcriptional repressors. We have chosen the mouse as modelsystem and have established an HDAC1 knockout system to analyze in detail the function of thisenzyme in different biological processes. In a second project, we examine the cross-talk betweenhistone acetylation and phosphorylation during the activation of mammalian [email protected]

Chromatin structure and gene expression

ChristianSeiser

TeamAstrid Hagelkruys Sabine Lagger Georg Machat Mircea Winter Stefan Winter Gordin Zupkovitz

Selected Publication Winter S. et al. 2007. 14-3-3 Proteinsrecognize a histone code at histoneH3 and are required for transcriptio-nal activation. EMBO J. 27:88-99.

day 0 day 4 day 6

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(A) BR cellular homeostasis is believed to be regulated eitherby adapting BR biosynthesis (via a feedback regulatory loop)and/or by initiating BR inactivation events. (B) Defects in BRhomeostasis have severe effects on plant development. Adultplants of Arabidopsis thaliana that either over-accumulate BRs(due to altered BR biosynthesis) or are deficient in BRs (due toincreased inactivation) are shown.

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Research interests:1. Microspore embryogenesis and doubled haploids (DH):DHs are an important component of breeding programs ofimportant crops. We have great expertise on DH of tobac-co, rapeseed, wheat, Arabidopsis, snapdragon etc.

2. Mechanism of microspore reprogramming and embryogenesis: One of the major topics of ourgroup is to dissect the mechanism of microspore reprogramming and embryogenesis.3. Gene Targeting in Plants: In flowering plants Gene Targeting (GT) is still inefficient. The main aimof the project is the evaluation of microspores as possibly efficient target for GT. 4. Development of an environment-friendly F1 hybrid breeding technology: The production of F1hybrid requires homozygous parental lines and reversible male sterility. We establish technologythat combines reversible male sterility with DH. [email protected]

Plant developmental genetics and biotechnology

AlisherTouraev

TeamAlexandra Ribarits

Irina Lewicka Tatiana-Elena Resch

Marina Baumann Svitlana Fedchenko

Ekaterina Sidonskaya Katarzyna Szaszka

Irina Sadovnik Maria Granilschikova

Julia Szederkenyi

Selected Publication Forster B. P. et al. 2007. The resurgenceof haploids in higher plants (A review).Trends in Plant Sciences 12:368-375.

Reprogrammed tobaccomicrospores expressing GFPdivide and form embryos

The importance of the steroid hormones brassinosteroids(BRs) in the growth and development of plants is a majorfocus of our research. The BRs function in cell elongation, celldivision and differentiation and are essential in processessuch as germination, development in the light and dark,

senescence and abiotic and biotic stress responses. We are interested in the mechanisms that regu-late BR homeostasis and thereby control their effects. On the one hand we aim to elucidate the con-tribution of catabolic inactivation to the regulation of BR bioactivity. On the other hand we study fac-tors that control BR biosynthesis and/or responses. We use Arabidopsis thaliana as a model and

employ diverse techniques of genetics, molecularbiology, biochemistry and cell biology in our [email protected]

Molecular mechanisms of steroid hormonehomeostasis in plants

BrigittePoppenberger

TeamSigrid Husar

Mamoona Khan Wilfried Rozhon

Merete Tschokert

Selected Publication Poppenberger B. et al. 2005. TheUGT73C5 of Arabidopsis thaliana glu-cosylates brassinosteroids. Proc. Nat.Acad. Sci. USA 102:15253-15258.

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In collaboration with Fritz Kragler’s and Markus Teige’sgroup at MFPL a MAP kinase, AtMPK10, and a MAP kina-se kinase, AtMKK2, have been identified that control flowe-ring time, leaf size and leaf vein formation by interacting withpolar auxin transport inhibitors. In collaboration with AlisherTouraev’s group at MFPL a gene called DCN1 has beencharacterized in tobacco that regulates developmentalphase transitions, including totipotency, and that is involvedin the neddylation of cullins, a component of ubiquitin E3ligases. Colchicine derivates have been synthesized that aremore efficient and less toxic than colchicine as microtubule disrupting and chromosome-doublingagents. Progress has been made in using microspore embryogenesis for gene targeting via homo-logous [email protected]

Plant developmental genetics and biotechnology

ErwinHeberle-Bors

TeamBelogradova Kristina

Kastler Monika

Selected Publications Hosp J. et al. 2007. Transcriptional andmetabolic profiles of stress-induced,embryogenic tobacco microspores.Plant Mol. Biol. 63:137-149.

Ribarits A. et al. 2007. Two tobaccoproline dehydrogenases are differen-tially regulated and play a role inearly plant development. Planta 225:1313-1324.

Expression of the MAP kinase AtMPK10 in hydathodes and leaf veins of transgenic Arabidopsis thaliana plants (blue,center) coincides with auxin maxima (arrows) as reported by expression of the auxin-response gene DR5-GUS (right). Left

image shows leaf development schematically.

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Localisation of stem cells (blue staining) in the Arabidopsis shoot. Theplant contains a b-glucuronidase reporter gene under the control of theWUSCHEL promoter. WUSCHEL is a stem cell specific transcription factorrequired for the control of stem cell pool size.

Histochemical localization of the GUS reporteractivity. The phosphatase AP2C1 promoterfused to GUS is induced by fungus Botrytis cine-rea germination (mock-treated leaf on the left)and after wounding of leaves.

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We aim to understand the molecular mechanisms connec-ting environmental stress factors to responses that enableplant adaptation. We found that PP2C-type phosphatasesprovide important switch off and feedback mechanisms inplants to control stress-activated MAPKs (mitogen-activatedprotein kinases), stress-hormones and plant immunity respon-ses. We are investigating how PP2C phosphatases channelsignalling pathways towards specific responses under bio-tic/abiotic stress conditions and in cell developmental deci-sions. By screening gene expression patterns, plant pheno-types and hormone profiles we apply systemic approaches

to uncover the regulation, localization,interactions and regulatory targets ofPP2C-controlled pathways. [email protected]

Plant PP2C phosphatase functions in environmental and developmental cell signalling

IruteMeskiene

TeamZahra Ayatollahi

Chonnanit Choopayak Julija Umbrasaite

Alois Schweighofer

Selected Publications Michniewicz M. et al. 2007. AntagonisticRegulation of PIN Phosphorylation byPP2A and PINOID Directs Auxin Flux.Cell 130: 1044-1056.

Schweighofer A. et al. 2007b. The PP2C-type Phosphatase AP2C1 NegativelyRegulates MPK4 and MPK6, andModulates Innate Immunity, JasmonicAcid and Ethylene Levels in Arabi-dopsis. Plant Cell 19: 2213-2224.

We are interested in a key question of developmental biolo-gy: how stem cell identity is determined and how the ratiobetween stem cells and differentiating cells is balanced. Tothis end we try to characterize the signalling networks in andbetween cells required to control stem cell turn over in theprocess of plant organ formation. In contrast to animals, plant organ development mainlyoccurs postembryonically and is highly adaptive to the envi-ronment. Moreover differentiated plant cells retain the capa-

city to dedifferentiate to acquire a new cell fate and even to produce a whole new organism. Weuse Arabidopsis thaliana as a model system to elucidate the molecular basis of this developmental

flexibility and to elaborate the conceptual differences to thedeterminate nature of animal [email protected]

Signalling networks in plant cell differentiation

TobiasSieberer

TeamChristine Marizzi Delphine Pitorre Wenwen Huang

Selected Publications Bennett T. et al. 2006. The ArabidopsisMAX Pathway Controls ShootBranching by Regulating AuxinTransport. Current Biology 16:553-563.

Sieberer T. Leyser O. 2006. PlantScience. Auxin transport, but in whichdirection? Science 312:858-860.

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upper left: Tobacco chloroplasts expressingGFP-tagged thioredoxin reductase upper

right: Isolated Arabidopsis chloroplastsafter purification on Percoll gradient

lower: Close-up of chloroplast showing redchlorophyll-autofluorescence and green

GFP signal

28

We study plant’s strategies of adaptation to environmentalchanges or during developmental switches. These proces-ses require a strict regulation and coordination of differentcellular activities, for example coordination of chloroplast-and cellular metabolism. Signalling pathways, which regula-te these events, include MAP kinase cascades (i.e. Teige etal. (2004) Mol. Cell 15, 141-152.) and Ca2+-dependentprotein kinases (CDPKs). Topics to be addressed in the futu-re are (1) cross-talk between MAP kinases and CDPKs,which are activated under similar stress conditions; (2) therole of subcellular localization of CDPKs, mediated by N-Myristoylation; and (3) role of organellar protein kinases.Therefore, we started to analyse a number of CDPKs indetail for their localization, and searched for molecular tar-gets of [email protected]

Plant signal transduction and physiology

Markus Teige

TeamRoman Bayer Andrea Mair Norbert Mehlmer Lander Simon Stael Helga Waltenberger Bernhard Wurzinger

Selected Publications Dóczi R. et al. 2007. MKK3 and MPK7Participate in a Novel Pathogen-Signaling MAP Kinase Pathway inArabidopsis. Plant Cell 19:3266-3279.

Teige M. et al. 2004. The MKK2 path-way mediates cold and salt stresssignalling in Arabidopsis. Mol. Cell15:141-152.

