Grant: Project Grant

Human reproduction requires the fusion of egg and sperm that each contains exactly half the number of parental chromosomes to form a healthy embryo containing a complete chromosome set. Inheriting an abnormal number of chromosomes is the most prevalent and documented cause of miscarriage, and is also associated with sterility and developmental defects. To produce egg and sperm, germ cells go through two specialized rounds of cell division called meiosis. Correct distribution of the parental chromosomes to these cells relies on meiotic processes which pair identical chromosomes along their lengths and physically anchor them to each other through DNA "crossovers" in preparation for segregation; failure to form crossovers results in germ cells containing abnormal chromosome numbers. While the events leading to crossover formation are highly conserved from fungi to humans, the study of meiotic processes in humans is difficult because of technical and ethical issues. In our laboratory, we use C. elegans, a small transparent roundworm that possesses many of the genetic counterparts found in vertebrates to study meiosis. Using the powerful genetic, molecular and biochemical tools of the nematode system, combined with the accessibility of the germline for detailed microscopy, we propose to identify and study new genes required for the critical processes regulating crossing over with the goal of understanding meiosis in humans.