Florencia Pratto, Ph.D., Stadtman Tenure-Track Investigator, NIH Distinguished Scholar

Current Research

Gametes, such as sperm and eggs, are produced through meiosis. In this specialized type of cell division, a single round of DNA replication is followed by two successive rounds of chromosome segregation. In the first division, homologs (each parental chromosome) separate; in the second division, the sister chromatids segregate, resulting in four haploid daughter cells. The segregation of homologs poses a unique challenge because they must be physically connected for accurate segregation. The connection between homologs, in most mammals, is mediated by the deliberate introduction of hundreds of double-stranded breaks (DSBs) and their subsequent repair through homologous recombination. The cell needs to fine-tune the timing and placement of DSBs to avoid deleterious events, such as mutations or aneuploidies. 20% to 60% of human oocytes have a karyotypic defect, and errors in meiosis are responsible for at least half of clinically recognized miscarriages, as well as a spectrum of chromosomal birth defects in humans, such as Down syndrome.

The main focus of our research is to understand the multiple layers that shape the recombination landscape over size scales ranging from single nucleotides to whole chromosomes in the human and mouse germlines. To achieve this goal we use a combination of genetics, multi-omics analysis and microscopy. Successful meiosis requires the coordination of multiple cellular and molecular processes. Through this research program, I seek to advance our knowledge of a critical biological process at the core of modern genetics that profoundly affects human reproductive health and disease.

Research in Plain Language

During the process of meiosis, which is how cells divide to form gametes (eggs and sperm), there is a step where genetic material is exchanged between chromosomes. This exchange, called recombination, shuffles the genetic information and creates new combinations of genes. Meiotic recombination plays a key role in creating genetic diversity while ensuring genomic stability. This genetic diversity is crucial for the evolution and adaptation of species over time. It provides a way for new traits and combinations of genes to arise, which can be beneficial for the survival of populations in changing environments. We strive to understand how this process is controlled and anticipate errors that are linked to infertility and aneuploid conditions such as Down’s Syndrome.