Sexually reproducing organisms rely on meiosis, a specialized cell division that produces haploid gametes such as sperm and eggs, to restore the genetic content of the zygote through fertilization. Errors in this process lead to the production of offspring with an abnormal number of chromosomes or aneuploidy, and this is a major cause of human miscarriages and birth defects such as Down syndrome. Accurate segregation of chromosomes during meiosis requires that they pair, synapse, and undergo crossover recombination with their homologs. Although genetic studies over the decades have identified a list of proteins that are essential for meiotic processes, it remains largely unknown how these protein machines work together to orchestrate chromosome dynamics. My research program will investigate these fundamental processes by combining biochemical and structural analysis using purified components, with the ability to examine meiosis in the context of highly tractable C. elegans germline. Early in meiosis, chromosomes are dramatically reorganized into arrays of chromatin loops tethered to a proteinaceous axis, and this is essential for all major meiotic events

Public Health Relevance

Meiosis, a specialized cell division that generates sex cells such as sperm and eggs, is essential for the inheritance of genomes from parent to offspring. Errors in this process lead to the production of cells with an abnormal number of chromosomes or aneuploidy, and this is a major cause of miscarriages and birth defects such as Down syndrome. Our findings from this study will elucidate the molecular mechanisms underlying chromosome inheritance during meiosis and will also have general impact in the fields of cell cycle regulation and cancer.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R35)
Project #
5R35GM124895-02
Application #
9552222
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Melillo, Amanda A
Project Start
2017-09-01
Project End
2022-06-30
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205