# Meiotic Chromosome Inheritance in Caenorhabditis

> **NIH NIH R35** · STANFORD UNIVERSITY · 2023 · $807,994

## Abstract

Program Summary
Our research is aimed at understanding the molecular and cellular mechanisms underlying the faithful
inheritance eukaryotic chromosomes. Our primary focus is on elucidating the events required for the orderly
segregation of homologous chromosomes during meiosis, the crucial process by which diploid germ cells
generate haploid gametes. These events are of central importance to sexually reproducing organisms, since
failure to execute them correctly leads to chromosomal aneuploidy, one of the leading causes of miscarriages
and birth defects in humans. During meiotic prophase, chromosomes undergo a dramatic and dynamic program
of structural reorganization in preparation for the meiotic divisions. Moreover, chromosome inheritance during
meiosis relies on the formation of double-strand DNA breaks (DSBs) and repair of a subset of these DSBs as
inter-homolog crossovers (COs). Because the DSBs that serve as the initiating events of meiotic recombination
pose a danger to genome integrity, the success of genome inheritance during meiosis requires cells to maintain
a balance between the beneficial effects of COs and the potential harmful consequences of the process by which
they are generated. A major goal of our research is to understand the mechanisms that operate during meiosis
to achieve this crucial balance. An inter-related goal is to understand how meiosis-specific chromosome
organization is established, maintained, and remodeled to bring about successful segregation of homologous
chromosomes. We are approaching these issues using Caenorhabditis nematodes, simple metazoan organisms
that are especially amenable to an integrated application of powerful cytological, genetic, genomic, and
biochemical approaches, and in which the events under study are particularly accessible. Our goal under the
MIRA program is to pursue a systems-level understanding of meiosis, based on the recognition that multiple
distinct aspects of the meiotic program are intimately interconnected, and that robustness of the system is an
emergent property of this interconnectedness. Our approach will build on recent technical advances and new
discoveries in the well-established C. elegans experimental system, in combination with opportunities afforded
by a newly-introduced Caenorhabditis interspecies hybrid model, to interrogate the meiotic program at multiple
levels. Planned areas of investigation will include: Elucidating mechanisms that ensure reliable formation of CO-
based connections for all chromosome pairs; Exploring how different events and developmental transitions in
the meiotic program are temporally and spatially coordinated; Investigating the functional organization of
meiosis-specific chromosome structures that promote and regulate meiotic recombination and enable
chromosomes to sense and respond to events occurring at distant positions; Pursuing a new approach aimed at
understanding the fundamental basis of homolog recognition.

## Key facts

- **NIH application ID:** 10623710
- **Project number:** 2R35GM126964-06
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** ANNE M VILLENEUVE
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $807,994
- **Award type:** 2
- **Project period:** 2018-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10623710

## Citation

> US National Institutes of Health, RePORTER application 10623710, Meiotic Chromosome Inheritance in Caenorhabditis (2R35GM126964-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10623710. Licensed CC0.

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