Research Report 2010 - MDC

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Matthew PoyStructure of the GroupGroup LeaderDr. Matthew Poy*Graduate StudentsJiaxuan Chen*Maria Dolaptchieva*Dörte Matthäus*Sudhir Gopal Tattikota*microRNAs and Mechanisms ofMetabolic DiseasesType II diabetes has finally become recognized as a major challenge to global health. It isimperative to improve our understanding of the molecular mechanisms behind this disorderand develop new drug therapies. The pathophysiology of diabetes is undoubtedly complex,typically characterized by hyperglycemia resulting from varying states of insulin resistance andimpaired β-cell function. Oftentimes, the failure to regulate circulating blood glucose levels is aconsequence of the inability to produce sufficient amounts of insulin by the pancreatic β-cells.In our group, we focus on fundamental pathways regulating glucose metabolism and howaltered pancreatic islet physiology contributes to metabolic disorders such as type 2 diabetes.The mechanisms governing gene expression patternsintegrate both transcriptional activation, post-transcriptionalgene silencing, and post-translational modifications.In the last decade the complex picture of generegulation has been extended by the discovery ofmicroRNAs. MicroRNAs are short, approximately 22nucleotide long non-coding RNAs which are thought tobe involved in a number of evolutionary conserved regulatorypathways. Many published reports have clearlyillustrated a role for individual microRNA sequences indevelopmental timing, apoptosis, proliferation, differentiation,and organ development. However, in light ofthe many advances in the fields of microRNAs and RNAinterference, many questions remain concerning thefunctional role of microRNAs in tissues like the pancreaticislet. Our work aims to test the hypothesis thatmicroRNAs expressed in the islet play an important rolein the development and function of pancreatic β-cellsthrough their ability to regulate gene expression. Manydirect targets of microRNAs expressed in the pancreaticislet have never been studied with respect to β-cellbiology and it is important to understand how theycontribute to islet function. Using newly developedmouse models, a molecular understanding of the exactnature of microRNAs is necessary to develop therapeuticstrategies for the treatment of metabolic diseaseslike diabetes.Selected PublicationsPoy, MN, Hausser, J, Trajkovski, M, Braun, M, Collins, S, Rorsman, P, Zavolan,M and Stoffel, M. (2009). miR-375 maintains normal pancreatic α- andβ-cell mass. Proc. Natl. Acad. Sci. USA. 106(14):5813-8.Yi, R, Poy, MN, Stoffel, M, and Fuchs, E. (2008) A skin microRNA promotesdifferentiation by repressing ‘stemness’. Nature. 452(7184):225-29.Wolfrum, C, Poy, MN, and Stoffel, M. (2005) Apolipoprotein M is requiredfor pre-HDL formation, cholesterol efflux to HDL and protects againstatherosclerosis. Nature Med. 11, 418-422.Krek, A*, Grun, D*, Poy, MN*, Wolf, R, Rosenberg, L, Epstein, EJ,MacMenamin, P, da Piedade, I, Gunsalus, KC, Stoffel, M, Rajewsky, N. (2005)Combinatorial microRNA target predictions. Nat. Genet. 37(5):495-500.(* equal contribution)Poy, MN, Eliasson, L, Krützfeldt, J, Kuwajima, S, Ma, X, MacDonald, PE,Pfeffer, S, Tuschl, T, Rajewsky, N, Rorsman, P and Stoffel, M. (2004) Apancreatic islet-specific microRNA regulates insulin secretion. Nature.432(7014):226-30.58 Cardiovascular and Metabolic Disease <strong>Research</strong>
Technical AssistantAndrea Katzer** Start of the group: August 2008Decreased β-cell mass in miR-375KO pancreatic islets. Representativesections of pancreas from 10-week-old a)wild type and b)miR-375KOmice visualized by immunofluorescence after staining with insulin(green) and glucagon (red). Bar represents 25µm.Cardiovascular and Metabolic Disease <strong>Research</strong> 59
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Research Report 2010MAX DELBRÜCK C
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ContentInhaltContentInhalt.........
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Surgical OncologyPeter M. Schlag...
