About Our Research

Meiosis is the fascinating process by which sexually reproducing organisms generate haploid gametes. A hallmark of meiosis is DNA recombination, which generates genetic diversity and ensures accurate chromosome segregation. While we have gained insights on the molecular determinants of meiotic recombination initiation in mammals, the processes leading up to it remain largely unexplored. A round of DNA replication precedes meiotic cell division but technical challenges have precluded its study in mammals. As a result we have limited understanding of the interplay between replication and recombination. We have developed techniques to generate high-resolution maps of meiotic recombination initiation in individual human genomes, and a robust approach to track replication origins and replication timing during meiosis. Having established a correlation between replication and recombination, we will now apply these methods to identify the proteins involved in this link and examine how disrupted replication affects recombination, genome stability and fertility. In addition, we will determine the 3D chromatin structure of human meiotic chromosomes to identify its role on modulating meiotic replication, recombination and germline mutagenesis. Successful completion of these projects will provide the needed mechanistic insight to design therapeutic intervention to prevent infertility, miscarriages, and birth defects.