In order to respond and adapt to a changing environmentthe genetic information has to be interpreted properly. Theenvironment is the sum of physical and chemical parametersin the vicinity of a cell. Changes in the environment demandchanges in gene expression. We are investigating howexpression of genes under environmental or stress control isregulated by the interaction of chromatin remodeling com-plexes and transcription factors. S. cerevisiae has been aperfect organism to decipher many fundamental principles.Our interest is to understand how signals reach the genomicDNA and lead to controlled interpretation of the stored infor-mation. We are further investigating the environmentalresponse of the human fungal pathogen Candida glabrata,a organism closely related to yeast but adap-ted to the environment of a mammalian [email protected]

Environmental stress signalling in yeast and pathogenic fungi

ChristophSchüller

TeamEva Klopf Ludmila Paskova Andriy Petryshyn Andreas Roetzer

Selected Publications Schüller C. et al. 2007. Membrane-acti-ve compounds activate the transcripti-on factors Pdr1 and Pdr3 connectingpleiotropic drug resistance and mem-brane lipid homeostasis in saccharomy-ces cerevisiae. Mol. Biol. Cell 18:4932-4944.

Gregori C. et al. 2007. The high-osmo-larity glycerol response pathway inthe human fungal pathogen Candidaglabrata strain ATCC 2001 lacks asignaling branch that operates inbaker’s yeast. Eukaryot Cell 6:1635-1645.

Left: Host versus Pathogen: Candida glabrata (green)inside a Macrophage (with Kovarik Lab). Right: Yeast

cells sense their environment. Proteins move inside stres-sed yeast cells. A transcription factor (Msn2-GFP) moves

to the nucleus to activate protective genes.

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Whereas wild type Arabidopsis plants have oneor a few long shoots that suppress the full out-growth of later emerging shoots in a process cal-led apical dominance (right), all shoots are com-parable in size in plants with defect in a ubiquity-lation complex (left). Fotos by M. Kalda.

Model for the role of EAPP in cell cycleregulation and DNA damage response: EAPP accelerates the cell cycle by stimula-ting E2F activity and modulates the DNAdamage response by interacting with ATM, the Checkpoint kinases 1 and 2, and with p53.

29

My laboratory is focused on the mechanisms controllinggrowth and cell cycle of the mammalian cell. E2F is a familyof transcription factors that integrate cell-cycle progressionwith transcription through cyclical interactions with importantcell cycle regulators, such as the retinoblastoma-tumor-sup-

pressor-gene product (pRB), cyclins and cyclin dependent kinases. We have recently identified andcharacterized an E2F binding protein called EAPP (E2FAssociated PhosphoProtein) that stimulatesE2F-dependent transcription and is found overexpressed in many transformed cell lines. Moreover,EAPP acts as a modulator of the DNA damage response. It interferes with the activity of Chk2(Checkpoint kinase 2) and might be required for checkpoint recovery upon completion of repairprocesses. [email protected]

Cell cycle regulation and DNA damage response

HansRotheneder

TeamPeter Andorfer

Nazanin Najafi

Selected Publication Rotheneder H. et al. 2007. Transcriptionfactors of the E2F family and DNAdamage control. Dynamic Cell Biology1:48-59.

The small modifier protein ubiquitin can be covalently lin-ked to substrates after their synthesis. We are interested inthe protein complexes that mediate ubiquitin attachment tosubstrate proteins in plants. One ubiquitylation complex ofinterest to us operates at the plasma membrane and influ-ences plant growth and architecture. Other ubiquitylationreactions under investigation have roles in cell death pro-grams of plants.Retrotransposons can reverse transcribe their RNA andinsert the cDNA copy into the genome. We have initiateda synthetic biology program to put the plant retrotranspo-

son Tto1 under control of a chemically inducible promoter. Constructs that were successfullytested in Arabidopsis shall be adapted to barley, with the goal to allow insertional mutagenesis

in this crop plant. [email protected]

Protein modification and synthetic biology in plants

AndreasBachmair

TeamKarolin Eifler

Prabhavathi TallojiAndrea Tramontano

Selected Publications Garzón M. et al. 2007. PRT6 /At5g02310 encodes an Arabidopsisubiquitin ligase of the N-end rulepathway with arginine specificity andis not the CER3 locus. FEBS Lett.581:3189-3196

Yin X.- J. et al. 2007. Ubiquitin Lysine 63chain-forming ligases regulate apicaldominance in Arabidopsis. Plant Cell19:1912-1929.

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Domain organizationand electrostatic

potential mapped onthe solvent accessi-

ble surface of theindividual CH

domains of actin bin-ding domain of

alpha-actinin.

Research Programme Structural and Computational Biology

This Programme aims at understanding the structure, function and interacti-ons of biologically important molecules at the atomic, molecular and ultra-molecular levels. It unites experimental and computational disciplines thattackle problems at different levels of resolution: atomic structures and dyna-mic information obtained by X-ray crystallography and NMR, with mediumrange resolution obtained by cellular imaging and light microscopy, andcomputational biology ranging from evolutionary studies to structural bioin-formatics.

Our laboratory is interested in the molecular mechanismsunderlying the actin-based cytoskeleton of the striated mus-cle. The most striking feature of muscle and Z-disc proteinsin particular, is the high frequency of multiple protein-proteininteractions that form part of a complex network. The aim ofour research is to generate detailed structural informationon the protein-protein interaction network in the striated mus-cle Z-disk. To obtain molecular insights we use as the principal techni-que X-ray crystallography in combination with other biophy-sical and biochemical methods available at the Departmentand on the Campus.These activities are complemented by the development of bioinformatics toolsfor results reification and fine tuning of the protein constructs to be structurally [email protected]

Structural biology of cytoskeleton

Kristina DjinovicCarugo

TeamPatrizia Abrusci Mads Beich-Frandsen Oliviero Carugo Bashir Muhammad Khan Sviatlana Kirylava Julius Kostan Suresh Kumar Sofia Macedo Maria Pechlaner Anita Salmazo Claudia Schreiner Kresimir Sikic Björn Sjöblom Andry Volynets

30

Selected Publications Sjekloça L. et al. 2007. Crystal structureof human filamin C domain 23 andsmall angle scattering model for fila-min C 23-24 dimer. J. Mol. Biol.368:1011-1123.

Carugo O. 2007. A structural proteo-mics filter: prediction of the quaterna-ry structural type of hetero-oligomericproteins on the basis of their sequen-ces. J. Appl. Cryst. 40:986-989.

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Speaker Computational and Structural BiologyKristina Djinovic

Deputy Speaker Arndt von Haeseler

The Center for Integrative Bioinformatics Vienna (CIBIV,www.cibiv.at) serves as a central facility to coordinate theBioinformatics activities at the MFPL and the University ofVeterinary Medicine Vienna (VUW). Moreover, it is involvedin providing infrastructure and bioinformatic expertise for thevarious research groups at MFPL and on campus. Thus, it isinvolved in a bunch of collaborations with experimenters. Besides this data analysis part, the CIBIV pursues its own

research agenda. It wants to understand the evolutionary processes that have shaped the genomesof contemporary species. To this end, the CIBIV applies methods from statistics, computer sciences,and mathematics to detect the traces ancient evolutionary events have left in modern genomes.The CIBIV is involved in several international projects, like the Deep Metazoan Phylogeny project,where it coordinates the Bioinformatics aspects (www.deep-phylogeny.org) and the eScience pro-

ject Ontoverse (www.ontoverse.org), where Arndtvon Haeseler is the scientific [email protected]

Unveiling traces of ancient events in contemporary genomes

These approaches are complemented by theoretical, chemical, biochemi-cal, and molecular biological methods. Areas of focus include cell transfor-mation and differentiation, ligand–receptor interactions, RNA and proteindynamics, protein-nucleic acid interactions, and molecules and complexesinvolved in vesicular transport and the F-actin-based cytoskeleton. There is agrowing emphasis on the analysis, interpretation and use of the wealth ofdata swiftly building up from several genome sequencing projects, as wellas on continuous development of computational and experimental methods,where these are critical for scientific progress.

31

Arndt vonHaeseler

TeamQuang Minh Bui

SriHarsha Challapalli Huy Quang Dinh

Ricardo de Matos Simoes Ingo Ebersberger

Gregory Ewing Wolfgang Fischl

Tanja Gesell Martin Grabner

Steffen Klaere Tina Köstler

Anne Kupczok Martina Kutmon

Minh Anh Thi Nguyen Tung Lam Nguyen

Natasa Peric Phuong Minh Pham

Heiko Schmidt Sascha Strauss

Selected PublicationsEbersberger I. et al. 2007. Mappinghuman genetic ancestry. Mol. Biol.Evol. 24:2266-2276.

Laubach T. and von Haeseler A. 2007.TreeSnatcher: Coding trees fromimages. Bioinformatics 23:3384-3385.

Phylogenetic tree of the great apes as inferred from molecular data.

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32

The sequencing of the human genome has provided a ‘partslist’ of the human inventory comprising potential therapeutictargets for the pharmaceutical and biotechnology industry. Inorder to cope with this huge number of targets we introdu-ced a new theoretical conception of protein structural biolo-gy (meta-structure) which can be used for protein sequence-to-function annotation and drug design.A hallmark of our research is the integrative application of this novel conception and sophisticatedNMR spectroscopy directed towards a better understanding of fundamental biological processes.Finally, as much of protein function is predicated on dynamics, we are developing novel methodo-logical approaches which combine biochemistry, bioorganic chemistry and NMR spectroscopy tounravel the microscopic details of functionally important protein [email protected]

Computational chemical biology and biomolecular NMR spectroscopy

Robert Konrat

TeamRenate Auer Bettina Baminger-Schweng Sven Brüschweiler Christof Buchacher Nicolas Courdeville Cornelia Dorigoni Leo Geist Karin Kloiber Agnes Kövari Georg Kontaxis Christoph Kreutz Karin Ledolter Martina Ortbauer Rebby Vie Precilla MariaRosa Quintero Bernabeu Andreas Schedlbauer Sabine Schultes Martin Tollinger Andrea Vavrinska

Selected Publication Baminger B. et al. 2007. Protein-proteininteraction site mapping using NMR-detected mutational scanning. J. Biomol. NMR 38:133-137.

