Institut für Experimentelle Genetik, IEG
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Institute of Experimental Genetics Institute of Experimental Genetics Anfahrt zum Helmholtz Zentrum München Institut für Experimentelle Genetik, IEG Helmholtz Zentrum München Prof. Dr. Martin Hrabé de Angelis Lehrstuhl für Experimentelle Genetik, TUM PD Dr. Johannes Beckers Model for Human Disease Institute of Experimental Genetics Thematische Schwerpunkte 1. Diabetes 2. Knochen- / Knorpelerkrankungen 3. Modell der embryonalen Entwicklung (Fokus: Notch Signalweg) Blume-Jensen, P., Janknecht, R., and Hunter, T. (1998), Curr Biol 8, 779-82. Institute of Experimental Genetics Institute of Experimental Genetics Caused by a cryptic splice site in Col1a1 T. Lisse, M. Hrabé de Angelis, et al., PLOS Genetics 2008 BONE & CARTILAGE DISEASES Model for type II OI Bone phenotype: Mineralisation defect (Nature 423, pp320) (Nature 423, pp333) (Nature 423, pp346) (Cell 85, pp307) Patterning Growth Remodeling Immune system Polydactyly ALI3, ALI9, ALI12, ALI19, ALI37 Osteogenesis imperfecta AGA2, SMA4 Osteoporosis DXA1, DXA2 Syndactyly ALI6, ALI10, ALI27 Bone deformity Fractures BMC and BMD reduced Rheumatoid arthritis Psoriatic arthritis ALI5, ALI14, ALI18 Osteoarthritis Ankylosis ALI34 Institute of Experimental Genetics Institute of Experimental Genetics The Screens Bisphosphonate rescues bone phenotype but n o t lethality % peri-lethality T. Lisse, M. Hrabé de Angelis et al. PLOS Genetics in press weeks Nature Methods 2005, Nature Genetics 2005, 2008, 2009, Cell 2009... www.mouseclinic.de Institute of Experimental Genetics Institute of Experimental Genetics SYSTEMIC DISEASES Bone phenotype Mineralisation defect Bone deformity Fractures Beaded ribs Reduced bone mineral content & decreased bone mineral density Systemic effects Lung phenotype Heart phenotype Reduced fat mass & increased lean mass Metabolic alterations Institute of Experimental Genetics Institute of Experimental Genetics Gene–environment interactions in Type 2 Diabetes pathogenesis Experimental mouse models Genetic factors Environment Allow for detailed & accurate phenotyping due to • Environmental factors that can be tightly controlled • Genetic diversity can be reduced • No limitations in biosamples mtGPAT1 KO e.g. NONcNZO10/LtJ Dll1C413Y mutants e. g. mUCP1 TG Mouse models Nutrition challenge Obesity (e.g. diet-induced) Maternal factors (embryo transfer) Type 2 Diabetes Pancreatic β-cell dysfunction (impaired insulin secretion) Impaired insulin action What develops first ? Localisation of organ-specific defect. mtGPAT1 KO Pathophenotype closely mimicks human polygenic obesity-induced diabetes • Hyperglyceamia • Pancreatic islet atrophy • Liver steatosis • Increased serum insulin, leptin, TAG PPARα KO and many more Mice with mutations in particular genes to unravel their function in T2D pathogenesis Institute of Experimental Genetics Institute of Experimental Genetics Key Activities of IEG Was wir anbieten: Large-scale genomics approaches: • Mutant Production (Mouse) – Mutagenesis Screens • Archiving: German node of EMMA • Phenotypic Characterisation – German Mouse Clinic • Genomics, Transcriptomics and Proteomics • Data Aquisition and Interpretation • In silico Functional Genomics Institute of Experimental Genetics Blockpraktikum "Entwicklungsgenetik der Tiere“ 10 ECTS (mit IDG) Themes: - From Genes to Mouse Mutants and their Phenotype Analysis - Zebrafish Embryology Tierversuche/Tierschutz Establishment & Culture of Embryonic Stem Cells Gene Mutagenesis in Embryonic Stem Cells Generation of Knockout/Transgenic Mice Cryoconservation of germ cells and in vitro fertilisation In vivo Mutagenesis (ENU, Transposons) Zebrafish Embryology Zebrafish Embryology Phenotyping I: Histology Phenotyping II: Gene expression analysis Phenotyping III: German Mouse Clinic Phenotyping IV: Behavioural Analysis • Forschungspraktika: – Anmeldung zu jeder Zeit – Praktikumsdauer 6 Wochen, bis zu 10 CPs – Vortrag und Präsentation der Arbeit im Anschluss and Praktikum • Blockpraktikum: Entwicklungsgenetik der Tiere • Seminare, Journal Clubs (SS) • Vorlesungen: – Entwicklungsgenetik – Genomik • Master/Diplomarbeiten und Promotionen Institute of Experimental Genetics Vorlesung: Entwicklungsgenetik First week in the life of a mouse From the gastrula to midgestation Principles in development How to get "organized” “Up and down, Back and Belly, Left and Right": The question of positional information. lateral inhibition - watch your neighbour!” epithelial-mesenchymal transformation - The same story everywhere. How to pattern extremities The other side of life – aging Organogenesis: "Get in Shape": Making bones and muscle from somites. the ectoderm/neuroectoderm and its derivatives the endoderm and its derivatives Development of sensory systems: visual system, auditory system, smell, taste and touch General discussion, social and ethical issues Institute of Experimental Genetics Institut für Experimentelle Genetik, IEG Helmholtz Zentrum München Prof. Dr. Martin Hrabé de Angelis Lehrstuhl für Experimentelle Genetik, TUM PD Dr. Johannes Beckers [email protected]
