The Role of the RasGTPase Superfamily Signaling in C.elegans

RasGTPase 超家族信号传导在秀丽隐杆线虫中的作用

• 批准号: 342190-2013
• 负责人: Kubiseski, Terrance
• 金额: $ 2.19万
• 依托单位: York University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=572472
• 关键词: Role; RasGTPase; Superfamily; Signaling; C.elegans

The Ras-family of proteins plays crucial regulatory roles in biology by controlling cell growth and development. Inappropriate activity of this family of proteins is known to lead to human diseases and they play a fundamental role in cell biology. Although we have a good understanding of some simple functions of these proteins, some things we do not know are (i) how they are regulated, (ii) once they are switched on, what other proteins do they bind and (iii) how these proteins are altered to carry out their biological function. We propose to investigate these fundamental issues in cell biology by using C.elegans as a model organism. The "worm" has proven to be very useful for developmental and genetic studies because it is easy to grow, small enough for characterization of every individual cell in the organism (@1000 total cells) and we can manipulate it by safely adding modified genes. Worm genes involved in fundamental cell biological processes are very similar to human genes that have the same cellular function. Therefore, studying worm genes are useful to understanding how human genes work. Our work is focused on the Ras binding protein named BRAP-2. We have determined that mutations in the worm homolog of BRAP-2 cause the animals to show defects in its DNA damage response, which is an important process for maintaining genetic stability and viability of an organism. We plan to carry out further genetic and biochemical studies to better understand how the worm's BRAP-2 regulates the DNA damage rResponse, and discover other genes and proteins BRAP-2 interacts with to fulfill its function.

Ras蛋白家族通过控制细胞生长和发育在生物学中起着至关重要的调节作用。 已知该蛋白质家族的不适当活性会导致人类疾病，并且它们在细胞生物学中起着重要作用。 虽然我们对这些蛋白质的一些简单功能有了很好的了解，但我们不知道的是：（i）它们是如何被调节的;（ii）一旦它们被打开，它们会结合哪些其他蛋白质;（iii）这些蛋白质是如何被改变以实现其生物学功能的。 我们建议以秀丽隐杆线虫为模式生物来研究细胞生物学中的这些基本问题。 “蠕虫”已被证明对发育和遗传研究非常有用，因为它很容易生长，小到足以表征生物体中的每个细胞（@1000个总细胞），我们可以通过安全地添加修饰基因来操纵它。 蠕虫基因参与基本的细胞生物学过程，与人类基因非常相似，具有相同的细胞功能。 因此，研究蠕虫基因有助于了解人类基因是如何工作的。 我们的工作集中在Ras结合蛋白BRAP-2上。 我们已经确定BRAP-2的蠕虫同源物中的突变导致动物在其DNA损伤反应中显示出缺陷，这是维持生物体遗传稳定性和生存力的重要过程。 我们计划进行进一步的遗传和生化研究，以更好地了解蠕虫的BRAP-2如何调节DNA损伤rResponse，并发现BRAP-2与其他基因和蛋白质相互作用以实现其功能。