The figure serves as an overview of current-ly pursued research topics in the group. A

central structural biology topic in the groupis the structural analysis of the oncogenic

transcription factor myc and its differentiallyregulated target genes. (Top) We have used

NMR spectroscopy to analyze the C-termi-nal (DNA-binding and dimerization)

domain of myc in the individual stages oftranscription. Additionally our structural ana-

lysis of myc target genes provided a firstglimpse on myc’s cell transforming potential.(Bottom) NMR spectroscopy is a unique toolto identify and analyze high-energy states of

proteins.

The research theme at the Mathematics and BiosciencesGroup Vienna (MaBS, www.mabs.at) is the mathematicalbiology of evolution. Evolution is the unifying theory of thebiological sciences, and our aim is to design advancedmathematical methods and models that account for the bio-logical complexity involved in most evolutionary processes. Complexity arises on all levels of biolo-gical organization: molecular, organismal, and ecological. The key issues of evolutionary research,such as adaptation and speciation, are usually addressed in special sub-disciplines for each ofthese levels, i.e. molecular population genetics, quantitative genetics, and evolutionary ecology. Wework on all three fields with the special goal to create an integrative approach, using a combinati-on of different models, concepts, and [email protected]

Evolutionary theory of adaptation and speciation

JoachimHermisson

TeamMichael Kopp

MaBS members at Faculty of Mathematics

Claus RuefflerClaudia BankHannes SvardalAgnes Rettelbach

Selected Publication Kopp M., Hermisson J. 2007. Adapta-tion of a quantitative trait to a movingoptimum. Genetics 176:715-719.

In a theoretical study, Michael Kopp and JoachimHermisson investigated whether adaptation of a

population to a gradually changing environment ismore likely to occur in small or large evolutionarysteps (i.e. substitutions of adaptive mutations). Theanswer to this question critically depends on two

parameters: the mutation rate (?) and the speed ofthe environmental change (v). The Figure shows theprobability (termed ?small) that the next step in the“adaptive walk” is a small one. Depending on the

above parameters, the model predicts three qualita-tively different regimes (termed the fixation time-limi-

ted, mutation-limited and environmentally-limitedregimes), in which this probability is either low, inter-

mediate or high. For example, evolutionary stepsare most likely to be small if the environment

changes slowly and the population is supplied withsufficiently many appropriate mutations.

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Model for the uptake of inert, 25nm – particles in cells: Fast trans-location was observed and cha-racterized for such small, artificialparticles, which is mechanisticallydifferent to uptake and processingof viruses or peptides also studiedrecently.

Principle of Thin-film Sensor

33

Biophysical characterization of biomolecules and of thereinteractions in solution as well as on a live cell level repre-sents the main object of our research. Methods include fluo-rescence and time resolved techniques performed over awide range of time resolution. Studies by optical spectrosco-py are complemented by biocalorimetry (DSC).Quantitative studies on molecular dynamics on a single

molecule level are performed using advanced fluorescence correlation techniques. Among others,they are applied on studies of ligand – receptor interactions relevant for hormone regulation andthe mechanisms of endocytosis and transport in single living cells. These measurements provide thebasis for mathematical modelling of complex dynamic behaviour in bio-systems, implemented inclose cooperation with other research [email protected]

Biomolecular optical spectroscopy

GottfriedKöhler

TeamMichael Edetsberger

Erwin Gaubitzer Gottfried Grabner

Ajok Jha Raphaela Kaisler

Martin Knapp Dominik Rünzler Julia Schindelar

Selected Publication Steiger C. et al. 2007. Multi-modularReceptor Binding to an IcosahedralVirus: Determination of BindingConstants by Fluorescence CorrelationSpectroscopy. Biochemistry 46:6331-6339.

We are an interdisciplinary group at the University of Viennainvolved in basic and applied research. We are interested inchemical engineering of biomolecules and their applicationin biosensors, bioreactors and drug targeting. Beyond thatwe are interested in establishing new, miniaturized test-kits foruse in clinical chemistry – human as well as veterinarian, bedside monitoring and environmental chemistry employing newnanotechnological principles and biorecognition. We arefurther involved in basic research concerning unknown stepsin metabolism, chemotaxis and substance targeting to get abetter knowledge on certain diseases (e.g. botulism, cray

fish plague, …) and on the metabolic way of life of cells from various organisms (microorganismsand animal cells). We are also working on various aspects dealing with food allergy. Beyond that

a new biosensorchip formeat decay is under [email protected]

Biosensors and chemical engineering of biomolecules

Fritz Pittner

TeamHaifa Al-Dubai

Margit Barth Helmut Hinterwirth Nadira Ibrisimovic

Irene Maier Georg Oberhofer

Martina Strobl

Selected Publications Hohensinner V. et al. 2007. A ‘gold clu-ster-linked immunosorbent assay’:Optical near field biosensor chip forthe detection of allergenic ß-lactoglo-bulin in processed milk matrices.J. Biotechnol. 130:385-388.

Bauer M. and Pittner F. 2007. Opticalsensor and method for indicating theage or quality of a natural product.WO 2007/144367 A1.

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Rec8, is a meiosis specific cohesin atthe basis of the chromosome axis,

required for meiotic recombinationand sister chromatid cohesion. Its

chromosomal associations (A, resolu-tion: 100nucleotides) differentiates

the chromosome into core and loopregions (visualized in B). Note how

the centromere is surrounded bymighty cohesin signals, which help to

resist spindle forces in the secondmeiotic division, while arm cohesin is

discarded during the first division.

Research ProgrammeChromosome Biology

Proteins which determine the architecture of eukaryotic chromosomes also cri-tically influence many of their key features, such as regulation of gene expres-sion through chromatin modification, DNA repair and faithful segregationupon cell division. The Chromosome Biology cluster studies these aspects.

A special focus is directed towards chromosome behavior in meiosis, a spe-cialized cell division essential to generate haploid germ cells from diploidsoma for sexual reproduction. Several meiotic mechanisms diverge from themitotic scheme to ensure that reduction of the diploid chromosome set inmeiosis produces complete haploid sets. Meiotic chromosomes "recognize"their homologous partner by a DNA repair based mechanism, pair and thenbecome physically linked with their partners to follow a different segregationpattern than during mitosis. Obviously, such processes are central for the fer-

While meiotic mother cells carry two copies of each chromo-some, meiotic daughter cells possess exactly one copy (eit-her maternal or paternal) of each parental allele. The transi-tion between these cellular states is accomplished by aremarkable chromosome sorting and distribution processduring meiosis, which requires the programmed appearanceof DNA-double strand breaks. Repair of these programmed lesions allows for recognition and fortemporal linkage of corresponding chromosomes (the homologs), a prerequisite for correct separa-tion of paternal and maternal alleles. Currently we concentrate on defining where exactly structuraland recombination proteins interact with chromosomal DNA in vivo during meiosis. The figure showshow Rec8, an axis protein, associates with certain chromosomal positions, preferably close to thecentromere, separating the chromosome into loop and core regions. The paper of (Uanschou,Siwiec et al. 2007), a collaboration with a strong contribution from the Schlögelhofer group, showsfunctional conservation in higher eukaryotes of a key recombination gene (Com1) that we had ear-lier discovered in [email protected]

Chromosome structure and recombination in yeast meiosis

Franz Klein

TeamBenjamin Brenhoffer Jean Mbogning Marco Antonio Mendozza-Parra Silvia Panizza Alexander Woglar Martin Xaver

34

Selected Publication Uanschou C. et al. 2007. A novel plantgene essential for meiosis is related tothe human CtIP and the yeastCOM1/SAE2 gene. EMBO J. 26:5061-5070.

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Wild-type cells faithfullysegregate their chromo-somes as visualized byGFP-labeled chromoso-me I during anaphase(left). We have identi-fied S. pombe mutantswhich missegregatechromosomes (right).Studying such mutants isessential for understan-ding of the mechanismwhich governs chromo-some segregation.

Speaker Chromosome Biology Franz Klein

Deputy Speaker Michael Jantsch (RNA Biology)

How does the cell ensure that during cell division eachdaughter cell inherits one copy of every chromosome?Meiosis is a specialized cell division which produces haploidgametes from diploid cells, how is this reduction of chromoso-me number achieved? We want to understand how cells accu-rately segregate their chromosomes during mitosis and meio-sis. It is important to understand this process because defectsin chromosome segregation (missegregation) during mitosisresult in cells with abnormal number of chromosomes. Suchcells are hallmarks of cancer. Defects during meiosis cause mis-carriages, infertility and genetic diseases such as Down’s

Syndrome. In our studies we use the fission yeast S. pombe which is an excellent model organismamenable to both genetic and cell biology techniques. [email protected]

Chromosome segregation during mitosis and meiosis

tility of higher organisms. But, beyond that, meiotic chromosomes have suc-cessfully served to study recombinational repair, because it occurs in a fre-quent and programmed way in most organisms. By studying recombinationon meiotic chromosomes, genes and mechanisms highly relevant for genomemaintenance and carcinogenesis have been discovered.

The Chromosome Biology cluster aims to increase our understanding of chro-mosome function by comparative analysis of chromatin architecture, recombi-nation, pairing and segregation in a synopsis of several model organisms.Recently adopted strategies include the dynamic and high resolution map-ping of protein-chromosome interactions in vivo, as well as developing bio-chemical tools to reveal protein interactions and modifications during meiosisand mitosis.

35

Juro Gregan

TeamCornelia Rumpf

Zhiming Chen Lubos Cipak

Selected Publications Gregan J. et al. 2007. The kinetochoreproteins Pcs1 and Mde4 and hetero-chromatin are required to preventmerotelic orientation. Current Biology17:1190-1201.

