Molecular, cellular, and developmental mechanisms of septin disease alleles

项目摘要/摘要 细胞的功能和组织的完整性有赖于维持细胞的形状和组织。细胞骨架， 含有聚合物和马达蛋白，除了促进细胞结构和重塑细胞外 组织架构。一个保守的细丝形成家族，Septins，通过作为 蛋白质支架和Septin失调可能会导致许多人类疾病。这项提议的目标是 了解Septin如何通过Septin的使用对细胞和组织的行为和组织做出贡献 在人类疾病中发现的等位基因。我将结合高分辨率成像，细胞生物学，分子生物学， 发展生物学、基因组编辑和生物物理学，以实现上述目标。我的工作将被指导 通过三个目标：(1)研究临床Septin突变和缺失如何影响组织结构和 功能；(2)阐明Septin突变如何扰乱细胞质分裂；(3)定义Septin突变如何影响 聚合和高阶结构的作用。拟议的实验将确定C。 ELEGAN作为体内系统来克服目前围绕Septin研究的局限性，并将提供洞察力 研究在人类疾病期间，隔膜蛋白功能障碍如何扰乱细胞和组织的组织和功能。

PROJECT SUMMARY/ABSTRACT Cell function and tissue integrity rely on the maintenance of cell shape and organization. The cytoskeleton, containing polymers and motor proteins, serves to structure and remodel the cell in addition to facilitating tissue architecture. A conserved filament-forming family, the septins, influences the cytoskeleton by serving as a protein scaffold and septin dysregulation may promote many human diseases. The goal of this proposal is to understand how septins contribute to cell and tissue behavior and organization through the use of septin alleles found in human disease. I will combine high-resolution imaging, cell biology, molecular biology, developmental biology, genome editing, and biophysics to achieve the forestated goal. My work will be directed by three aims: (1) Investigate how clinical septin mutations and depletion affect tissue organization and function; (2) Elucidate how septin mutations perturb cytokinesis; (3) Define how septin mutation affects polymerization and higher-order structure function. The proposed experiments will establish the use of C. elegans as an in vivo system to overcome current limitations surrounding septin study and will provide insight into how septin dysfunction can perturb cell and tissue organization and function during human disease.