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

基于膜的蛋白质支架是典型的动态、亚稳态结构，它形成了基于亲和力的多组分基质。SFB 958的研究表明，它们在时空上受控的组装和拆解在膜运输和重塑、细胞信号转导以及分化和发育中发挥着至关重要的作用。SFB 958中的多学科结合方法已经并将导致识别和提取动态组织的蛋白质-蛋白质组合支架细胞膜的通用分子机制。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“使能”技术，例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在分子定义良好的细胞环境中分析膜支架所得出的一般原理是否能够解释并可能预测更高水平的生物功能。我们认识到，理论建模对于彻底了解支架机制越来越重要。为了加强这一领域，我们邀请了来自以色列特拉维夫大学的世界领先的理论家Michael Kozlov加入该联盟，他开创了用理论生物物理方法研究膜/蛋白质系综动力学的先河。此外，冷冻电子显微镜的最新进展反映在由冷冻电子显微镜领军人物克里斯蒂安·斯潘领导的新Z05项目中。最后，我们已将另外两个由新招聘的初级教师Francesca Bottanelli和David Owald领导的项目纳入该财团。财团结构的这些变化，以及在前几个资金时期在SFB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细说明的雄心勃勃的目标，从而使我们对正在研究的支架有更精细的分子理解。

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.