# Molecular Mechanism and Regulation of Meiosis

> **NIH NIH R35** · UNIVERSITY OF PENNSYLVANIA · 2024 · $100,000

## Abstract

Project Summary
In sexually reproducing organisms, meiosis reduces the chromosome complement by half to generate haploid
gametes. During meiosis, homologous chromosomes undergo pairing, synapsis, recombination, and faithful
segregation. As such, defects in meiosis are a leading cause of both infertility and birth defects in humans. While
a large number of meiosis-specific factors are involved, ubiquitously expressed factors also play critical roles.
The meiotic process is generally conserved from single-cell eukaryotes to multicellular metazoans; however,
species-specific meiosis factors and functions have evolved. Our genomic and proteomic screens have identified
a large number of novel mammalian meiosis factors and we plan to determine the molecular function of a number
of key factors in the regulation of meiosis in both sexes. Meiotic recombination is essential for genome integrity
in gametes and critical for genome evolution by increasing genetic diversity at the population level. Meiotic
recombination begins with formation of meiotic DNA double strand breaks (DSBs). There are major knowledge
gaps in our understanding of this meiotic process. One main challenge is to understand the mechanism that
prevents meiotic DSB formation from getting out of control. Only a subset of the meiotic DSBs are processed
into crossovers by a large protein network. What is the molecular mechanism underlining the crosstalk in this
protein network? What additional proteins are involved in the processing of DSBs into crossovers? In many
species, chromosomal synapsis is tightly coupled with meiotic recombination. However, the process of synapsis
initiation and maintenance remains poorly understood. These challenges will be tackled in this application
through deciphering novel molecular networks underlying regulation of mammalian meiosis. Our innovative
combination of genetic, genomic, proteomic, cell/molecular biological, and biochemical approaches will focus on
the following critical but challenging aspects of meiosis: initiation of meiotic DNA double strand breaks, regulation
of meiotic recombination, initiation and maintenance of chromosomal synapsis, and origin of sex chromosome
aneuploidy. Completion of the proposed studies will provide novel mechanistic insights into key meiotic
processes, identify new candidate fertility factors, and elucidate the molecular etiology of sex chromosome
aneuploidy.

## Key facts

- **NIH application ID:** 11099080
- **Project number:** 3R35GM153384-01S1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Peijing Jeremy Wang
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $100,000
- **Award type:** 3
- **Project period:** 2024-03-15 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11099080

## Citation

> US National Institutes of Health, RePORTER application 11099080, Molecular Mechanism and Regulation of Meiosis (3R35GM153384-01S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/11099080. Licensed CC0.

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