# Meiotic Chromosome Inheritance in C. elegans

> **NIH NIH R35** · STANFORD UNIVERSITY · 2021 · $667,443

## Abstract

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 the nematode
C. elegans, a simple metazoan organism that is especially amenable to combining powerful cytological,
genetic and genomic approaches in a single experimental system, and in which the events under study are
particularly accessible. Multiple lines of research are converging on a view of meiotic prophase as a highly
integrated biological system that incorporates multiple “engineering design features” such as positive and
negative feedback, self-limiting properties, quality control and fail-safe mechanisms that together promote a
robust biological outcome. Our goal under the MIRA program is to elucidate how the different features of the
meiotic program work, both individually and as a system, through integrating the use of advanced technologies
that enable us to visualize the process (either through microscopic imaging or computational analysis of
sequence-based assays) with advantages of the C. elegans system that enable experimental perturbation of
the process. Another major long term goal is to understand the fundamental basis of homolog recognition and
the nature of the interface between aligned homologous chromosomes. We will interrogate the process of
meiosis at multiple different scales: 1) at the level of the DNA repair complexes that assemble at the sites of
meiotic recombination; 2) at the level of the meiosis-specific chromosome structures that promote, regulate
and respond to meiotic recombination events...

## Key facts

- **NIH application ID:** 10133680
- **Project number:** 5R35GM126964-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** ANNE M VILLENEUVE
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $667,443
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133680

## Citation

> US National Institutes of Health, RePORTER application 10133680, Meiotic Chromosome Inheritance in C. elegans (5R35GM126964-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10133680. Licensed CC0.

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