Monica P. Colaiácovo
Professor of Genetics
We investigate the mechanisms underlying germline maintenance and accurate chromosome inheritance during meiosis. Addressing this is of vital importance in order to understand the sources of errors that result in infertility, miscarriages, birth defects such as Down syndrome, and tumorigenesis in humans. Our studies provide key insights into the molecular basis for the regulation of germline maintenance and meiotic chromosome segregation. Specifically, we apply combined genetic, molecular, cytological and biochemical approaches to:
- Understand the mechanisms promoting faithful meiotic chromosome inheritance at the molecular level and their regulation throughout meiotic progression.
- Explore meiotic chromosome dynamics and the roles of post-translational modifications in regulating chromosome synapsis, DNA double-strand break repair, and accurate chromosome segregation.
- Investigate the roles played by regulators of the chromatin landscape, such as histone methyltransferases and demethylases, in germline maintenance and DNA double-strand break repair.
- Identify the meiotic pathways affected by exposure to environmental toxicants and develop high-throughput screening strategies for the identification of novel environmental meiotic disruptors.
We are addressing these aims in the nematode C. elegans. This is an extremely amenable model system for studies of germ cell maintenance and meiosis, which shares a high degree of conservation with humans. The germline accounts for more than half of the cells in the adult worm and its nuclei are distributed throughout the gonad in a defined order, correlating with the sequential stages of classical meiosis. Super- and high-resolution 3D imaging of meiotic chromosomes can be carried out in the context of a well preserved nuclear architecture, pairing between homologs can be monitored by fluorescence in situ hybridization (FISH), and live imaging of lines expressing various fluorescently-tagged proteins allows for analysis of meiotic chromosome dynamics. Various approaches, including RNA-Seq, have led to the identification of meiotic gene candidates with germline-enriched expression in C. elegans. Techniques such as RNA-mediated interference (RNAi) and CRISPR-Cas9-guided genome editing allow for assessment of the function of germline-active genes. Analysis of protein interactions by IPs/MS analysis and yeast two-hybrid approaches complement studies of the post-translational modifications involved in regulating these protein functions. Our studies are therefore providing key insights into the molecular mechanisms regulating fertility and reproductive health, laying the foundation for the development of effective preventive strategies.
New Research Building, Room 334
77 Avenue Louis Pasteur
Boston, MA 02115