The Institute of Medical Genetics/Max-Planck Institute for Molecular genetics combines expertise in the molecular genetics of Marfan syndrome (including investigations on recombinant proteins and mouse models), clinical medical genetics, computational biology, and the biology of the TGF-beta/BMP superfamily.

Facilities description: patient recruitment, animal facilities, proteomic technologies, different microscopic analytic tools, semiautomatic in situ hybridization, human cell culture laboratory, and a bioinformatics workgroup are available in our workgroup.

Tasks in FAD:

Bioinformatic prioritization of candidate disease genes, recruitment and phenotyping of patients for new gene discovery and characterization of modifying genes, large scale in situ hybridization analysis of aortic samples of genetically modified mice, investigation of effects of fibrillin/elastin fragmentation in mouse models. Investigation of osteogenic response of vascular smooth muscle cells to elastin/fibrillin fragments and characterization of altered signalling pathways.

Members of the FAD staff

 Robinson, PN (MD, MSc), Medical Genetics, Molecular Genetics, Animal Models, Computational Biology, WP2, WP3
 Seemann, P (PhD) Molecular genetics, disease gene identification, cell culture models, animal models, WP2, WP3

Main publication/patent linked to FAD tasks

 Guo G, Booms P, Halushka M, Dietz HC, Ney A, Stricker S, Hecht J, Mundlos S, Robinson PN (2006) Induction of macrophage chemotaxis by aortic extracts of the mgR Marfan mouse model and a GxxPG-containing fibrillin-1 fragment. Circulation. 114:1855-62. Booms P, Ney A, Barthel F, Moroy G, Counsell D, Gille C, Guo G, Pregla R, - Mundlos S, Alix AJ, Robinson PN. (2006) A fibrillin-1-fragment containing the elastin-binding-protein GxxPG consensus sequence upregulates matrix metalloproteinase-1: biochemical and computational analysis. J Mol Cell Cardiol. 40:234-46.
 Booms P, Pregla R, Ney A, Barthel F, Reinhardt DP, Pletschacher A, Mundlos S, Robinson PN. (2005) RGD-containing fibrillin-1 fragments upregulate matrix metalloproteinase expression in cell culture: a potential factor in the pathogenesis of the Marfan syndrome. Hum Genet. 116:51-61.
 Seemann P, Schwappacher R, Kjaer KW, Krakow D, Lehmann K, Dawson K, Stricker S, Pohl J, Ploger F, Staub E, Nickel J, Sebald W, Knaus P, Mundlos S (2005) Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2. J Clin Invest. 115:2373-81.
 Booms P, Tiecke F, Rosenberg T, Hagemeier C, Robinson PN. (2000) Differential effect of FBN1 mutations on in vitro proteolysis of recombinant fibrillin-1 fragments. Hum Genet. 107:216-24.