Molecular, cellular, and developmental mechanisms of septin disease alleles

项目总结/摘要 细胞功能和组织完整性依赖于细胞形状和组织的维持。细胞骨架， 含有聚合物和马达蛋白，除了促进细胞的生长外， 组织结构septins是一个保守的形成细胞骨架的家族， 蛋白质支架和隔蛋白失调可促进许多人类疾病。本提案的目的是 了解septins如何通过使用septin促进细胞和组织的行为和组织 人类疾病中的等位基因我将结合联合收割机高分辨率成像，细胞生物学，分子生物学， 发育生物学、基因组编辑和生物物理学，以实现上述目标。我的工作将由 通过三个目的：（1）研究临床septin突变和缺失如何影响组织， 功能;（2）阐明septin突变如何干扰胞质分裂;（3）定义septin突变如何影响 聚合和高阶结构功能。建议的实验将建立使用C。 elegans作为一种体内系统，以克服目前围绕septin研究的局限性， septin功能障碍如何在人类疾病期间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.