# Molecular Control of Meiotic Chromosome Dynamics

> **NIH NIH R35** · JOHNS HOPKINS UNIVERSITY · 2024 · $394,837

## Abstract

Project Summary/Abstract
 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 drive and coordinate
chromosome dynamics. Our research program will investigate these fundamental processes by combining
biochemical analysis using purified components, with the ability to examine meiosis in the context of highly
tractable C. elegans germline. One major focus of our work is the synaptonemal complex (SC), a proteinaceous
scaffold that assembles between paired homologous chromosomes. The SC is a hallmark of meiotic prophase
and yet plays a poorly understood role in regulating crossover recombination. Although genetic and cytological
studies have identified SC proteins in various organism, how individual components interact with each other to
form the regular, repetitive arrangement of the SC is largely unknown. The recent discovery of two novel SC
components in C. elegans, SYP-5 and SYP-6, has uniquely positioned our group to investigate the structure and
functions of the SC. We will refine our purification protocols to isolate SYP protein complexes and determine the
stoichiometry and protein-protein interactions among the SC components. This work will reveal the molecular
map of the SC, which will provide a foundation for understanding its conserved structure throughout eukaryotes.
In parallel, we will delineate the signaling cascades by key cell cycle kinases and phosphatases to establish key
regulatory mechanisms that govern homolog pairing, synapsis, and meiotic recombination. We will determine
the mechanisms by which PLK-2 regulates the dynamic properties of the SC and its affinity to pro-crossover
factors. We will also decipher how the CDK multisite phosphorylation code elicits a switch-like response and
mediates crossover designation. Our studies will illuminate the mechanisms underlying meiotic chromosome
behavior to a biochemical level and ultimately shed light into how organisms faithfully transmit genetic information
from parent to progeny.

## Key facts

- **NIH application ID:** 10873282
- **Project number:** 5R35GM124895-08
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Yumi Kim
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $394,837
- **Award type:** 5
- **Project period:** 2017-09-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10873282

## Citation

> US National Institutes of Health, RePORTER application 10873282, Molecular Control of Meiotic Chromosome Dynamics (5R35GM124895-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10873282. Licensed CC0.

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