SFB 1177: Molecular and Functional Characterization of Selective Autophagy

选择性自噬是一种针对溶酶体降解的各种细胞成分的细胞内分解代谢过程。它对细胞内稳态至关重要，任何放松调控都有助于人类疾病的病理生理学，如癌症、神经退化和感染。这是德国在自噬领域的第一次协调一致的跨学科努力，因此获得了国际知名度。在过去的七年里，我们对自噬的分子基础及其调控、个体选择性自噬途径的功能以及自噬在人类疾病中的作用产生了详细的见解。此外，我们还为该领域的技术进步做出了贡献，今天法兰克福被公认为德国自噬研究的重要技术中心。对于第三个资助期，我们建议通过创建多学科研究团队来解决自噬中的几个具有挑战性的问题，从而使我们的研究达到高度综合和跨学科的水平。主要研究领域包括脂质和膜的重塑、细胞器周转的动力学、自噬在神经变性、免疫和炎症中的作用。自噬生物发生是该领域长期存在的难题之一，我们将研究货物性质、不同的磷脂和蛋白质对自噬生物发生的影响。在衰老和神经变性方面，我们的目标是阐明凝集物自噬降解的分子要求，并进一步加深我们对体内选择性自噬过程的动态调节的理解。我们还将进一步努力剖析自噬的抗菌功能。在免疫和炎症领域，我们将解决几个新出现的话题：选择性自噬和死亡信号在炎症组织损伤中的串扰，以及分泌型自噬在免疫动态平衡中的作用。最后，我们将研究自噬在造血中的作用。我们已经完成了几个项目，形成了翻译网络的关键种子。重要的是，我们在第三个资助期纳入了许多新的女性和年轻一代领导者。我们将重组我们的服务平台，以适应财团不断变化的需求：Z01平台将保持其定量蛋白质组学和分子动力学建模的活动，而Z02平台将以先进的成像和表型筛选技术为财团提供支持。CRC非常成功的教育计划将继续下去，包括综合研究和培训小组以及广泛关注的活动，如关于生命过程质量控制的法兰克福会议系列。

Selective autophagy is an intracellular catabolic process targeting various cellular components for lysosomal degradation. It is essential for cellular homeostasis and any deregulation contributes to pathophysiology of human diseases like cancer, neurodegeneration, and infections. This CRC has been the first concerted, interdisciplinary effort in the field of autophagy in Germany, and, as such, has gained international visibility. In the past seven years, we have generated detailed insights into the molecular basis of autophagy and its regulation, into functions of individual selective autophagy pathways, and the role of autophagy in human diseases. Additionally, we have contributed to advancing the field technologically, and today Frankfurt is recognized as an important technology hub for autophagy research in Germany. For the 3rd funding period, we propose bringing our research to high integrative and interdisciplinary levels by creating teams of multidisciplinary researchers that address several challenging questions in autophagy. Major areas of interest include lipid and membrane remodeling, dynamics of organelle turnover, the role of autophagy in neurodegeneration, in immunity, and inflammation. Autophagosome biogenesis is one of the longstanding conundrums in the field, and we will study how cargo properties, distinct phospholipids, and proteins influence it. With respect to aging and neurodegeneration, we aim to elucidate the molecular requirements for autophagic degradation of condensates, and further improve our understanding of the dynamic in vivo regulation of selective autophagy processes. We will also expand our efforts in dissecting the antibacterial functions of autophagy. In the field of immunity and inflammation, we will tackle several emerging topics: the crosstalk of selective autophagy and death signaling in inflammatory tissue damage, and the role of secretory autophagy in immune homeostasis. Finally, we will investigate the role of autophagy in hematopoiesis. We have completed several projects that formed a critical seed for translational networks Importantly, we have incorporated many new female and younger generation leaders in the 3rd funding period. We will restructure our service platforms to adapt to the changed needs of the consortium: Z01 platform will maintain its activities of quantitative proteomics and modeling of molecular dynamics, while Z02 platform will support the consortium with advanced imaging and phenotypic screening technologies. The highly successful education program of the CRC will be continued, encompassing both the Integrated Research and Training Group and widely visible events such as the Frankfurt Conference Series on Quality Control in Life Processes.