Biological and Biomedical Science
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Monica Colaiácovo

Department of Genetics
Harvard Medical School
New Research Building, Room 334
77 Avenue Louis Pasteur
Boston, MA 02115
Tel: (617) 432-6543
Fax: (617) 432-7663
Email: mcolaiacovo@genetics.med.harvard.edu
Web Page: The Colaiácovo Lab Page
5 postdoctoral fellows, 1 graduate student

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. Particularly, the interplay between changes in chromosome configuration/structure during meiosis, and homologous chromosome pairing, synapsis, DNA double-strand break repair and accurate segregation.
  3. Investigate the roles played by histone demethylases in germline maintenance and DNA double-strand break repair.

     

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 germline maintenance and meiotic segregation, laying the foundation for the development of effective preventive strategies.

 

References:

  • Whetstine JR, Nottke A, Lan F, Huarte M, Smolikov S, Chen Z, Spooner E, Li E, Zhang G, Colaiácovo M and Y Shi. (2006) Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell 125: 467-481.
  • Smolikov S, Eizinger A, Hurlburt A, Rogers E, Villeneuve AM and MP Colaiácovo. (2007) Synapsis-defective mutants reveal a correlation between chromosome conformation and the mode of double-strand break repair during Caenorhabditis elegans meiosis. Genetics 176: 2027-2033.
  • Smolikov S, Schild-Prufert K and MP Colaiácovo. (2008) CRA-1 uncovers a double-strand break-dependent pathway promoting the assembly of central region proteins on chromosome axes during C. elegans meiosis. PLoS Genetics 4(6): e1000088.
  • de Carvalho CE, Zaaijer S, Smolikov S, Gu Y, Schumacher J and MP Colaiácovo. (2008) LAB-1 antagonizes the Aurora B kinase in C. elegans. Genes & Development 22: 2869-2885.