Gene expression in programmed cell death

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，在发育过程中，当手指之间的细胞通过程序性细胞死亡而死亡时，手指就会形成。贝尔实验室已经发现并继续领导对一种新的细胞程序性死亡途径的研究，该途径被称为TAF6Delta途径。TAF6Delta途径在几个重要方面与已知的细胞死亡途径不同。这些包括它在缺乏中心自杀蛋白P53的情况下杀死细胞的能力，更重要的是，编码TAF6的基因对细胞生存是必不可少的，而其他已知的细胞死亡蛋白的基因则不是。在这里，我们提出了一个研究计划，以TAF6通路为模型，更好地了解细胞如何能够解释其环境，以决定是自杀还是继续生存。我们建议回答三个研究问题。1)首先，我们知道TAF6在细胞死亡过程中被细胞酶切割。我们将询问这种分裂是否能够加速或潜在地减缓细胞死亡过程。2)其次，我们将剖析负责启动TAF6Delta途径的分子。我们将使用一种名为质谱学的强大分析技术来识别控制TAF6Delta表达的细胞蛋白质。3)第三，我们将使用实验和计算方法确定TAF6 Delta在体内的表达位置。*我们的研究结果将进一步阐明TAF6 Delta途径及其对细胞死亡的影响。更好地了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，包括阿尔茨海默病和癌症等神经退行性疾病，都是由于细胞死亡失控造成的。此外，细胞死亡的控制在生态学、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，我们的研究计划为培养下一代年轻科学家提供了一个多学科、包容和协作的环境。通过提供对编程细胞的更深入的见解，并通过为年轻研究人员创造培训机会，我们的研究计划将为充满活力的加拿大知识型经济做出贡献。

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.**************