University of Cologne 

Cells are complex and dynamic structures whose properties must be adjusted to specific needs defined by physiological conditions or developmental programmes. The diversity and plasticity of cellular systems is brought about by a surprisingly limited number of genes and gene products and therefore cannot simply be explained by the activity of individual proteins in a cell. The SFB 635 has taken an interdisciplinary approach to investigate posttranslational control mechanisms. It brings together research groups employing genetic, cell biological, biochemical and structure biological methods in evolutionarily diverse model organisms, including eubacteria, yeast, Drosophila, Arabidopsis and mice. The collaborative approach promotes the rapid recognition of conserved principles in regulation and, perhaps even more importantly, variations thereof as adjustment to specific demands. Research within the SFB 635 centres around three regulatory principles which determine protein function: 1) the covalent modification of proteins, 2) dynamic protein assemblies, and 3) the regulated degradation of proteins. This promotes an integrative view of control mechanisms which is out of reach for individual research projects. At the same time, the high degree of synergy in methodology and technical experience promotes quality and success in research projects within the SFB. This promotes an integrative view of control mechanisms which is out of reach for individual research projects.

Work within research area A during previous funding periods showed that specific modifications, such as phosphorylation, ubiquitylation, or lipidation, can regulate the activity as well as the subcellular localisation of proteins in a variety of ways. With crystal structures of key players becoming available, several projects succeeded now to elucidate on a structural level how the modification of a protein affects its function.

Projects within research area B analyse how protein-protein interactions regulate activities and functional specificities of proteins. These interactions can be dynamic or lead to the formation of stable multiprotein complexes and often are regulated by covalent modifications. Projects within area B are therefore intimately linked to research areas A and C within the SFB 635.

Projects within research area C investigate the regulation of cellular functions by protein degradation. Proteolysis offers the possibility to rapidly and irreversibly adjust cellular activities. Proteins can be activated or inhibited by specific processing events or their stability and abundance is regulated.