SFB 807: Transport and Communication across Biological Membrans

生物膜与生命的进化密切相关，它提供了细胞内外的屏障，允许区隔化、结构形成以及分子的集中。然而，任何活细胞都必须通过这一屏障与其环境进行交流，因此，膜上配备了大量的膜蛋白，这些膜蛋白是分子摄取和输出以及跨越这一屏障进行交流（感知刺激和信号转导到细胞内目标）所必需的。膜蛋白的这一关键作用在所有生命领域的基因组中都得到了例证，其中25- 30%的遗传信息编码膜蛋白。尽管膜蛋白对细胞生理很重要，但对膜蛋白及其过程的精确理解却很少。特别是，运输过程和信息传递往往没有很好地解决，尽管从生物医学的角度来看，它们是最重要的，这反映在目前使用的大约60%的医疗药物靶向跨膜过程这一事实。我们的知识和跨膜过程的重要性之间的差异将确保这一研究领域在未来几年将成为学术研究和制药行业的焦点。该合作研究中心旨在通过综合多学科方法，研究不同细胞系统和亚细胞区室中分子和信息跨膜运输的原理和分子机制。该联盟结合了大量的生物化学、生物物理学、细胞和结构生物学以及计算方法来阐明这些过程的分子细节。这就需要确定一个转移周期中关键事件的时间顺序、它们的时间尺度和结构基础。特别是，假设转运体和受体具有完成完整活性周期所需的多种构象的能力，需要识别这些基本构象状态并了解它们之间如何发生交换。我们将通过分析这些事件与其他膜蛋白以及细胞内和细胞外因子的串扰来解决这些事件如何整合到大分子复合物和信号网络中。

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.