SFB 807: Transport and Communication across Biological Membrans

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Biological membranes are intimately associated with the evolution of life, providing a barrier to or within the cell that allows for compartmentalisation and structure formation as well as concentration of molecules. However, any living cell has to communicate via this barrier with its environment and, therefore, membranes are equipped with a multitude of membrane proteins that are required for uptake and export of molecules and for communication across this barrier (sensing of stimuli and signal transduction to intracellular targets). This pivotal role of membrane proteins is exemplified in genomes from all kingdoms of life, in which 25-30 percent of the genetic information encodes for membrane proteins. Despite their importance for the physiology of cells, a precise understanding of membrane proteins and processes are only rarely available. In particular, transport processes and information transfer are often not well resolved, even though they are of paramount interest from a biomedical standpoint of view as reflected by the fact that roughly 60 percent of the currently used medical drugs target transmembrane processes. This discrepancy between our knowledge and the importance of transmembrane processes will ensure that this research area will stay in the focus both of academic research as well as the pharmaceutical industry for years to come. The Collaborative Research Centre is designed to be a comprehensive multidisciplinary approach to study the principles and molecular mechanisms of transport of molecules and information across membranes in different cellular systems and subcellular compartments. The consortium combines a large set of biochemical, biophysical, cell and structural biological as well as computational approaches to elucidate these processes in molecular detail. This entails the determination of the chronological order of key events during a transfer cycle, their timescales and their structural bases. In particular, the presumed ability of transporters and receptors to adopt multiple conformations, which are required for completion of a full activity cycle, requires the identification of these essential conformational states and an understanding of how interchange between them occurs. We will address how these events are integrated into macromolecular complexes and signalling networks by analysing their crosstalk with other membrane proteins as well as with intra- and extracellular factors.