Mechanisms that induce and regulate gametogenic differentiation

我实验室的研究重点是了解细胞如何决定生长和分裂，或者停止分裂和分化为特定的组织，如精子和卵细胞，这是有性繁殖所必需的。这一过程很难在人类身上研究，所以我们使用了一种模式生物--发芽酵母。当缺乏营养时，酵母细胞停止分裂，开始一个类似于人类精子形成的过程，而不是精子，形成孢子。为了完成这一过程，细胞必须“关闭”许多生长和细胞分裂所需的基因，同时“打开”一组全新的基因，这些基因编码从增殖细胞到孢子转化所需的蛋白质。我们发现，在减数分裂和孢子形成过程中，控制减数分裂特异基因表达的蛋白质会被磷酸盐修饰，这些修饰对它们的功能有巨大的影响。抑制减数分裂特定基因的蛋白质被灭活，而诱导减数分裂特定基因的蛋白质通过这个修饰过程变得激活。我们已经确定了一个减数分裂特异的蛋白激酶(IME2)，我们怀疑它负责磷酸化控制减数分裂特异基因的转录因子。我们正在使用一系列遗传生化方法来确定磷酸化如何影响控制减数分裂特定基因的转录激活因子和抑制因子的性质。这项研究旨在了解一组减数分裂特异基因是如何调控的。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，以及在减数分裂和产孢子过程中，抑制子发生了什么变化来允许这些基因被激活。通过对酵母的研究，我们鉴定了几种在孢子形成过程中发挥重要功能的蛋白质；其中几种蛋白质与人类配子形成所需的蛋白质非常相似。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，并将为有性繁殖所需的配子形成的控制提供洞察力。

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.