Generating distinct actin networks in a single cytoplasm: Structural studies to determine the impact of actin nucleators on filament structure

如果我们要在疾病状态的背景下进行相关和适当的干预，那么对细胞如何响应其环境的基本理解，以推动细胞生理学的变化至关重要。多年的研究表明，肌动蛋白细胞骨架是细胞调控的焦点，然而，我们对肌动蛋白丝形成的早期步骤的机制以及不同的丝组织如何在单个细胞质中共存的理解仍然存在很大的差距。本计画将结合联合收割机分子生物学与生物化学与先进的电子冷冻显微镜（CryoEM）方法，以获得肌动蛋白成核过程的新结构见解。它将得到世界一流的实验室的支持，这些实验室具有肌动蛋白生物化学和细胞生物学（Ayscough）以及使用CryoEM（Bullough）进行大分子复合物结构分析的专业知识。

A fundamental understanding of how a cell responds to its environment, in order to drive changes to cell physiology, is critical if we are to make relevant and appropriate interventions in the context of disease states. Many years of research have demonstrated that the actin cytoskeleton is a focal point of cell regulation, however there are still large gaps in our understanding of mechanisms governing early steps in actin filament formation and how distinct filament organizations can co-exist in a single cytoplasm. This project will combine molecular biology and biochemistry with advanced electron cryomicroscopy (CryoEM) approaches to gain new structural insights into the process of actin nucleation. It will be supported by world-class labs with expertise in actin biochemistry and cell biology (Ayscough) and in structural analysis of macromolecular complexes using CryoEM (Bullough).