Molecular mechanisms regulating cell fate

调控细胞命运的分子机制

• 批准号: 402152-2011
• 负责人: Christian, Sherri
• 金额: $ 2.55万
• 依托单位: Memorial University of Newfoundland
• 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=550799
• 关键词: Molecular; mechanisms; regulating; cell; fate

Cells interact with their environment through proteins at the cell surface, known as receptors. Through a domino effect, the activation of these receptors causes activation of a series of proteins inside in the cell. This series of proteins is known as a signalling pathway. These pathways then instruct the cell how to respond to its environment. By activating these pathways, a cell can be instructed to, among other consequences, divide, develop, or die. Sometimes activation of the same pathway can result in drastically different consequences depending on the cell type or other environmental signals. It is not clear how activation of the same pathway can result in different consequences for the cell, or cell fates. The Christian lab is interested in understanding the mechanisms that direct different cell fates even when common proteins, receptors or pathways are activated. To begin this work, we will focus on a model system where one receptor, known as CD24, causes very different effects depending on the cell type. Cells that are destined to become antibody-producing cells, known as B cells, will die if CD24 is activated. In contrast, in some cancer cells CD24 instructs the cell to survive. Our goal is to identify the mechanisms that determine if a specific cell will live or die in response to CD24. These studies will significantly improve our understanding of how cells decide if they will live or die. Furthermore, the characterization of these mechanisms may identify proteins that could be targeted to alter the ability of a cell to live or die.

细胞通过细胞表面的蛋白质（称为受体）与环境相互作用。通过多米诺骨牌效应，这些受体的激活导致细胞内一系列蛋白质的激活。这一系列蛋白质被称为信号通路。然后，这些通路指示细胞如何对其环境做出反应。通过激活这些通路，细胞可以被指示分裂、发育或死亡。有时，相同途径的激活可能会导致完全不同的结果，这取决于细胞类型或其他环境信号。目前尚不清楚相同途径的激活如何导致细胞或细胞命运的不同后果。Christian实验室有兴趣了解指导不同细胞命运的机制，即使在常见蛋白质，受体或途径被激活时。为了开始这项工作，我们将集中在一个模型系统，其中一个受体，称为CD24，导致非常不同的影响，这取决于细胞类型。如果CD24被激活，注定要成为抗体产生细胞的细胞，即B细胞，就会死亡。相反，在一些癌细胞中，CD24指示细胞存活。我们的目标是确定决定特定细胞是否会响应CD24而存活或死亡的机制。这些研究将大大提高我们对细胞如何决定它们是活还是死的理解。此外，对这些机制的表征可以鉴定出可以靶向改变细胞生存或死亡能力的蛋白质。