# Conflict-driven aneuploidy and genomic instability caused by meiotic proteins

> **NIH NIH K00** · HARVARD UNIVERSITY · 2020 · $85,666

## Abstract

PROJECT SUMMARY/ ABSTRACT
Chromosome segregation can fail and generate cells with too many or too few chromosomes, a condition
known as aneuploidy. Aneuploidy is a driving force in cancer progression and most cancers exhibit an
abnormal karyotype. Aneuploidy is also the leading cause of infertility and congenital birth defects, such as
Down syndrome. Because of the prevalence of aneuploidy in cancer and infertility, it is paramount to
understand the causes of inaccurate chromosome segregation. Some components of the chromosome
segregation machinery are among the fastest evolving genes in the genome. This rapid evolution is
paradoxical as the process of chromosome segregation is essential and largely conserved. It is thought that
conflicts caused by genetic parasites, found throughout eukaryotes, could be one cause of this rapid evolution.
Meiotic drivers are one such type of intragenomic parasites that selfishly promote their own transmission into
gametes. The overall goal of this proposal is to identify mechanisms that cause aneuploidy and infertility. The
proposed aims will address three important questions: 1) What are the molecular mechanisms utilized by
meiotic drivers? 2) Do meiotic drivers promote the formation of aneuploid gametes? 3) What causes errors in
chromosome segregation? My work recently identified fission yeast wtf genes as a tractable model system in
which to study meiotic drive. For my thesis dissertation (Aim 1), I will test if the genetic conflict caused by these
meiotic drivers could affect the chromosome segregation machinery and thus the frequency of aneuploid
gametes. Additionally, I will test if a high frequency of meiotic drivers in a population could promote the
evolution of low fidelity chromosome segregation. During my postdoctoral research (Aim 2), I will apply the
insights gained in my thesis research to address if the meiotic components of the chromosome segregation
machinery can contribute to errors in mitotic chromosome segregation in humans. In addition, I will test if the
untimely expression of meiotic genes contributes to the aneuploidy seen in cancer cells. To achieve these
goals, I will use interdisciplinary approaches such as genetics, theoretical evolution, confocal microscopy, and
cytogenetics. The completion of these aims will expand our understanding of the causes of aneuploidy and
infertility, as well as the impact that genetic conflict has on genome integrity. The proposed research
represents a unique contribution to the field of chromosome segregation and cancer research.

## Key facts

- **NIH application ID:** 10199524
- **Project number:** 4K00CA234523-03
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Maria Angelica Bravo Nunez
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $85,666
- **Award type:** 4N
- **Project period:** 2018-09-10 → 2021-06-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10199524

## Citation

> US National Institutes of Health, RePORTER application 10199524, Conflict-driven aneuploidy and genomic instability caused by meiotic proteins (4K00CA234523-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10199524. Licensed CC0.

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