institute of experimental genetics (ieg)

The Institute of Experimental Genetics (IEG) has long-standing and leading expertise in phenotype driven generation of mouse models using chemical mutagenesis and sensitised screens [1, 2]. Large-scale mutagenesis projects are embedded in international initiatives to coordinate and support the functional analysis of all mammalian genes (EUCOMM). The German Mouse Clinic (GMC) at the IEG was established as an open platform for the systemic and standardised phenotyping of mouse lines as models for human diseases. The interdisciplinary institution is a collaboration of experts from the GSF together with research groups from the whole of Germany. Protocols for the analysis of over 320 parameters in 14 disease areas [3] have been developed herein. Within the EUMORPHIA consortium the IEG contributed to the development of standards for the description of phenotypes. The methods have been evaluated at multiple sites across Europe and made publicly available [4].

In particular, the IEG applied the integration of multiple level data for comparative analyses of transcriptomes, proteomes and metabolomes of mouse models [5] and for complex phenotype data from the GMC (e.g. osteogenesis imperfecta) [6, 7]. This integration of a vast amount of phenotype and genotype data, often addressed as “systems biology”, is a central issue for the understanding of diseases.

Using the Delta/Notch pathway as a semantic module, we have succeeded in developing algorithmic models to simulate important aspects of this signalling cascade [8], such as the cooperativity of transcription factor binding sites for the Hes7 oscillator and the quantitative simulation of gene expression in thousand of cells behaving in a similar way to presomitic cells [9, 10].

The research interests of the Molecular Endocrinology Group include regulation of cell proliferation and differentiation by steroids, steroid metabolism [11, 12], role of peroxisomes in sterol and steroid metabolism as well as the molecular basis of Zellweger syndrome and different types of cancers [13]. Furthermore, the group is involved in the development of methods for metabolite profiling [14] and enzyme specific inhibitors with therapeutic indications.

The Genome Analysis Center (GAC) provides a platform for the development and application of methods in genome, proteome and metabolome research. The GAC, as a technology platform, is open to all institutes of the Helmholtz Zentrum München.

The IEG is also a partner of EMMA (European Mouse Mutant Archive), a non-profit repository for the collection, archiving and distribution of mouse strains relevant to biomedical research. The director of the IEG heads the EMMA network.

Research activities of the IEG will be extended towards the systemic analysis of environmental phenotypes in mouse models, the in depth analysis of the metabolic and genetic bases of diabetes and bone/cartilage related disorders, and the in silico modelling of Notch signalling-related biological processes.

   [1]  Rubio-Aliaga I, et al.  (2007) Genetics 175, 1451-1463
   [2]  Hrabé de Angelis MH et al. (2000) Nat Genet 25, 444-447
   [3]  Gailus-Durner V et al. (2005) Nat Methods 2, 403-404
   [4]  Brown SD et al. (2005) Nat Genet 37, 1155
   [5]  Mijalski T et al. (2005) PNAS 102, 8621-8626
   [6]  Lisse T, et al. (PLoS Genet, in press)
   [7]  Bender A et al. (2007) [Epub ahead of print]
   [8]  Teppner I, et al. (2007) BMC Dev Biol 7, 68
   [9]  Tiedemann HB, et al. (2007) J Theor Biol 248, 120-129
 [10]  Zeiser S, et al. (2006) Theor Biol Med Model 3, 11-16
 [11]  Lukacik P, et al. (2007) Biochem J 402, 419-427
 [12]  Marijanovic Z, et al. (2003) Mol Endocrinol 17, 1715-1725
 [13]  van Grunsen EG et al. (1998) PNAS 95, 2128-2133
 [14]  Prehn C, et al. (2007) Enzymol and Mol Biol of Carbonyl Metabol 13, 277-283