Mechanisms that induce and regulate gametogenic differentiation

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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.