Cytoskeletal regulation during c. elegans embryogenesis

c. 细胞骨架调节

• 批准号: 371363-2009
• 负责人: Piekny, Alisa
• 金额: $ 2.7万
• 依托单位: Concordia University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=550035
• 关键词: Cytoskeletal; regulation; during; c.; elegans

We will investigate how the cytoskeleton mediates cell shape changes, a process that is fundamental for the development of eukaryotes. The cytoskeleton is composed of filamentous networks of proteins such as actin, myosin and tubulin that provide the architecture of the cell and are carefully regulated to mediate cell shape changes. If cells fail to change shape during development, this failure could prevent proper tissue formation, which would be disastrous for the organism. In addition, cancer cells also undergo shape changes for metastases and tumour progression, by a mechanism similar to cells during development. Recent studies in cell division revealed a role for anillin as a global scaffold and regulator of the cytoskeleton. However most of these studies were done on cells in culture and it is not known if anillin regulates additional contractile events that are relevant within the context of a tissue. I hypothesize that anillin modulates cytoskeletal dynamics to mediate cell shape changes during embryonic development by a mechanism similar to cell division. To test this hypothesis, I will use a combination of molecular, genetic and biochemical techniques using C. elegans embryogenesis as a model to investigate the regulation of cytoskeletal dynamics by anillin in vivo. These studies will be of general interest to the public given the fundamental roles that the cytoskeleton has for development and cancer progression.

我们将研究细胞骨架如何介导细胞形状的变化，这一过程是真核生物发展的基础。细胞骨架由肌动蛋白、肌凝蛋白和微管蛋白等蛋白质的丝状网络组成，它们提供细胞的结构，并被精心调节以介导细胞形状的变化。如果细胞在发育过程中不能改变形状，这种失败可能会阻止正常的组织形成，这对生物体来说将是灾难性的。此外，癌细胞在转移和肿瘤进展过程中也会发生形状变化，其机制与细胞在发育过程中类似。最近的细胞分裂研究揭示了氨苄素作为细胞骨架的整体支架和调节剂的作用。然而，这些研究大多是在培养细胞上进行的，尚不清楚苯胺素是否调节了组织内相关的额外收缩事件。我推测，在胚胎发育过程中，苯胺素通过类似于细胞分裂的机制调节细胞骨架动力学，从而介导细胞形状的变化。为了验证这一假设，我将采用分子、遗传和生化技术相结合的方法，以秀丽隐杆线虫的胚胎发生为模型，在体内研究氨苄素对细胞骨架动力学的调节。鉴于细胞骨架在癌症发展和进展中的基本作用，这些研究将引起公众的普遍兴趣。