Novel genes required for meioticchromosome segregation are identi-fied by a high-throughput knockoutscreen in fission yeast. Current Biology15:1663-1669.

normal segregation

chromosome I DNA tubulin

missegregation

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In Pachytene homologous parental chromosomes are connected by a pro-teinacious structure, the synaptonemal complex (SYP-1 in red). HIM-8 (ingreen) highlights the chromosome end of the X chromosome and the two

signals from the parental chromosomes coalesce into one.

Two conjugating cells of the ciliate Tetrahymena with extreme-ly elongated meiotic micronuclei. Green foci are aggregatesof the recombination protein Rad51 at sites of ongoing meio-

tic recombination. Non-meiotic macronuclei are depicted inblue. Tetrahymena is an organism with a strongly derived

meiosis.

36

Cells of sexually reproducing eukaryotes normally containtwo equal (homologous) sets of chromosomes, one contribu-ted by the father, the other by the mother during the fusion ofgametes and the formation of a zygote. When eggs orsperm are produced, they must be furnished with a single setof chromosomes. Therefore, germ progenitor cells undergo areductional division, meiosis. During meiosis, homologouschromosomes of paternal and maternal origin pair,exchange parts and segregate to different daughter nuclei.Our group is comparing various aspects of meiotic chromo-some organization and behaviour in yeasts, nematodes and ciliates to fully exploit the wealth ofvariability displayed by the meiotic processes in some of the more exotic organisms. This will servethe final goal to learn about the origin of conserved meiotic features such as the synaptonemal com-plex, the chromosomal bouquet, and finally, theevolution of meiosis [email protected]

Meiotic chromosome pairing

Josef Loidl

TeamAnna Estreicher Agnieszka Lukaszewicz Mario Spirek

Selected Publications Penkner A. et al. 2007. A conservedfunction for a C. elegansCom1/Sae2/CtIP protein homologuein meiotic recombination. EMBO J.26:5071-5082.

Lorenz A. et al. 2006. Meiotic recombi-nation proteins localize to linear ele-ments in Schizosaccharomyces pombe.Chromosoma 115:330-340.

Meiosis is the specialized cell division that generateshaploid germ cells. It not only halves the chromosome con-tent but also ensures genetic diversity by recombination.Defects in meiosis lead to unfaithful chromosome segregati-on and are thus the major cause for miscarriages and birthdefects. For proper chromosome segregation in meiosis I,homologous chromosomes have to recognize each other,pair, synapse and recombine entailing a physical connectionof the bivalents. The question how homologous chromoso-mes recognize each other in the first place and establish theprimary contact is a main focus of our studies.We use the genetic model system C. elegans to identifygenes that are essential for faithful meiotic [email protected]

Meiosis in C. elegans

Verena Jantsch-Plunger

TeamAntoine Baudrimont Jiradet Gloggnitzer Margot Hulek Markus Ladurner Thomas Machacek Yasmine MamnunAlexandra Penkner Christian Pflügl Lois Tang

Selected Publications Penkner A. et al. 2007. The nuclearenvelope protein matefin/SUN-1 isrequired for homologous pairing in C.elegans meiosis. Developmental Cell12:873-885.

Penkner A. et al. 2007. A conservedfunction for a C. elegans Com1/Sae2/CtIP protein homologue in meioticrecombination. EMBO J. 26:5071-5082.

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The figure contains a compilation of picturesfrom the publication Uanschou et al. 2007,and shows phenotypes and cytological ana-lyses of wild-type (A - D) and Atcom1mutant plants (E - H). Panels A and E showfruit bodies of mature plants. Panels B and Fshow meiotic chromosomes in a fluorescentin situ hybridisation experiment. Panels Cand G display meiotic chromosomes(green) additionally visualising a recombi-nation protein (red) and panels D and Hshow the accumulation of the SPO11-1 pro-tein (red) in Atcom1 mutant plants on meio-tic chromatin (blue).

37

The focus of research is meiotic recombination in the modelorganism Arabidopsis thaliana. Meiosis is a specialised celldivision that ensures the reduction of the genome prior to theformation of generative cells. During meiosis, novel combina-tions between parts of paternal and maternal chromosomesare generated through the process of homologous recombi-nation (HR). A pre-requisite for HR are DNA double strandbreaks (DSBs), generated by a protein complex with the con-served protein SPO11 being its catalytically active subunit.DSBs are formed at non-random sites throughout the geno-

me, known as hot spots of meiotic recombination. We are interested in cis and trans acting factorsthat mediate meiotic DSB formation and subsequent DNA repair. [email protected]

Meiotic recombination in Arabidopsis thaliana

PeterSchlögelhofer

TeamBernd Edlinger

Fritz Hunger Michael Janisiw

Marie-Therese Kurzbauer Rene Ladurner Stefan Mevius

Tanja Siwiec Clemens Uanschou

Selected Publications Vignard J. et al. 2007. The interplay ofRecA-related proteins and the MND1-HOP2 complex during meiosis inArabidopsis thaliana. PLoS Genet.3:1894-1906.

Uanschou C. et al. 2007. A novel plantgene essential for meiosis is related tothe human CtIP and the yeast COM1/SAE2 gene. EMBO J. 26:5061-5070.

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Early in the cell cycle (top panel) the old Golgi (G; red) in T. brucei islocated near to one lobe of a bi-lobe structure (green, closed arrowhe-

ads). Later in the cell cycle (bottom panel) the new Golgi is found asso-ciated with the other lobe suggesting that the bi-lobe has a role to play in

the duplication process. N=nucleus; K=kinetoplast (mitDNA); openarrowheads=basal bodies.

Research Programme Membranes and the Cytoskeleton

The most striking feature of eukaryotic cells is the sub-division of the cytoplasmby intracellular membranes, generating distinct compartments that each carryout specialised cellular functions. These compartments, or organelles, rangefrom nuclei involved in DNA replication and gene expression, to energy-pro-ducing mitochondria and detoxifying peroxisomes, through to the series ofcompartments that characterise the exo- and endocytic pathways.Lipoproteins, for example, are assembled along the exocytic pathway in cellssuch as hepatocytes, and then endocytosed by other cells, most notably thedeveloping chick oocyte, which stores them as a nutrient source for subse-quent development of the embryo.

Membrane-bound organelles are intimately connected with cyto- and nucleos-keletal elements which not only help to stabilize their morphology and determi-

The Golgi apparatus lies at the heart of the secretory path-way receiving the entire output of newly-synthesized proteinsand lipids from the endoplasmic reticulum, purifying and pro-cessing them before sorting to their correct destination. Newcopies of the Golgi need to be made during each cell cycle,to ensure inheritance through successive generations. Westudy this process in the protozoan parasite Trypanosomabrucei, which has a highly simplified secretory pathway anda single Golgi, and permits manipulations not possible inother organisms. So far we have identified a novel bi-lobestructure needed for Golgi duplication and have worked outthe order in which components are assembled into a wor-king Golgi. [email protected]

Biogenesis of the Golgi apparatus

GrahamWarren

TeamChris de Graffenried Lars Demmel Thomas Gniadek Martina Gschirtz Brooke Morriswood Marco Sealey

38

Selected Publications Ho H. H. et al. 2006. Ordered assemblyof the duplicating Golgi in Trypa-nosoma brucei. Proc. Natl. Acad. Sci.USA 103:7676-7681.

He C. Y. et al. 2005. Golgi duplicationin Trypanosoma brucei requiresCentrin2. Science 310:1196-1198.

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Major tools and techniques used in the lab. A) Knockout mice. B)Primary cell cultures derived from wild-type and mutant mice. A tri-ple-stained fibroblast cell visualized by confocal laser microscopy isshown. Red, tubulin; green, vimentin; blue, plectin isoform 1f. C)Electron microscopy of double immunogold-labeled mouse myofi-brils. Large particles, β-dystroglycan; small particles, plectin. D)Visualization of microtubule network arrays in muscle fibers indivi-dually isolated by teasing of skeletal muscle tissue.

Speaker Membranes and the CytoskeletonGraham Warren

Deputy Speaker Gerhard Wiche

The cytoskeleton provides the structural basis for rigidity, shape,movement and intracellular dynamics of eukaryotic cells. Some25 years ago the group discovered, and extensively characte-rized a ubiquitous cytoskeletal protein (plectin) of gigantic sizethat became the prototype of what meanwhile is a large fami-ly of similar proteins, collectively called cytolinkers. Plectin haskey functions in cellular cytoarchitecture, positioning of organel-les, mechanical stabilization, and signal transduction, includingnerve conduction. Thus, disorders in plectin lead to diseasesaffecting a variety of cell types and tissues. The group is studying the function of plectin and other cytolinkers

using transgenic mouse models to mimic human disease. Major current research topics comprise molecu-lar mechanisms underlying plectin-related muscular dystrophies and neuropathies, gene therapy for plec-tin-inflicted epidermal disorders, and plectin-dependent stress response (signaling) of endothelial [email protected]

The cytoskeleton in development, stress response, and disease

ne their position within a cell, but are also involved in helping them to carry outtheir specific functions. Cytoskeletal elements and related nuclear proteins alsodetermine cell shape and are responsible for the radical and dynamic changesin shape that occur during cell locomotion and chromosome segregation.There is also an intimate relationship between organelles and the cytoskeletonduring proliferation and differentiation, when organelles transiently disassembleor undergo duplication in preparation for partitioning during cell division.

The groups within this research programme cover a range of membrane,cytoskeletal and nuclear proteins, and systems, aimed at understanding basicmechanisms as well as what goes wrong during the many disease processesthat are known to result from defects in these proteins or when membrane-cytoskeletal interactions are impaired.

