# Structure and dynamics of meiotic chromosomes

> **NIH NIH R35** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $381,248

## Abstract

Chromosome segregation during meiosis places one chromosome, either the maternal or paternal copy, in
each gamete. Accurate segregation of genetic material requires that the parental chromosomes interact with
one another and exchange genetic information through the formation of crossovers. Crossover formation
requires that chromosomes undergo an orchestrated series of morphological transformations. Failure to make
crossovers leads to errors in meiotic chromosome segregation, and consequently to infertility and congenital
birth defects. The research proposed here will use nematodes and budding yeast to address the mechanisms
of chromosome interaction and segregation by employing experimental approaches that take advantage of the
unique features of these model systems, including direct imaging of chromosome dynamics in living animals.
The molecular mechanisms that allow chromosomes to form, regulate, and respond to crossovers are poorly
understood. This proposal probes three aspects of meiotic chromosome organization and dynamics. The first
project will explore how the Synaptonemal Complex (SC)—a conserved structure that assembles between
homologous chromosomes and regulates the distribution of crossovers—implements chromosome-wide
regulation. This work builds on the recent understanding that the SC, despite its ordered appearance when
visualized by electron microscopy, is a liquid-like phase-separated compartment. A novel mutagenesis and
genetic screening strategy will isolate separation-of-function mutations that perturb the liquid properties of the
SC, and in that way assign specific functions to SC components. In addition, poorly understood chromosome-
wide SC dynamics will be directly visualized for the first time using long-term live-imaging. A mechanistic
understanding of these dynamics will explain how the meiotic program responds to karyotype abnormalities,
and how the SC regulates, and responds to, crossovers.
The second project focuses on the reorganization of the chromosomes that transforms crossovers—a local
exchange of DNA strands—into the connections that hold the parental chromosomes together during the
meiotic divisions, and promotes their correct segregation into gametes. A novel way to label only one of the
two parental chromosomes and to visualize its morphology throughout meiosis will rely on the advantageous
organization of chromosomes in the C. elegans gonad and on super-resolution microscopy.
The third project addresses the organization of meiotic chromosomes as loops of chromatin that are anchored
at their base to a proteinaceous axis. This conserved chromosome organization is integral to the meiotic
program, but the mechanisms regulating its assembly and dynamics remain enigmatic. A novel technique to
obtain a high-resolution description of chromosome conformation and dynamics in budding yeast will take
advantage of an emerging technology to sequence very long molecules of DNA. This technique could be
widely applied to pro...

## Key facts

- **NIH application ID:** 9975180
- **Project number:** 5R35GM128804-03
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Ofer Rog
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,248
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975180

## Citation

> US National Institutes of Health, RePORTER application 9975180, Structure and dynamics of meiotic chromosomes (5R35GM128804-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9975180. Licensed CC0.

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