Monica P. Colaiácovo
Professor of Genetics
We are investigating the mechanisms underlying germline maintenance and accurate meiotic chromosome segregation. Specifically, we are applying combined genetic, molecular, cytological and biochemical approaches to:
1) Understand the mechanisms promoting faithful meiotic chromosome inheritance at the molecular level and their regulation throughout meiotic progression.
2) Explore meiotic chromosome dynamics. In particular, the interplay between changes in chromosome configuration/structure during meiosis, and sister chromatid cohesion, homologous chromosome pairing, synapsis, and DNA double-strand break repair.
3) Investigate how the dynamic regulation of histone methylation and acetylation patterns affect germline maintenance and DNA double-strand break repair.
4) 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 Caenorhabditis elegans. This is an extremely amenable model system for studies of germ cell maintenance and meiosis. C. elegans 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. High-resolution 3-D imaging of meiotic chromosomes can be carried out in the context of a well preserved nuclear architecture, and pairing between homologs can be monitored by fluorescence in situ hybridization (FISH). Microarray technology applied to the C. elegans genome has led to the identification of meiotic gene candidates with germline-enriched expression. Techniques such as RNA-mediated interference (RNAi) and PCR-based screens for deletion alleles allow for assessment of the function of germline-active genes.
Addressing the aims outlined above is of vital importance in order to understand the sources of errors that result in dramatically deleterious outcomes including infertility, miscarriages, birth defects such as Down syndrome and tumorigenesis in humans. Our studies are therefore providing key insights into the molecular basis for the regulation of 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