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GerhardWiche

TeamGerald Burgstaller

Irmgard Fischer Peter Fuchs

Rocio G. C. ValenciaMartin Gregor

Marianne RaithSiegrfried Reipert

Günther RezniczekNevena Vukasinovic

Gernot WalkoAurora Zuzuarregui

Selected PublicationsRezniczek G. A. et al. 2007. Plectin 1fscaffolding at the sarcolemma of dys-trophic (mdx) muscle fibers throughmultiple interactions with β-dystrogly-can. Journal of Cell Biology 176:965-977.

Osmanagic-Myers S. et al. 2006. Plectin-controlled keratin cytoarchitectureaffects MAP kinases involved in cellu-lar stress response and migration.Journal of Cell Biology 174:557-568.

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Yeast mitochondria visualized by green fluorescent protein directed to the organelle

and visualized by confocal microscopy (a-b)and electron microscopy (c-d). Left: mitochondri-

al network typical of wild-type cells Right: frag-mented mitochondria resulting from osmotic

swelling upon loss of K+/H+ exchange activity.

Knockout of the lamin binding protein LAP2α inmice causes epidermal hyperplasia (a), increasedproliferation of epidermal progenitor cells (b), andtranslocation of lamin from the nucleoplasm to thenuclear periphery (c). Histological epidermis secti-

ons (hematoxylin/eosin stained, a) and immuno-fluorescence microcraphs of the epidermis stained

for proliferation markers (KI67, b) and lamin (c)are shown.

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Lamins are major structural components in the nucleus of mul-ticellular eukaryotes. They form a network that mechanicallysupports the nuclear envelope and organizes higher orderchromatin structure. In recent years, mutations in lamins havebeen found to cause human diseases with different patholo-gies, ranging from muscular dystrophy, to premature agingsyndromes. The molecular pathways leading to these disea-ses are poorly understood. Using transgenic mouse modelsand cultured cells we study novel functions of lamins in geneexpression and signalling and their potential impairment inlamin-linked diseases. We also focus on the involvement of lamin-binding proteins, which are key fac-tors regulating lamin assembly and function. We propose that lamins have important functions incontrolling adult stem cells during tissue homeostasis and regeneration. [email protected]

Lamins in nuclear organization and human diseases

RolandFoisner

TeamKatarzyna Biadasiewicz Mirta Boban Andreas Brachner Juliane Braun Barbara Bublava Andreas Eger Martha Garstkiewicz Ivana Gotic Josef Gotzmann Nana Naetar Ursula Pilat Aneesa Sultan

Selected Publications Dorner D. et al. 2006. Lamina-associa-ted polypeptide 2· regulates cell cycleprogression and differentiation viathe retinoblastoma-E2F pathway.J. Cell Biol. 173:83-93.

Naetar N. et al. 2007. LAP2alpha-bin-ding protein LINT-25 is a novel chro-matin-associated protein involved incell cycle exit. J. Cell Sci. 120:737-747.

Metal ions are known to be of prime importance for many cel-lular functions including volume control of cells and organelles,membrane integrity, free radical homeostasis or differentiationprocesses and they act as co-factors of many essential enzy-mes. Failure to maintain appropriate levels of metal ions inhumans is a feature of hereditary and acquired disorders.Genes encoding proteins for cation homeostasis in mitochon-dria remained unknown until recently when we identified genesfor the transport of magnesium (Mg2+), iron (Fe2+) and potas-sium (K+). We are studying structure and function of the respec-tive proteins as well as effects of various gene mutations in the yeast Saccharomyces cerevisiae and inhuman cells. This involves collaboration with K. Djinovic (protein stucture, MFPL Vienna) and C. Romanin(electrophysiology, Univ. Linz). [email protected]

Metal ion homeostasis in mitochondria

RudolfSchweyen

TeamMichael Aichinger Markus Aleschko Johanna Fischer Elisabeth Froschauer Anton Graschopf Tamás Henics Dagmar Hosiner Mirjana Iliev Karin Nowikovsky Gerhard Sponder Jochen Stadler Sona Svidova

Selected PublicationsSchindl R. et al. 2007. Mrs2p forms ahigh conductance Mg2+ -selectivechannel in mitochondria. Biophys J.93:3872-3883.

Nowikovsky K. et al. 2007. Mdm38 pro-tein depletion causes loss of mitochon-drial K+/H+ exchange activity, osmo-tic swelling and mitophagy. Cell DeathDifferentiation 14:1647-1656.

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Ablation of ApoER2 and VLDL receptor in mice leads to total loss of therostral migratory stream and accumulation of neuroblasts in the subventri-cular zone. Sagittal sections of the forebrains of mice at P17 were stainedwith hematoxylin. Scale bars correspond to 500 mm.

VLDL particles in coated structures of oocytes. Themechanism of clathrin-mediated endocytosis wasdiscovered in oocytes in 1964. The electron micro-praph shows serum-derived lipoprotein particles(VLDL) in clathrin-coated pits (c.p.) being internali-zed via invagination and pinching-off of coatedvesicles (c.v.) in a chicken oocyte. The receptorgene family involved has been extensively charac-terized in my group.

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With emphasis on receptor-mediated endocytic processes,we investigate molecular genetic, cell biological, and bio-chemical details of (i) oocyte growth and chick embryodevelopment, with focus on lipoprotein transport via the lowdensity lipoprotein (LDL) receptor gene family, (ii) avian lipa-ses and transfer proteins (i.e., the lipolytic proteome) of thegranulosa cells surrounding the oocyte as well as of theextraembryonic yolk sac, which mediate yolk lipid depositi-on and subsequent utilization by the embryo, respectively,(iii) the molecular genetic basis for human atherosclerosis

caused by single-gene mutations that reduce or abolish receptor-mediated transport of lipoproteinsand/or cholesterol, and (iv) the role of the recently discovered apolipoprotein, apo-AV, in the etio-logy of human pathological hypertriglyceridemia. [email protected]

Defects in receptors as causes of Atherosclerosis and failing fertility

WolfgangSchneider

TeamAndrea Dichlberger

Barbara Riegler Melanie Schiff

Gernot Hirn Raimund Bauer

Stefanie Schlager Mary-Rose Espina

Selected Publications Hummel S. et al. 2007. Identification ofa novel chondroitinsulfated collagen inthe membrane separating theca andgranulosa cells in chicken ovarian folli-cles. J. Biol. Chem. 282:8011–8018.

Dichlberger A. et al. 2007. Avian Apoli-poprotein A-V binds to LDL receptorgene family members. J. Lipid Res.48:1451-1456.

We study the biology of LDL receptor related proteins, agroup of cell surface receptors which mediate transport ofmacromolecules across cell membranes and play importantroles in signal transduction. The biological systems we focuson are the chicken oocyte and the mammalian brain.Oocyte growth is promoted by the uptake of yolk precursorsmediated by the VLDL receptor. In the developing mammali-an brain newborn neurons have to migrate to their final loca-tion. This process is governed by the Reelin signaling path-way, which is mediated by the VLDL receptor and [email protected]

Macromolecular transport across cell membranes

JohannesNimpf

TeamSophia Blake

Sarah Duit Harald Rumpler

Selected Publications Fayad T. et al. 2007. Low-density lipo-protein receptor-related 8 (LRP8) isupregulated in granulosa cells of bovi-ne dominant follicle: molecular charac-terization and spatio-temporal expres-sion studies. Biol. Reprod. 76:466-475.

Andrade N. et al. 2007. ApoER2/VLDLreceptor and Dab1 in the rostralmigratory stream function in postna-tal migration independently of Reelin.Proc. Natl. Acad. Sci. 104:8508-8513.

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Confocal laser scanningmicroscopy images of plantsexpressing a fluorescent fusi-on protein which is transpor-ted into the nucleus (green;upper right) and alters cellcycle progression (large tri-

chomes; lower right) and thefunction of homeodomain

proteins involved in meristem(= plant stem cells) mainten-

ance (lower left).

Components of the cytoskeleton (the microtubule-associa-ted protein MAP1B in red, 1st column, and tubulin in

green, 2nd column) co-localise in cultured primary neuronsof the mouse (yellow, 3rd column), depending on the

growth state of the axon. Our work suggests, that increa-sed binding of MAP1B to microtubules induces axon

retraction and sinusoidal microtubule bundles (middle row),whereas at the tip of growing axons (top and bottom row)microtubules are splayed and MAP1B is partially removed

from microtubules and also found in the cytoplasm best visi-ble in the bottom row.

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Axon extension, axon branching, and axon retraction aremajor morphological changes that neurons have to executeto accomplish correct wiring of the nervous system duringdevelopment and during regeneration after injury. Thesetransformations are guided by extracellular signals which ulti-mately need to be translated into the rearrangement of theneuronal cytoskeleton. We study signalling mechanisms and posttranslational modifications of micro-tubule-associated proteins and other components of the cytoskeleton that regulate the orchestratedreorganisation of microtubules and actin in response to extracellular signals. Our approach combi-nes gene ablation in the mouse with cell biological and molecular analyses in cultured neurons andother primary [email protected]

Cytoskeleton regulation in morphogenesis and axon guidance

FriedrichPropst

TeamLuise Descovich Ilse Kalny Ewa Krupa Waltraud Kutschera

Selected Publication Stroissnigg H. et al. 2007. S-nitrosylati-on of microtubule-associated protein1B mediates nitric-oxide-induced axonretraction. Nat. Cell Biol. 9:1035-1045.

