Grant: Project Grant

Meiosis is the specialized form of the cell cycle by which diploid cells produce the haploid gametes required for sexual reproduction. Defects in meiosis have profound consequences for human health. It is estimated that more than half of pregnancy loss and congenital birth defects result from errors during meiosis. Studies in yeast and mice have shown that metal ions such as zinc and copper are essential for normal progression of meiosis. Insufficient levels of these metal ions lead to meiotic arrests as well as errors during meiosis. Despite the known essential role for copper during meiotic differentiation, copper-dependent regulators and copper transport proteins involved in this developmental process remain poorly understood. Germ cells are present in a very small number in most mammals, making molecular studies that require substantial amounts of material a formidable task. An additional problem comes from the fact that both animal models and tissue co-culture cells are extremely difficult to synchronize with respect to their entry into meiosis. Our research model is based on the unique biology of the yeast Schizosaccharomyces pombe. In this organism, meiosis can be induced in a highly synchronous manner, thereby allowing meiotic steps to be monitored and dissected directly. This unique property makes S. pombe particularly useful in the elucidation of basic principles that govern meiosis. Moreover, as several proteins identified in copper metabolism and copper transport in yeast have human homologs, developing a complete understanding of this process in yeast will have a direct impact on the identification of meiotic genes important in human reproduction. The goal of this research is to provide a better understanding of key mechanistic aspects of copper-related proteins that are required for faithful and healthy reproduction (fertility) and to understand how aberrations can lead to meiosis-related diseases such as infertility and gametogenic defects.