# Understanding the robustness of cell cycles

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $299,097

## Abstract

Project Summary
Biological oscillators are essential to a variety of cyclic processes in cells and development. These include cell
divisions, heartbeats, and somitogenesis. Impaired biological oscillators may cause diseases from insomnia to
cancer. It is thus crucial for an oscillator to develop the ability to maintain a stable function against the changes
in environmental conditions. The architecture of many oscillators is highly conserved among species, despite
that the actual molecules may vary from species to species. This highlights the important role of network topology
in the functions of biological oscillators. How the network structure is linked to the certain functions of biological
oscillators is still an open challenging question in systems and synthetic biology. The goal of this proposal is to
identify the fundamental principles underlying the robust functioning of clock networks. To achieve the goal, a
systematic computational approach will be applied to analyze all topological modifications that significantly
impact the robustness and tunability of clock networks. As a comparison to computational studies, this proposal
will experimentally investigate the possible mechanisms by which cell cycles retain robust oscillations. The
proposed experiments make use of a droplet-based microfluidic system, where cell-free extracts are
encapsulated in droplets to mimic single cells that undergo mitotic cycles. This artificial cell system will be
integrated with live embryo imaging and stochastic modeling, to track and analyze many single oscillators
simultaneously, and thereby quantify the robustness of the mitotic cycles to environmental changes and
molecular stochasticity. To study the role of network structure in the robustness of the clock, results from intact
oscillators will be compared with the ones whose sub-networks are compromised. The results from the mitotic
clock may apply to a broad set of other clocks that share similar topological cores. The results should also provide
valuable insights on how to design a robust synthetic clock.

## Key facts

- **NIH application ID:** 10809646
- **Project number:** 5R01GM144584-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Qiong Yang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $299,097
- **Award type:** 5
- **Project period:** 2023-03-15 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10809646

## Citation

> US National Institutes of Health, RePORTER application 10809646, Understanding the robustness of cell cycles (5R01GM144584-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10809646. Licensed CC0.

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