Gene expression in programmed cell death

程序性细胞死亡中的基因表达

• 批准号: RGPIN-2019-06034
• 负责人: Bell, Brendan
• 金额: $ 3.64万
• 依托单位: Université de Sherbrooke
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=689955
• 关键词: Gene; expression; programmed; cell; death

The normal development and survival of animals require that some of their cells undergo a form of cellular suicide, termed programmed cell death. For example, during development, fingers are formed when the cells between the fingers die via programmed cell death. The Bell laboratory has discovered and continues to lead investigations into a new pathway of programmed cell death, termed the TAF6delta pathway. The TAF6delta pathway differs from known pathways of cell death in several important respects. These include its ability to kill cells in the absence of a central suicide protein known as p53, and, more importantly, the fact that the gene that encodes TAF6 is essential to cell survival, whereas those of other known cell death proteins are not.******Here, we propose a research program to better understand how cells are able to interpret their environment to decide whether to undergo suicide or continue to live, using the TAF6 pathway as a model. We propose to answer three research questions. 1) Firstly, we know TAF6 is cleaved by cellular enzymes during cell death. We will ask whether or not this cleavage functions to accelerate or potentially slow down the cell death process. 2) Secondly, we will dissect the molecular responsible for turning on the TAF6delta pathway. We will identify cellular proteins that control TAF6delta expression using a powerful analytical technique called mass spectrometry. 3) Thirdly, we will determine where in the body TAF6delta is expressed, using both experimental and computational methods.******The outcome of our research will be to shed further light on the TAF6delta pathway and its impact on cell death. Better understanding cell death pathways has far-reaching applications in biomedicine and biotechnology. Concretely, several disease states, including neurodegenerative disorders such as Alzheimer's disease and cancer, result from uncontrolled cell death. Moreover, the control of cell death has potential applications in ecology, agriculture and the food industry to increase or decrease biomass. Importantly, our research program provides a multidisciplinary, inclusive and collaborative environment for the training of the next generation of young scientists. By providing deeper insights into programmed cell, and by creating training opportunities for young researchers, our research program will contribute to a dynamic Canadian knowledge-based economy.**************

动物的正常发育和生存需要它们的一些细胞经历一种形式的细胞自杀，称为程序性细胞死亡。例如，在发育期间，当指状物之间的细胞经由程序性细胞死亡而死亡时，形成指状物。贝尔实验室发现并继续领导对程序性细胞死亡新途径的研究，称为TAF6 δ途径。TAF6 δ途径在几个重要方面不同于已知的细胞死亡途径。这些包括它在缺乏称为p53的中心自杀蛋白的情况下杀死细胞的能力，更重要的是，编码TAF6的基因对细胞存活至关重要，而其他已知的细胞死亡蛋白则不是。在这里，我们提出了一个研究计划，以更好地了解细胞如何能够解释他们的环境，以决定是否进行自杀或继续生活，使用TAF6通路作为模型。我们提出了三个研究问题。1)首先，我们知道TAF6在细胞死亡过程中被细胞酶切割。我们将询问这种切割是否起到加速或潜在地减缓细胞死亡过程的作用。2)其次，我们将剖析负责开启TAF6 δ通路的分子。我们将使用一种称为质谱的强大分析技术来鉴定控制TAF6 δ表达的细胞蛋白。3)第三，我们将使用实验和计算方法来确定TAF6 δ在体内的表达位置。我们的研究结果将进一步阐明TAF6 δ通路及其对细胞死亡的影响。更好地理解细胞死亡途径在生物医学和生物技术中具有深远的应用。具体地说，几种疾病状态，包括神经退行性疾病，如阿尔茨海默病和癌症，是由不受控制的细胞死亡引起的。此外，控制细胞死亡在生态学、农业和食品工业中具有增加或减少生物量的潜在应用。重要的是，我们的研究计划为下一代年轻科学家的培训提供了一个多学科，包容和协作的环境。通过提供更深入的见解编程细胞，并通过为年轻的研究人员创造培训机会，我们的研究计划将有助于一个充满活力的加拿大知识型经济。