SFB 958: Scaffolding of Membranes: Molecular Mechanisms and Cellular Functions

基于膜的蛋白质支架通常是动态的、亚稳态的结构，它形成了一个基于亲和度的多组分基质。SFB 958的研究表明，它们的时空控制的组装和拆卸在膜运输和重塑、细胞信号传导以及分化和发育中起着至关重要的作用。在SFB 958中结合多学科方法已经并将导致鉴定和提取通用的分子机制，通过这些机制，动态组织的蛋白质-蛋白质组合支撑细胞膜。这使得我们对它们如何发挥其细胞功能，从而发挥机体功能的理解有所提高。在SFB 958中，我们研究了一系列生物实体和动态过程中的支架，从细胞信号和感觉转导到细胞内运输和机械转导。SFB 958的研究人员已经实施了新的和尖端的“启用”技术，如各种形式的超分辨率光学显微镜，冷冻电子断层扫描和多种生理分析。对这种复杂生物系统的研究将使我们能够评估从分子定义良好的基于细胞的环境中膜支架分析得出的一般原理是否可以解释并可能预测更高水平的生物功能。我们认识到，理论建模是越来越重要的脚手架机制的透彻理解。为了加强这一领域，我们邀请了来自特拉维夫大学（以色列）的世界领先理论家迈克尔·科兹洛夫（Michael Kozlov）加入该联盟，他率先通过理论生物物理方法研究膜/蛋白质系综动力学。此外，低温电子显微镜的最新进展反映在由著名低温电子显微镜专家Christian Spahn领导的新Z05项目上。最后，我们将新招募的初级教师Francesca Bottanelli和David Owald领导的另外两个项目纳入了联盟。联盟结构的这些变化，加上SFB在之前的资助期内收集的尖端技术和专业知识，将使我们能够实现申请中详述的雄心勃勃的目标，这将使我们对所研究的支架有更精确的分子理解。

Membrane-based protein scaffolds are typically dynamic, metastable structures, which form an avidity-based multicomponent matrix. Work by SFB 958 has revealed that their spatiotemporally controlled assembly and disassembly plays crucial roles in membrane traffic and remodeling, cell signaling, as well as in differentiation and development. The combined multidisciplinary approaches within SFB 958 have and will lead to the identification and extraction of generic molecular mechanisms by which dynamically organized protein-protein assemblies scaffold cellular membranes. This results in an improvement of our understanding of how they exert their cellular and, consequently, organismal functions.Within SFB 958, we investigate scaffolds across a spectrum of biological entities and dynamic processes, ranging from cell signaling and sensory transduction to intracellular transport and mechano-transduction. Researchers of SFB 958 have implemented new and cutting-edge “enabling” techniques, such as various forms of super-resolution light microscopy, cryo-electron tomography and multiple physiological assays. The study of such complex biological systems will allow us to assess whether the general principles derived from the analysis of membrane scaffolds in molecularly well-defined cell-based settings can explain and, possibly, predict biological function at higher levels. We recognize that theoretical modeling is of increasing importance for a thorough understanding of scaffolding mechanisms. To strengthen this area of we have included Michael Kozlov, a world-leading theoretician from Tel Aviv University (Israel), who has pioneered the study of membrane/protein ensemble dynamics by theoretical biophysical approaches, in to the consortium. Moreover, the recent progress in cryo-electron microscopy is reflected by the new Z05 project led by Christian Spahn, a leading cryo-electron microscopist. Lastly, we have included two additional projects led by newly recruited junior faculty Francesca Bottanelli and David Owald into the consortium.These changes in the structure of the consortium together with the cutting-edge technologies and expertise gathered within the SFB during the previous funding periods will enable us to achieve the ambitious goals detailed in the application that will lead to a refined molecular understanding of the scaffolds under study.