In plants initiation and/or maintenance of meristems (stemcells) depends on a class of homedomain transcription fac-tors. It was shown that homeodomain proteins such asKNOTTED1 and STM are essential for meristem formationand move with their mRNA from cell to cell via intercellularpores named plasmodesmata. This intercellular transportsystem, which is also used by viruses to spread throughoutthe plant body, is tightly regulated and mediated by plasmo-desmatal components. Our work focuses on the eventsunderlying the intercellular transport, the isolation/characte-rization of the cellular machinery regulating cell-to-cell trans-fer, and the function of non-cell-autonomous transcription fac-tors and [email protected]

Intercellular transport of proteins and RNAs regulating cell-fate

Fritz Kragler

TeamDaniela Fichtenbauer Kornelija Pranjic Nikola Winter

Selected Publication Winter N. et al. 2007. MPB2C, a micro-tubule-associated protein, regulatesnon-cell autonomy of the homeodo-main protein KNOTTED1. Plant Cell19:3001-3018.

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Artificial recon-struction of ayeast cellexpressing afluorescent pero-xisomal protein

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Our research is focussed on the origin of peroxisomes andthe molecular mechanism of their biogenesis. These single-membrane bound organelles are ubiquitous, highly versatilecompartments in eukaryotic cells and are involved in manymetabolic processes, such as degradation of fatty acids. Anetwork of interacting proteins guarantees the biogenesis offunctional peroxisomes, the transport of peroxisomal matrixproteins across the organellar membrane, and the control ofsize, shape and number of these compartments. Impaired

peroxisome biogenesis leads to cytosolic mis-localization of peroxisomal processes. Employingyeast as model system we aim to elucidate the protein composition of mature peroxisomes and pre-cursor structures and the functional role of the proteins [email protected]

Origin and biogenesis of peroxisomes

AndreasHartig

TeamVeerle De Wever

Karin Großschopf Anja Huber

Selected Publications Brocard C. and Hartig A. 2007. Peroxins:A Proliferation Romance amongstSupposition and Disposition. SpecialFeature in Dynamic Cell Biology 1:1-11.

Kunze M. et al. 2006. A central role forthe peroxisomal membrane in glyoxy-late cycle function. Biochim. Biophys.Acta 1763:1441-1452.

How do membranes proliferate and acquire their shape?Our team focuses on elucidating the molecular dynamics ofmembrane proliferation and the function of membrane pro-teins involved in this process. To preserve cellular fitness, pro-liferation of cellular compartments, the organelles, needs tobe tightly regulated. Accordingly, organelle malfunction is cri-tically involved in the development of devastating humandiseases. Peroxisome function includes lipid metabolism.These organelles possibly contribute to cellular oxidativestress through their ability to generate and degrade hydrogen

peroxide and other reactive oxygen species, which may connect their function to the process ofaging. We employ biochemical and cell biological approaches in yeast and human cells and carryon oxidative stress studies to grasp the molecular mechanism governing peroxisome proliferation. [email protected]

Dynamics of protein assembly at the peroxisome membrane in yeast and human cells

Cécile BrocardElise-Richter

Prize Holder

TeamSophie Merich

Johannes-P. Koch

Selected Publications Brocard C. and Hartig A. 2007. Peroxins:A Proliferation Romance amongstSupposition and Disposition. SpecialFeature in Dynamic Cell Biology 1:1-11.

De Wever V. et al. 2005. A Dual Rolefor PP1 in Shaping the Msn2-Dependent Transcriptional Responseto Glucose Starvation. EMBO J.24:4115-4123.

Picture: Laser Scanning Confocal Microscopy pictures showing normal (left) and abnormally enlarged peroxisomes (right)in human embryonic kidney cells. The upper left corners show three-dimensional reconstitutions of chosen parts for eachpicture as indicated.

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Cyanophora paradoxa,Glaucocystophyta:

Immuno-EM of a dividing cyanelle:Primary antibodies directed against

peptidoglycan from E. coli. Gold particles sdectorate the unique organel-

le wall. CB, central body (putative carboxysome).

Hepato-oocyte-embryo axis for yolk transportand utilization. During oogenesis in the chicken,the yolk precursors (e.g., vitellogenin and VLDL)

are synthesized by the maternal liver under strin-gent hormonal control (E2) and taken up intothe oocyte via receptor-mediated endocytosis(LRs). After ovulation and fertilization, a major

feature of development is the formation of aseries of extraembryonic structures including the

amnion, chorion, allantois and the yolk sac. Amajor role of the yolk sac is the uptake of

nutrients from the yolk, their degradation and/ormodification for re-synthesis and secretion into

the embryonic circulation.

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We focus on the biology of the growing chicken oocyte andthe yolk sac as organ for nutrient transfer from yolk to the deve-loping chick embryo. Specifically, we are interested in unravel-ling molecular mechanisms involved in the transport of VLDL tothe oocyte and from the egg yolk to the embryo proper. In thiscontext, the roles of the LDL receptor gene family members,apolipoproteins, and extracellular matrix proteins are investiga-ted. Furthermore, we focus on the roles of oxidative modificati-ons of LDL in early onset of atherosclerosis. We are interestedin identifying synthetic and natural compounds with the poten-tial to act as catalysts or inhibitors of theatherogenic modifications of [email protected]

Lipoproteins in development and disease

MarcelaHermann

TeamJulia Plieschnig Desiree Raich Birgit Nikolay Michaela Rathberger

Selected Publications Hermann M. et al. 2000. Lipoproteinreceptors in extraembryonic tissues ofthe chicken. J. Biol. Chem. 275:16837-16844.

Laggner H. et al. 2007. The novel gase-ous vasorelaxant hydrogen sulfideinhibits angiotensin-converting enzy-me activity of endothelial cells.J. Hypertens. 25:2100-2104.

We are interested in the biochemistry, molecular and cellbiology of cyanelles. These peculiar plastids are found onlyin glaucocystophyte algae. Their unique peptidoglycan walland the postulated carboxysome (both features are otherwi-se confined to prokaryotes) render them a “missing link” ofplastid evolution and an extant proof of the endosymbiotictheory. The data and results we generated working with the“living fossil” Cyanophora paradoxa support the concept ofa single primary endosymbiotic event leading to phototro-phic eukaryotes: This enormously complicated processdating back approximately 1.5 billion years happened only once, i.e. between a certain type ofheterotrophic eukaryotic host and a certain cyanobacterial species. Thus the kingdom “Plantae” canbe considered as [email protected]

The cyanelles of the ”living fossil“ Cyanophora paradoxa

WolfgangLöffelhardt

TeamSara Fathinejad Jürgen-Michael Steiner

Selected Publications Burey S. C. et al. 2007. Acclimation to lowCO2 by an inorganic carbon concentra-ting mechanism in Cyanophora parado-xa. Plant Cell Envir. 30:1422-1435.

Wunder T. et al. 2007. The invariantphenylalanine of precursor proteinsdiscloses the importance of Omp85for protein translocation into cyanel-les. BMC Evolutionary Biology 7:236.

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Stomatin associates with lipid droplets. Stomatin-GFP expressingMDCK cells were treated with oleic acid, fixed and stained withNile red. Large lipid droplets (red) are surrounded by stomatin-GFP(green).

Current model of cardio-myogenesis: During gastru-lation mesoderm gives riseto committed cardioblastswhich differentiate to adultcardiomyocytes. Somemesodermal cells escapedifferentiation and remainas cardiac stem cells in theheart, which eventually giverise to progenitor cells andcardiomyocytes.

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Our group investigates the structure and function of stomatinand SLP-1, two integral proteins that are anchored at thecytoplasmic side of cellular membranes via a hydrophobicdomain and palmitoylation. Stomatin is a ubiquitously expres-sed, oligomeric, cholesterol-binding, lipid raft-associated pro-tein that is thought to act as an integral coat protein likecaveolin-1. It associates with ion channels and the glucosetransporter Glut1 and regulates their activities in a choleste-rol-dependent manner. SLP-1 is highly expressed in brain. It

forms oligomeric complexes with stomatin in cholesterol-rich microdomains. Due to a sterol carrierSCP2-domain, SLP-1 is thought to act as a membrane-bound lipid transfer protein. Currently, we arestudying the function of stomatin/SLP-1/cholesterol complexes in endo- and exocytosis and [email protected]

Molecular cell biology and structure of the lipid raft proteinsstomatin and stomatin-like protein 1 (SLP-1)

RainerProhaska

TeamAnna-Maria Husa

Herbert Jank Ulrich Salzer

Selected Publications Umlauf E. et al. 2006. Characterizationof the stomatin domain involved inhomo-oligomerization and lipid raftassociation. J Biol Chem. 281:23349-23356.

Salzer U. et al. 2007. Stomatin: A newparadigm of membrane organizationemerges. Dynamic Cell Biology 1:20-33.

Cardiomyogenesis is induced by a plethora of morphogenssecreted by tissues of all three germ layers during early gast-rulation and regulated by several mesodermal and cardiacspecific transcriptions factors. We are interested in the mole-cular mechanisms involved in regulatory networks guidingcardiomyogenesis and defined the growth factor SPARC, thecytoskeletal protein desmin and the transcription factorNkx2.5 as components of a new network regulating cardio-myogenesis both in the primitive mesoderm of embryoid

bodies and in cardiac stem and progenitor cells clonally isolated from murine hearts. These aspectscontribute to the generation of cardiomyocytes from embryonic and somatic stem cells as a modelfor cardiomyogenesis and as a future source for a sustainable cell therapy of the [email protected]

Signal transduction in specification and differentiation of cardiac progenitor cells

GeorgWeitzer

TeamArlind Ardili

Harmen Auner Sonja Gawlas

Scheinast Matthias Mark Wiedner

Selected Publications Hofner M. et al. 2007. Desmin stimula-tes differentiation of cardiomyocytesand upregulation of brachyury andnkx2.5. Differentiation 75:605-615.

Höllrigl A. et al. 2007. Cardiomyocytesrequires functional serine residues wit-hin the amino-terminal domain of des-min. Differentiation 75:616-626.

