Mechanisms that induce and regulate gametogenic differentiation

诱导和调节配子分化的机制

• 批准号: 262070-2010
• 负责人: Stuart, David
• 金额: $ 1.97万
• 依托单位: University of Alberta
• 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=547972
• 关键词: Mechanisms; induce; regulate; gametogenic; differentiation

Research in my lab is focused on understanding how cells make the decision to grow and divide or to stop dividing and differentiate into specialized tissues such as the sperm and egg cells that are required for sexual reproduction. This process is very difficult to study in humans and so we use a model organism, the budding yeast. When deprived of nutrients yeast cells stop dividing and initiate a process similar to human sperm formation, however instead to sperm, spores are formed. To accomplish this process the cells must "turn off" many of the genes required for growth and cell division while they "turn on" entirely new sets of genes that encode proteins required for the transformation from proliferating cells into spores. We have discovered that the proteins controlling expression of meiosis-specific genes become modified by the addition of phosphate during the process of meiosis and spore formation and these modifications have a huge impact on their function. Proteins that repress the meiosis-specific genes become inactivated and a protein that induces the meiosis-specific genes becomes activated by this modification process. We have identified a meiosis-specific protein kinase (Ime2) that we suspect is responsible for phosphorylating the transcription factors that control the meiosis-specific genes. We are using a series of genetic biochemical methods to determine how phosphorylation influences the properties of the transcriptional activators and repressors that control the meiosis-specific genes. This research is aimed at understanding how one set of meiosis-specific genes is regulated. In particular we are focusing on how these genes are repressed during growth and what changes happen to the repressor to allow the activation of these genes during meiosis and sporulation. Through our investigations of yeast we have identified several proteins that perform essential functions for the spore formation process; several of these are very similar to human proteins that are required for gamete formation. This research program will increase our understanding of the basic biochemistry that regulates gene expression and will provide insight into the control of gamete formation that is requuired for sexual reproduction.

我实验室的研究重点是了解细胞如何决定生长和分裂或停止分裂并分化成特定组织，如有性生殖所需的精子和卵细胞。这个过程很难在人类身上进行研究，所以我们使用了一种模式生物，芽殖酵母。当缺乏营养时，酵母细胞停止分裂，并启动类似于人类精子形成的过程，但与精子不同的是，孢子形成。为了完成这一过程，细胞必须“关闭”生长和细胞分裂所需的许多基因，同时“打开”编码从增殖细胞转化为孢子所需蛋白质的全新基因组。我们已经发现，控制减数分裂特异性基因表达的蛋白质在减数分裂和孢子形成过程中被磷酸盐修饰，这些修饰对其功能产生巨大影响。抑制减数分裂特异性基因的蛋白质被灭活，诱导减数分裂特异性基因的蛋白质被该修饰过程激活。我们已经确定了减数分裂特异性蛋白激酶（Ime 2），我们怀疑是负责磷酸化的转录因子，控制减数分裂特异性基因。我们正在使用一系列的遗传生化方法来确定磷酸化如何影响控制减数分裂特异性基因的转录激活因子和抑制因子的特性。这项研究旨在了解一组减数分裂特异性基因是如何调控的。特别是，我们正在关注这些基因在生长过程中是如何被抑制的，以及在减数分裂和孢子形成过程中，阻遏物发生了什么变化，使这些基因被激活。通过我们对酵母的研究，我们已经确定了几种在孢子形成过程中发挥重要作用的蛋白质;其中几种与配子形成所需的人类蛋白质非常相似。这项研究计划将增加我们对调节基因表达的基本生物化学的理解，并将提供对有性生殖所需的配子形成控制的深入了解。