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How do we make sperm, eggs, and embryos with the appropriate number of chromosomes?
How do we make sperm, eggs, and embryos with the appropriate number of chromosomes?
During meiosis, chromosomes must be accurately segregated to create gametes (sperm and eggs) with 1/2 the parental genome, so that fertilization restores proper chromosome number in the resulting embryo. One process critical to successful chromosome segregation is crossover formation, a type of DNA repair that physically exchanges chromosome arms and creates a temporary connection between chromosome pairs. I like to think of this connection like folding a pair of socks together so they don't become separated in your chaotic sock drawer; crossover-based connections keep homologous chromosomes together in a chaotic cellular environment prior to segregation in the first meiotic division. Failure to form crossovers can lead to the production of gametes with the incorrect number of chromosomes, a leading cause of infertility, miscarriage, and congenital birth defects.
The microscopic roundworm C. elegans is an excellent model system to study meiosis.
1) Key meiotic factors and processes are conserved between C. elegans and humans, enabling discoveries in worms to inform our understanding of human health and reproduction.
2) The events of meiosis can be observed by immunofluorescence staining (see diagram) or by live imaging of the worm's germ line. Important to our work, C. elegans is extremely proficient at regulating and ensuring meiotic crossover formation: Orderly chromosome segregation relies on the successful maturation of just a single crossover-designated site per chromosome pair!
3) C. elegans is highly amenable to genetic manipulation and biochemical approaches, providing a powerful system to test hypothesis regarding meiotic mechanisms.
Research projects in our lab aim to understand:
Research projects in our lab aim to understand:
What regions of crossover-promoting proteins are important for crossover formation?
Do morphological and biophysical properties of crossover complexes reflect underlying DNA repair state?
How does the ordered assembly and timing of crossover factor interaction govern crossover maturation?
Can we drive assembly of crossover-site-like compartments and stimulate crossover repair?
What mechanisms promote and ensure reliable crossover formation?
What mechanisms promote and ensure reliable crossover formation?
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