Plasticity of clathrin-mediated endocytosis in development

细胞表面蛋白质水平对组织的完整性和细胞间的交流至关重要，在发育过程中，蛋白质水平会根据发育组织的需要进行快速调整。例如，在组织伸长过程中，快速从细胞表面移除细胞-细胞黏附分子对于细胞重排至关重要，而在重排完成后需要黏附分子存在，以允许正确的图案形成。这意味着必须有复杂的系统来微调细胞表面的蛋白质水平。氯化蛋白介导的内吞作用(CME)是去除细胞表面蛋白的主要途径，在培养细胞中的许多分子作用已经被阐明。然而，培养中的细胞不受信号和机械力等塑造有机体的发育线索的影响，因此不适合理解这些线索是如何调节CME的。在这个项目中，我们旨在了解CME在体内的可塑性。最先进的遗传学、成像和计算技术的结合将被应用于作为模式生物的果蝇和哺乳动物细胞。成功的候选人将接受数量发育和细胞生物学方面的培训，并获得光遗传学、超分辨率显微镜和自动图像分析方面的技能。

Levels of cell surface proteins are key for tissue integrity and cell-cellcommunication and, during development, proteins levels are rapidly adjusted tothe needs of the developing tissue. For example, rapid removal of cell-celladhesion molecules from the cell surface is vital for cell rearrangement duringtissue elongation, while adhesion molecules need to be present afterrearrangements are completed to permit correct patterning. This means thatthere must be sophisticated systems to fine-tune levels of proteins at the cellsurface.Clathrin-mediated endocytosis (CME) is the principal pathway for the removal ofcell surface proteins and many of the molecular players in CME have beenelucidated from work in cultured cells. However, cells in culture are notsubjected to developmental cues such as signaling and mechanical forces,which shape an organism, and are therefore unsuitable for understanding of howthese cues regulate CME.In this project we aim to understand the plasticity of CME in vivo. A combinationof state-of-the-art genetic, imaging and computational techniques will be appliedin Drosophila, as a model organism, and mammalian cells. The successfulcandidate will be trained in quantitative developmental and cell biology andacquire skills in optogenetics, super-resolution microscopy and automatedimage analysis.