# Feedback Control of the Cell Cycle

> **NIH NIH R01** · HARVARD UNIVERSITY · 2021 · $496,695

## Abstract

Abstract
Evolution shapes the mechanisms that promote the faithful transmission of genetic information
during the reproduction of cells and organisms and errors in transmission are the raw material
that drives evolutionary adaptation. Chromosome metabolism (the combination of chromosome
replication, chromosome segregation, and the mechanisms that regulate them) changes over a
wide range of time-scales. Over millions of years, mechanisms and components change, leading
to cell biological differences between mammals and microbes that can exploited to treat infectious
and parasitic disease. Over a human lifetime, cancer cells accumulate mutations that increase
cell proliferation, survival, and migration and cause the genetic instability that accelerates cancer
evolution and produces the mutant cells that resist many therapies. In meiosis, errors in
chromosome segregation cause Down syndrome, the most common genetic birth defect. The
combination of whole genome sequencing and genome engineering to test the effects of
mutations makes experimental evolution a powerful tool to study the evolution of chromosome
metabolism, its current mechanisms, and its plasticity. The budding yeast, Saccharomyces
cerevisiae, with its rapid reproduction, compact genome, highly developed cell biology and
genetics (both classical and molecular) is an ideal organism for these studies, which have already
yielded insights into the evolution of both cancer and species. In this project, parallel populations
will be evolved to respond to genetic perturbations, genome sequencing will find putative
causative mutations, these mutations will be engineered, individually and in combination into
ancestral strains, and cell biological assays will reveal the mechanisms by which the selected
mutations repair or bypass the damaged pathways. The proposal has three aims, each studying
how a cell biological process responds to genetic perturbations, with the twin goals of learning
more about the process and its response to selective pressure: 1) Evolving improved survival and
proliferation in response to replication stress, a ubiquitous feature of cancer. 2) Evolving two
modifications of meiosis: alternative mechanisms to initiate recombination and accurate meiotic
chromosome segregation in the absence of recombination. 3) Investigating a specific hypothesis
for the mechanism of parasexuality, the process by which a variety of fungi, including pathogens
such as Candida albicans, reduce their ploidy without passing through meiosis. All three aims will
produce insights into disease, including cancer, inherited birth defects, and fungal pathogenesis.

## Key facts

- **NIH application ID:** 10261545
- **Project number:** 5R01GM043987-30
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Andrew W Murray
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $496,695
- **Award type:** 5
- **Project period:** 1990-04-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10261545

## Citation

> US National Institutes of Health, RePORTER application 10261545, Feedback Control of the Cell Cycle (5R01GM043987-30). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10261545. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*