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Model for endoplasmic reticulum-associated degradation (ERAD): Enzymes,lectins and molecular chaperones work as folding factors on nascent

(glyco)proteins in the lumen of the ER. After retrotranslocation of ERAD substra-te proteins through a proteinaceous channel from the ER to the cytosol, their

degradation occurs via the ubiquitin proteasome pathway.

Foreword

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Project LeaderIn the endoplasmic reticulum (ER) a quality control system operates thatensures that only properly folded proteins will be released. Misfoldedpolypeptides are retro-translocated from the ER to the cytosol, andthere become poly-ubiquitinated and destructed by proteasomes. ER-associated degradation (ERAD) is of relevance for a variety of geneti-cally inherited, neurodegenerative, and virally transmitted diseases withprotein folding defects. We are interested in the molecular characteri-zation of the multi-step ERAD process, and attempt to elucidate requi-rements of the substrate (glyco)proteins and to detect factors involved.Moreover, in joint projects with Marcela Hermann and Wolfgang J.Schneider (MFPL), we study protein quality control also in the contextof the biosynthesis of lipoproteins and [email protected]

N. Erwin Ivessa

TeamRobert Hermann Matthias Spork

Selected Publication Kitzmüller C. et al. 2003. Processing ofN-linked glycans during endoplasmic-reticulum-associated degradation of ashort-lived variant of ribophorin I.Biochem. J. 376:687-696.

Synthesis, folding, transport, and degradation of proteins in the early secretory pathway

The virus φCh1 was found by spontaneous lysis of a culture of the halo-alkaliphilic, archaeon, Natrialba magadii, an isolate from the sodalake, Lake Magadii in Kenya. This organism has an optimal growth at3.5M NaCl and at a pH of 9.5. The virus itself is used as a modelsystem to analyse gene expression in haloalkaliphilic organisms, facingwith two extremes: a high pH and high concentrations of salt. Currentlythe work concentrates on the identification and function of repressorand activator molecules encoded by the virus, gene regulation due toa recombination event, identification of the receptor for the virus on thecell surface of Nab. magadii and the transformation /shuttle vectorsystem developed by the [email protected]

Angela Witte

TeamChristian DerntlFlora HaiderAngela LadurnerChristina MeissnerMichael Reiter

Selected Publications Rössler N. et al. 2004. Inversion withinthe haloalkaliphilic virus phi Ch1 DNAresults in differential expression ofstructural proteins. Mol. Microbiol.52:413-426.

Iro M. et al. 2007. The lysogenic regionof virus phi Ch1: identification of arepressor-operator system and deter-mination of its activity in halophilicArchaea. Extremoph. 11:383-396.

φCh1, a model system for gene regulation of haloalkaliphilicArchaea facing two extremes: high pH and salt

We are interested in the structural basis of the respective catalytic pro-perties of monofunctional (typical) catalases and bifunctional catalase-peroxidases from various sources. Our main focus is on the organiza-tion of the active sites and the substrate channels leading to them.Recently we could show that in typical catalases structural fluctuationsin the wall of the narrow part of the major substrate channel control theaccess of different substrate species. We also study the presumptivefunction of inorganic ions as so-called “internal donors“ to prevent autoxidation of the enzyme. Additionally weattempt the preparation of catalases of increased structural stability by site-directed mutagenesis, including the intro-duction of inter-chain disulfide [email protected]

Franz Koller

TeamMohsen M. Farhadi

Selected Publication Zamocky M. et al. 2004. Expression,purification, and sequence analysis ofcatalase-1 from the soil bacteriumComamonas terrigena N3H. ProteinExpres. Purif. 36:115-123.

Structure-function studies of hydroperoxidases

Surface (in cyan) of the major channel leading to the active site of yeast catalase A.

Electron micrograph of a φCh1 particle negativly stained with uranyl acetate.

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Mitochondrial carnitine acyltransferases and L-carnitine traffic

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You dislike chemistry. That is not the fault of chemistry. It is also notyour fault. The reason might be that nobody explained it to you ina proper way – or that you did not read my books. Most peopleimagine chemistry as a kind of magic.Wrong. Every time you make photos or copies, when you paint orglue something, you do chemistry. And cooking is applied bio-chemistry anyway. The books describe the fundamental principlesof chemistry omitting bulky details, which makes it so bewildering

for the beginner. Details mayeasily be found in any encyclo-pedia or the internet, providedone has grasped the [email protected]

Chemistry for innocents

Edgar Wawra

Selected Publications Wawra E., Dolznig H. and Müllner E.2005, 3. Auflg. Chemie verstehen. Vlg.Facultas

Wawra E., Dolznig H. and Müllner E.2003, 1. Auflg. Chemie erleben. Vlg.Facultas

We study the transcriptional consequences of carnitine deficiency andsubsequent L-carnitine supplementation in human cells. Differences inmRNA expression levels and promoter active gene functions havebeen analysed by chip screen analysis, real time RT-PCR, reportergene and band shift assays. We have revealed that L-carnitine in addi-tion to its metabolic importance (ß-oxidation, acyl-CoAs) directly inter-acts with promoter active factors at specific sites, thus influencing awide spectrum of genes. Currently we are analysing L-carnitine indu-ced genes in more detail, focussing on transcription active factors. A second research project is tracing the effects associated with inhibi-tion of the macrophage colony-stimulating factor (CSF-1), when thisstrategy is used to inhibit growth of solid tumours and decrease the riskof metastasis. [email protected]

Signaling events after carnitine deficiency and CSF-1 inhibition

ReinholdHofbauer

TeamAshkan KhamenehBarbara Tappeiner

Our main interest is the elucidation of the molecular mechanisms of fer-tilization and germ cell maturation. Specifically, we have been study-ing the synthesis and assembly of the zona pellucida, an extracellularmatrix surrounding the oocyte, which also is the initial site of contactbetween sperm and egg. The components of the zona pellucida allbelong to the same protein family, the zp proteins. Recently, we havefocused on proteins that are structurally similar to the components ofthe zona pellucida and are expressed in the female follicle, but are notpart of the zona pellucida itself. In addition, we investigate the roles ofzp proteins in extraovarian [email protected]

Role of zona pellucida proteins

FranzWohlrab

Selected Publication Bausek N. et al. 2004. Interaction ofsperm with purified native chickenZP1 and ZPC proteins. Biol Reprod.71:684-690.

Avian liver tubuli are lined with the zonapellucida protein ZPAY

Selected Publication Godarova A. et al. 2005. L-Carnitineregulates mRNA expression levels ofthe carnitine acyltransferases CPT I,CPT II and CRAT. Chem. Monthly136:1349-1363.

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Crystal structure of the Sec2p/Sec4pcomplex – a catalytic coiled-coil in action

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My group is interested in understanding the molecularmechanisms of vesicular transport in eukaryotic cells.Vesicular transport is essential for sorting and deliveringnewly synthesized proteins from the endoplasmic reticulum(ER) through the Golgi to target compartments including thecilium and flagellum. Our goal is to elucidate the assemblymechanisms of the protein complexes that are responsiblefor cargo transport to and within the cilium. We mainly useX-ray crystallography to visualize these proteins and theircomplexes. Our structural studies will be complemented bysite-directed mutagenesis and in vitro/vivo experiments to test our mechanistic hypotheses. The avai-lable new structures will enhance our understanding of how these complexes function and providehints as to how their malfunction leads to human diseases. [email protected]

Gang Dong

TeamHongwen Zhou

Selected Publications Dong G. et al. 2007. A catalytic coiled-coil: structural insights into the activati-on of the Rab GTPase Sec4p by Sec2p.Mol. Cell 25:455-462.

Dong G. et al. 2005. Structures ofExo70p and the Exo84p C-terminaldomains reveal a common motif. Nat.Struct. Mol. Biol. 12:1094-1100.

Structural studies of protein complexes for vesicular transport in eukaryotic cells

Junior Group Leaders

The creation of the MFPL was accompanied by a commitment from bothUniversities to fund 10 junior tenure-track positions over the next five years.With generous start-up packages and internationally competitive salaries, thefirst call went out in the autumn of 2007, and resulted in more than 100 excel-lent applications, 80% from foreign countries. From these, three accepted ouroffer of positions: Gang Dong, a crystallographer from Yale; Kristin Tessmar,from EMBL, who studies biological rhythms in bristle worms; and FlorianRaible, also from EMBL, who studies gene complexity during evolution. Weare delighted that they will make the MFPL their first scientific home as inde-pendent group leaders and we look forward to helping their progress in theyears to come.

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The polychaete Platynereis dumerilii (A) adult animal, (B) larvaat 2dpf (picture from H. Hausen) (C) The phases of the moon(top) control and synchronize the number of sexually maturePlatynereis adults.

Shedding light on gene regulatory networks: (A) Genomic alignments between Platynereis and another anne-lid worm, Nereis, reveal candidate noncoding elements (NCE)that integrate regulatory information. “Ex“ indicates conservedcoding exons. (B) 1-day old larva expressing EGFP from an inte-grated enhancer construct in the prototroch (pt, asterisk) and api-cal tuft (at, arrowhead), reflecting the activity of the regulatory ele-ment used in the injection construct.

