Overview
Inheritance of a complete set of chromosomes is critical for fertility and production of viable offspring. However, all chromosomes are not the same. Cells face the challenge of building a system that can accurately segregate chromosomes with vast structural and size differences (as much as 5x in humans and 46x in Drosophila). When chromosome segregation fails, the result is aneuploid gametes, which have either too many or too few chromosomes. Aneuploidy is a leading cause of human infertility, miscarriages, and birth defects.
We are broadly interested in understanding what makes chromosomes behave in unique ways. This is relevant not only to the reproductive failure that arises when chromosomes missegregate but also to basic chromosomal biology. We combine advanced microscopy with the wealth of genetic and genomic tools available in Drosophila, to investigate how chromosome-specific behaviors contribute to meiotic failure and infertility. Below are some questions we are currently interested in.
We are broadly interested in understanding what makes chromosomes behave in unique ways. This is relevant not only to the reproductive failure that arises when chromosomes missegregate but also to basic chromosomal biology. We combine advanced microscopy with the wealth of genetic and genomic tools available in Drosophila, to investigate how chromosome-specific behaviors contribute to meiotic failure and infertility. Below are some questions we are currently interested in.
How is the recombination landscape established?
In early meiosis, homologous chromosomes pair prior to the formation of large numbers of programmed DNA double-strand breaks (DSBs). A subset of DSBs are then repaired to form crossovers in a regulated process. However, the molecular mechanisms that determine which DSBs become crossovers remain unclear. This regulation likely involves a variety of factors including the local environment surrounding the break. We have a set of mutants that suggests that the synaptonemal complex regulates crossover location in Drosophila.
How does chromosome structure drive meiotic phenotypes?
Within a species, chromosomes often have varying structures (i.e. size and centromere placement/identity) and individuals can carry rearranged chromosomes such as end-to-end chromosome fusions (Robertsonian translocations in humans, 1 in 1,000 live births), which can cause aneuploidy-related fertility issues. It remains unknown how the vast diversity in chromosome structure affects the recombination landscape and chromosome segregation efficiency. In our system there is a difference in the recombination defects that occur on the X chromosome (one long arm) versus the autosomes (two long arms). This suggests that chromosome structure may be a factor in how and why missegregation occurs.
How are chromosome-specific meiotic behaviors regulated?
Our work has uncovered a novel defect during meiosis specific to the X chromosome. While many regulators of general meiotic behavior are known, no similar phenotypes have previously been observed in Drosophila. However, some non-meiotic regulators of the X chromosome, such as dosage compensation, do exist. In C. elegans, the X chromosome is also specifically regulated during meiosis. Identifying regulators of chromosome-specific behaviors in Drosophila will lead to a mechanistic understanding of why some chromosomes behave differently than others during meiosis.