Research Report 2010 - MDC

Genetics and Pathophysiology of Cardiovascular DiseasesStructure of the GroupNikolaus RajewskyGroup LeaderProf. Dr. Nikolaus RajewskyScientistsCatherine AdamidiDr Kevin ChenDr Minnie FangGraduate StudentsMarc FriedlaenderMarvin JensAzra Krek*Svetlana LebedevaJonas MaaskolaSebastian Mackowiak*Systems Biology of Gene RegulatoryElementsMy lab uses experimental (molecular biology, biochemistry) together with computationalmethods (bioinformatics, computational biology, etc) to dissect, systems-wide, functionand evolution of gene regulation in metazoans. One major focus is to understand moreabout post transcriptional gene regulation exerted by small RNAs, in particular microRNAs.We are developing predictive models for targets of microRNAs. We also investigate generalmechanisms of gene regulation by microRNAs and RNA binding proteins in cell lines and invivo. For example, we are studying the function of small RNAs during early development inC. elegans (Fig. 1). Furthermore, we have established planaria (Fig. 2) as a model system in ourlab. These freshwater flatworms are famous for their almost unlimited ability to regenerateany tissue via pluripotent, adult stem cells. We investigate the role of small RNAs inplanarian stem cell biology and regeneration.IntroductionA major lesson from recent genomics is that metazoansshare to a large degree the same repertoire of proteinencodinggenes. It is thought that differences betweencells within a species, between species, or betweenhealthy and diseased animals are in many cases due todifferences in when, where and how genes are turnedon or off. Gene regulatory information is to a largedegree hardwired into the non-coding parts of thegenome. Our lab focuses on decoding transcriptionalregulation (identification and characterization of targetsof transcription factors in non-coding DNA) andpost-transcriptional control mediated by small, noncodingRNAs, in particular microRNAs. microRNAs are arecently discovered large class of regulatory genes, presentin virtually all metazoans. They have been shown tobind to specific cis-regulatory sites in 3’ untranslatedregions (3’ UTRs) of protein-encoding mRNAs and, byunknown mechanisms, to repress protein production oftheir target mRNAs. Our understanding of the biologicalfunction of animal microRNAs is just beginning toemerge, but it is clear that microRNAs are regulating orinvolved in a large variety of biological processes andhuman diseases, such as developmental timing, differentiation,long-term memory, signaling, homeostasis ofkey metabolic gene products such as cholesterol, apoptosis,onset of cancer, Tourette’s syndrome, and others.Overall, however, it is clear that miRNAs are only a smallpart of the entire post transcriptional gene regulationapparatus used by cells, and we are beginning to alsoexplore the role of RNA binding proteins.Systems Biology of Gene RegulationCatherine Adamidi, Kevin Chen, Minnie Fang, MarcFriedlaender, Signe Knespel, Azra Krek, AndreasKuntzagk, Svetlana Lebedeva, Jonas Maaskola, MarlonStoeckius, Nadine Thierfelder26 Cardiovascular and Metabolic Disease Research