We use a mixture of bioinformatic and experimentalapproaches to study the evolution of complexity in animaldevelopment. Experimentally, we study Platynereis dumerilii,an annelid worm and newly emerging model species thatexhibits a unique combination of ancestral-type genomiccharacteristics (Raible et al., Science 2005).As a main focus, we characterize the genes and gene-regu-latory networks implied in the development of thePlatynereis hormonal cell types and organs to understandtheir function and reconstruct the evolution of related celltypes in other animal taxa. Moreover, we are interested in

the global comparison of the Platynereis genome with those of other animals to discriminate bet-ween ancestral genomic features and more complex genetic novelties that arose in the respective

evolutionary [email protected]

Evolution of genomic and regulatory complexity

Florian Raible

TeamBenjamin Backfisch

Claudia Lohs

Our group is interested in inner brain sensory-neurosecreto-ry cells that are part of the ancient core of animal brains. Inorder to understand the function and evolutionary divergen-ce of these enigmatic cells, the lab follows a comparativeapproach using both zebrafish and the marine bristle wormPlatynereis. Besides the molecular analysis of the cells, we are inter-ested in their impact on biological rhythms. As in manyother marine animals, the spawning of Platynereis is syn-chronized by the moon. We can mimic this rhythm in the lab

culture, and use various molecular approaches to understand (a) the reception of the moonlight,(b)the transmission of the signal to the gonads and (c) the integration of lunar and circadian clocksignals in [email protected]

Lunar periodicity and the function of inner brain sensory-neurosecretory cells

KristinTessmar

TeamClaudia Lohs

Juliane Zantke

Selected Publications Tessmar-Raible K. et al. 2007. Conservedsensory-neurosecretory cell types inannelid and fish forebrain: insights intohypothalamus evolution. Cell 129:1389-1400.

Tessmar-Raible K. 2007. The evolution ofneurosecretory centers in bilaterianforebrains: insights from protostomes.Semin. Cell Dev. Biol. 18:492-501.

Selected Publications Tessmar-Raible K. et al. 2007. Conservedsensory-neurosecretory cell types inannelid and fish forebrain: insights into hypothalamus evolution. Cell 129:1389:1400.

Denes A. S. et al. 2007. Molecular archi-tecture of annelid nerve cord supportscommon origin of nervous system centralization in bilateria. Cell 129:277-288.

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Service & Support

Administration

MFPL Buildings

MFPL Main Building:

2nd Floor Maria Bausback, Regina Klaus, Helga Wieltschnig

3rd Floor Aini Kyynäräinen-Rennert, Thomas Lenert, Gabriele Waidringer, Sabina Winter, Nikola Wiskocil

4th Floor Günther Leitgeb, Angela Martins, Sabine Tschanter

5th Floor Gerlinde Aschauer, Erna Huber

6th Floor Lisa Cichocki, Renate Fauland, Stefan Götzinger,Thomas Grubmayr, Barbara Hamilton, Barbara Miksch, Jan Müller

Other Campus Buildings:

VBC2 Katharina Haberler, Karin Pfeiffer, Rita Stadler

VBC3 Natasa Peric

VBC5 Ursula Thalhammer

Staff Scientists & Technicians

MFPL Buildings

MFPL Main Building:

2nd Floor Sharif Duale, Ingrid Mudrak, Harald Rumpler, Thomas Sauer

3rd Floor Kornel Barta, Barbara Bublava, Romana Finsterberger, Irene Gösler, Martina Gschirtz, Katarzyna Biadasiewicz, Matthias Scheinast, Andrea Triendl, Günther Tschabuschnig, Karin Habegger, Diethelm Gauster

4th Floor Andrej Belokurov, Matthias Hamerl, Mirjana Iliev, Monika Kastler, Birgit Rapp, Theresa Sorger-Domenigg, Jochen Stadler, Ursula Stix

4th Floor Roman Bayer, Christian Bernhart, Irmgard Fischer, Elisabeth Jursa, Waltraud Kutschera, Harald Nierlich, Silvia Tömö, Helga Waltenberger

8th Floor Maria Granilshikova

Other Campus Buildings:

VBC2 Christian Pflügl

VBC5 Werner König, Karin Ledolter, Julia Schindelar, Claudia Schreiner

Animal House – Cornelia Deimböck, Silvia Krammer, Jacques Malekani-Anaginsi, Tamara Torrecilla Lobos, Denise Vorauer

Biooptics: Light Microscopy & FACS – Josef Gotzmann, Edgar Wawra

Electron-Microscopy – Harald Kotisch, Siegfried Reipert, Bhuma Wysoudil

Green House – Sebastian Schwarz, Fatima Touraeva

Mass Spectrometry – Dorothea Anrather, Edina Czaszar, Ilse Dohnal, Sonja Frosch, Richard Imre, Sonja Kolar

Nuclear Magnetic Resonance – Georg Kontaxis

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Social Life

MFPL Social Activities”Work hard – play hard“ – this is the social motto of the MFPL members.Who knows what the scientists are talking about while they are relaxing? Maybe they stilldiscuss science or plan their next research collaboration? Who knows – maybe the next im-portant discovery is being prepared. …or they just sit together and enjoy a relaxed time withtheir colleagues.

MFPL Happy HourOnce a month one or two research groups organize the MFPL Happy Hour – a get-togetherfor all MFPL members with food and drinks – and open end. For each Happy Hour the stu-dents create their own motto – we already saw ”Hawaiian Surf Style“, attendance strictly inSurfing clothes only, ”Crisscross“, wearing your clothes inside out, ”Carnival Happy Hours“with a ”best costume award“, Christmas and Easter Happy Hours according to the time ofthe year, Karaoke Singing, Oktoberfest and certainly many more will follow…

MFPL Sports activities: ”Running Experiments“MFPL students and staff are active in various sports throughout the year: ONE Dragon Boat Cupin spring, Wien Energie Business Run in summer, MFPL Ski Trip in winter and VBC Volleyball /Basketball training group throughout the year.

No matter if Vienna City Marathon or Werthner's Everyman Decathlon – MFPL members showtheir versatility and team spirit when it comes to participating in all kind of sporting activities –competitive ambitions or just for having fun – come and join our sports team!

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Research Funding

Dr. Bohr-G

asse

Viehmarktgasse

Landstrasser Hauptstr.

Land

stras

ser H

aupt

stras

se

Rennweg

Entrance

Railway Statio

n

S 7 (from/to

Airport)

Vienna Biocenter

St. Marx

18 Tram Stop

74 A Bus Stop (from City)

74 A Bus Stop (from City)

se

Land

stras

ser H

aupt

stras

se

74 B

us S

top

(to C

ity)

71 Tram Stop

to U3 Underground

Helmut-Q

ualtinger-G

asse

18 Tr

am S

top

Where to find MFPL:

The Max F. Perutz Laboratories want to thank the following institutions for financial support of research projects:AICR UK – Association for International Cancer Research, United Kingdom

BMWF – Austrian Ministry of Science and Research

GEN-AU – Genome Research Austria

Christian Doppler Society (CDG) – CDG Christian Doppler Society

DebRA

DFG – German Research Foundation

EMBO – European Molecular Biology Organization

EU – European Union

Eurasia Uninet Fellowship

FEBS – Federation of Biochemical Societies

FFG – Austrian Research Promotion Agency

FWF – Austrian Science Fund

Herzfelder Stiftung

Hochschuljubiläumsstiftung der Stadt Wien

Interreg IIIa

Johanna Mahlke geb. Obermann-Stiftung zur Förderung der Krebsforschung an der Uni Wien

Jubiläumsfond der Österreichischen Nationalbank

Medical University of Vienna

ÖAD – Austrian Exchange Service

ÖAW – Austrian Academy of Sciences

Theodor Körner Fonds

University of Vienna

Wings for Life Spinal Cord Research Foundation

WWTF – Vienna Science and Technology Fund

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enRü

c

Alphabetical Group Leader Index

Editor | Lisa Cichocki

Design | Grafikatelier Heuberger | Vienna

Photography | Lisa Cichocki | Arnd Oetting – Porträt Seite 31 | Group Leader Archive

Printing | Kärntner Druckerei | Klagenfurt

Dr. Lisa Cichocki | Communications

Max F. Perutz Laboratories | Dr. Bohr -Gasse 9 | A -1030 Wien

T: +43 -1-4277-24014 | F: +43-1-4277-9240

E: [email protected] | W: http://mfpl.ac.at Lisa Cichocki

Imprint

Ammerer Gustav

Baccarini Manuela

Bachmair Andreas

Barta Andrea

Blaas Dieter

Bläsi Udo

Brocard Cécile

Charpentier Emmanuelle

Decker Thomas

Djinovic Carugo Kristina

Dong Gang

Dorner Silke

Foisner Roland

Gregan Juraj

Hartig Andreas

Heberle-Bors Erwin

Hermann Marcela

Hermisson Joachim

Hirt Heribert

Hofbauer Reinhold

Ivessa N.-Erwin

Jantsch Michael

Jantsch-Plunger Verena

Klein Franz

Koller Franz

Konrat Robert

Kovarik Pavel

Köhler Gottfried

Kragler Friedrich

Kuchler Karl

Loidl Josef

Lorkovic J. Zdravko

Löffelhardt Wolfgang

Meskiene Irute

Moll Isabella

Müllner Ernst

Nimpf Johannes

Ogris Egon

Pichler Andrea

Pittner Fritz

Poppenberger Brigitte

Prohaska Rainer

Propst Friedrich

Raible Florian

Rotheneder Johann

Schlögelhofer Peter

Schneider Wolfgang

Schroeder Renée

Schüller Christoph

Schweyen Rudolf

Seipelt Joachim

Seiser Christian

Sieberer Tobias

Skern Tim

Teige Markus

Tessmar Kristin

Touraev Alisher

Von Haeseler Arndt

Waigmann Elisabeth

Warren Graham

Wawra Edgar

Weitzer Georg

Wiche Gerhard

Witte Angela

Wohlrab Franz

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Annual Report 2007

Contact | Max F. Perutz LaboratoriesDr. Bohr-Gasse 9 | 1030 Vienna | AustriaPhone | [email protected] | www.mfpl.ac.at

MFPL are a joint venture of:

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