C.H.S.-Stiftung
zur Förderung biomedizinischer Forschung
PD Dr. Ingolf Bach
1993 Ph.D., Pasteur Institute, Paris, France
1993-1996 Post-doc, HHMI, UC San Diego, USA
1996-1998 Assistant Researcher, HHMI, UC San Diego, USA
1998-2005 Group Leader, ZMNH, Hamburg
Research: Neuronal Cell Fate Specification
The LIM domain mediates protein-protein interactions and is found in various proteins such as LIM homeodomain transcription factors (LIM-HD), LIM-only (LMO) proteins and LIM kinases (LIMK). LIM-HD proteins have been shown in numerous examples to specify cell lineages and to regulate neuronal differentiation and brain morphogenesis during the development of many species from C. elegans to humans. LMO proteins are oncoproteins, identified as causing human cancer, whereas LIMK regulates the dynamics of the actin cytoskeleton with important consequences for cell morphology, cell motility and the development of neuronal projections. Recent data indicate that LIM domain proteins are present in cells as complexes consisting of multiple proteins and that their biological activity is regulated by LIM domain-associated cofactors.
The research carried out in our laboratory seeks to identify the molecules and molecular mechanisms by which LIM domain protein complexes are regulated during mouse and zebrafish embryogenesis by applying molecular, biochemical and genetic methods. In our previous work we have identified the cofactors CLIM/Ldb/NLI and RLIM, which bind to nuclear LIM domains and critically regulate the biological activity of LIM-HD transcription factors. We have further shown that post-translational modifications such as ubiquitination play crucial roles in the regulation of protein complexes associated with nuclear and cytoplasmic LIM domains.
Selected Publications:
Bach, I. & Ostendorff, H.P. (2003). Orchestrating nuclear functions: ubiquitin sets the rhythm. Trends Biochem. Sci. 28, 189-195.
Becker, T., Ostendorff, H.P., Bossenz, M., Schlüter, A., Becker, C.G., Peirano, R.I. & Bach, I. (2002). Multiple functions of LIM domain-binding CLIM/NLI/Ldb cofactors during zebrafish embryogenesis. Mech. Dev. 117, 75-85.
Ostendorff, H.P., Peirano, R.I., Peters, M.A., Schlüter, A., Bossenz, M., Scheffner, M. & Bach, I. (2002). Ubiquitination-dependent cofactor exchange on LIM homeodomain transcription factors. Nature 416, 99-103.
Bach, I. (2000). The LIM domain: regulation by association. Mech. Dev. 91, 5-17.
Bach, I., Rodriguez-Esteban, C., Carrière, C., Bhushan, A., Krones, A., Rose, D.W., Glass, C.K., Andersen, B., Izpisúa Belmonte, J.C. & Rosenfeld, M.G. (1999). RLIM inhibits functional activity of LIM homeodomain transcription factors via recruitment of the histone deacetylase complex. Nat. Genet. 22, 394-399.
Bach, I., Carrière, C., Ostendorff, H.P., Andersen, B. & Rosenfeld, M.G. (1997). A family of LIM domain associated cofactors confers transcriptional synergism between LIM- and Otx homeodomain proteins. Genes Dev. 11: 1370-1380.
Bach, I., Rhodes, S.J., Pearse, R.V., Heinzel, T., Gloss, B., Scully, K.M., Sawchenko, P.E. & Rosenfeld, M.G. (1995). P-Lim, a LIM homeodomain factor, is expressed during pituitary organ and cell commitment and synergizes with Pit-1. Proc. Natl. Acad. Sci. USA 92: 2720-2724.