Plasticity of clathrin-mediated endocytosis in development

发育过程中网格蛋白介导的内吞作用的可塑性

• 批准号: 2282992
• 金额: --
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2282992
• 关键词: Plasticity; clathrin; mediated; endocytosis; development

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.

细胞表面蛋白水平是组织完整性和细胞间通讯的关键，在发育过程中，蛋白质水平会根据发育组织的需要迅速调整。例如，在组织伸长过程中，快速移除细胞表面的细胞粘附分子对于细胞重排至关重要，而在重排完成后，粘附分子需要存在以允许正确的图案。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。网格蛋白介导的内吞作用（CME）是去除细胞表面蛋白的主要途径，许多CME的分子参与者已经从培养细胞的工作中被阐明。然而，培养细胞不受发育信号如信号和机械力的影响，因此不适合理解这些信号如何调节CME。在这个项目中，我们的目标是了解CME在体内的可塑性。最先进的遗传、成像和计算技术的结合将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定量发育和细胞生物学的培训，并掌握光遗传学，超分辨率显微镜和自动图像分析的技能。