# Chromosome structural variants in meiosis - Equipment supplement

> **NIH NIH R35** · CASE WESTERN RESERVE UNIVERSITY · 2024 · $54,133

## Abstract

Meiosis is the keystone of reproductive success in sexually reproductive organisms as failure to
successfully complete meiosis results in aneuploidy, a leading cause of developmental diseases and
miscarriages. Successful chromosome segregation is facilitated by using DNA recombination to form
crossovers (COs) between homologous chromosomes. Not all recombination events result in a CO
however and the majority are repaired as noncrossovers (NCOs). Thus, the decision whether to form a CO
or NCO is a critical regulatory point during meiosis that is poorly understood. Despite having a clear
picture of the genetic requirements for a crossover to form, it is completely unknown why some breaks
are chosen to be repaired as crossovers and others as noncrossovers. The parent grant of the current
equipment supplement addresses this critical knowledge gap by using heterozygous chromosome
inversions in Drosophila melanogaster as a model. Heterozygous inversions pose an interesting problem
for the meiotic program. Meiosis requires that homologous chromosomes recognize and use each other
as templates for precise repair during recombination, yet inversions disrupt the synteny between
homologs. There are two downstream effects: COs are suppressed locally on the inversion chromosome,
and a checkpoint is activated, which leads to a genome-wide increase in COs on non-inverted
chromosomes. We have shown that these responses are mediated through changing the CO vs. NCO
decision. In this equipment supplement, we are requesting funds to purchase the Imaris image
analysis software from Oxford Instruments. We currently have the microscopes we need (including a
Leica Stellaris 5 confocal owned by us and housed in our lab, and access to a Leica TCS SP8 gated STED
microscope housed in the CWRU Light Microscopy Core), but we do not have access to Imaris. Along with
the purchase of the software, we are also requesting funds for 3 years of the maintenance plan that will
include unlimited technical training and support for applications specific to our use case. Purchase of this
software will generate data critical for analyzing the structure of the synaptonemal complex at
inversion breakpoints and insight into defects in the structure that alter the CO/NCO decision, a high-
priority goal of the parent grant. Importantly, the methods we are proposing have been successfully
carried out by other Drosophila meiosis labs multiple times; we will be applying those methods to our
own system.

## Key facts

- **NIH application ID:** 11043080
- **Project number:** 3R35GM137834-05S1
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Kimberly Nicole Crown
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $54,133
- **Award type:** 3
- **Project period:** 2020-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11043080

## Citation

> US National Institutes of Health, RePORTER application 11043080, Chromosome structural variants in meiosis - Equipment supplement (3R35GM137834-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11043080. Licensed CC0.

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