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at the MDC. The role of the institu
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in discovering genes that contribut
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The ECRC offers research space and
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etween disciplines such as biology,
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approaches from bioinformatics/syst
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von Humboldt Foundation (AvH). The
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organization to a larger, multi-fac
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Cardiovascular and Metabolic Diseas
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electrical signals. More recent wor
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Basic Cardiovascular FunctionStruct
Page 34 and 35: Figure 2: SORLA and sortilin in neu
Page 36 and 37: Annette Hammes(Delbrück Fellow)Str
Page 38 and 39: Ingo L. MoranoStructure of the Grou
Page 40 and 41: Figure 3. Membrane resealing assay
Page 42 and 43: Michael GotthardtStructure of the G
Page 44 and 45: Structure of the GroupSalim Seyfrie
Page 46 and 47: Structure of the GroupFerdinand le
Page 48 and 49: Francesca M. SpagnoliStructure of t
Page 50 and 51: Structure of the GroupKai M. Schmid
Page 52 and 53: Genetics and Pathophysiology of Car
Page 54 and 55: Figure 2. Planariato experimentally
Page 56 and 57: Norbert HübnerStructure of the Gro
Page 58 and 59: Structure of the GroupGroup LeaderF
Page 60 and 61: Figure 2. Omega-3 fatty acids prote
Page 62 and 63: Structure of the GroupDominik N. M
Page 64 and 65: Rainer DietzStructure of the GroupG
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Page 72 and 73: Structure of the GroupThoralf Niend
Page 74 and 75: Michael BaderStructure of the Group
Page 76 and 77: Natriuretic peptide systemJens Butt
Page 78 and 79: Structure of the GroupZsuzsanna Izs
Page 80 and 81: Young-Ae LeeStructure of the GroupG
Page 82 and 83: Structure of the GroupMatthias Selb
Page 86 and 87: Jana WolfStructure of the GroupGrou
Page 88 and 89: Structure of the GroupGroup LeaderD
Page 91 and 92: Cancer Research ProgramKrebsforschu
Page 93 and 94: are responsible for the emergence o
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Page 97 and 98: lead to an aberrant constitutive ac
Page 99 and 100: How Notch- and TGFβ signaling casc
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Page 105 and 106: Graduate StudentsSeda Cöl ArslanCa
Page 107 and 108: investigation, as is the cause of c
Page 109 and 110: Graduate StudentsÖzlem Akilli Özt
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Page 117 and 118: Graduate StudentsRami Hamscho*Qingb
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Page 121 and 122: URE ∆/∆ mice regularly develope
Page 123 and 124: PD Dr. Wolfgang Walther (GroupLeade
Page 125 and 126: For the delivery of naked DNA into
Page 127 and 128: ACBDMyc and FoxO transcription fact
Page 129 and 130: Graduate StudentsKatrin BagolaHolge
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Graduate StudentsSarbani Bhattachar
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vesicle transport to the Golgi. Our
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acbFigure 1a: EHD2 is tubulatingpho
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KnowledgeProbabilitiesknownPossible
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Graduate and undergraduatestudentsU
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successive oncogenic mutations. We
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CXCR5 drives the development of ect
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Graduate and undergraduatestudentsW
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Graduate andUndergraduate StudentsM
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Angela MensenStefanie WittstockBjö
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deficient mice, both major effector
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ant of CD3 delta coding for a 45-me
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Robert KudernatschLi-Min LiuAna Mil
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Sebastian GüntherTechnical Assista
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Graduate StudentsJana RolffAnnika W
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with murine hepatocytes showed morp
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Function and Dysfunction of the Ner
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The Neuroscience Department also es
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the coming years, Björn Schröder
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mice. Further analysis of the funct
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Signaling Pathways and Mechanisms i
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Control Olig3 -/-ABFigure 2. Geneti
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Thomas J. JentschStructure of the G
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Figure 2. Cellular model for ionic
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Structure of the GroupGroup LeaderF
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paired-pulse facilitation, less dep
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Gary R. LewinStructure of the Group
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Model summarizing the three waves o
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Structure of the GroupInes Ibañez-
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Jochen C. MeierStructure of the Gro
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Björn Christian SchroederStructure
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Structure of the GroupJan Siemens(S
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Structure of the GroupGroup LeaderD
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Imaging of the Living BrainStructur
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Pathophysiological Mechanisms of Ne
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Figure 2. Iba1 positive microglia c
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Erich E. WankerStructure of the Gro
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Scientific-Technical StaffAnja Frit
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Structure of the GroupJan Bieschke(
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Berlin Institute of Medical Systems
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etes, metabolic diseases and neurod
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A number of MDC investigators have
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Technical AssistantsClaudia Langnic
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has become a standardized data flow
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Phylogeny of cellulase genes from P
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Experimental and Clinical Research
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his patients, and a basic research
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The ultrahigh field MR facility was
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Structure of the GroupSimone Spuler
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Ralph KettritzStructure of the Grou
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Structure of the GroupJeanette Schu
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Maik GollaschStructure of the Group
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Technology PlatformsComputational B
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projects/ard/] to detect repeats li
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Simulation of line-scan images of C
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Development of an MRM method for qu
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mobility or turnover of the underly
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Left: Inside view of a FACSAria2 (f
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Examples fort the use of EM methods
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Oviducts lined up in pre-implantati
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Academic Appointments 2008-2009Beru
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Buch which is part of the Excellenc
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“Bioinformatics in Quantitative B
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Delbrück FellowsDelbrück-Stipendi
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Yinth Andrea Bernal-Sierra, a PhD s
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Congresses and Scientific MeetingsK
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SeminarsSeminare2008Speaker Institu
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Speaker Institute TitleKiyoshi Mori
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2009Speaker Institute TitleDavid G.
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Speaker Institute TitleJuri Rappsil
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The Helmholtz AssociationDie Helmho
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The Berlin-Buch CampusDer Campus Be
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the MDC, the existing collaboration
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Prof. Dr. Gary R. LewinMDC Berlin-B
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Prof. Dr. Renato ParoCenter of Bios
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Staff CouncilThe Staff Council is i
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Type of Financing/Art der Finanzier
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Research Projects 2008-2009Forschun
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CIC-5 Regulation und Endocytose am
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MDCMAX-DELBRÜCK-CENTRUMFÜR MOLEKU
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Index 275Bröske, A. . . . . . . .
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Index 277Gross, V. . . . . . . . .
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Index 279Kur, E. . . . . . . . . .
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Index 281Piano, F. . . . . . . . .
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Index 283Smink, J. . . . . . . . .
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Campus MapCampusplanRobert-Rössle-
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How to find your way to the MDCDer
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Research Report 2010 - MDC

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