# The systems biology of mitotic checkpoint signaling and its relevance to cancer cell biology

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $534,521

## Abstract

Project Summary:
The Spindle Assembly Checkpoint (SAC) is a cell cycle control that ensures accurate
chromosome segregation during cell division. It is activated by unattached kinetochores, which
recruit many different signaling proteins to produce an inhibitory signal that delays anaphase
onset and averts chromosome missegregation. Aberrant SAC signaling has long been suspected
to promote genome instability in cancerous cells, but the nature of the aberrations and their
consequences remain unclear. We propose that the perturbation of SAC signaling dynamics can
elevate chromosome missegregation. However, the SAC has been mainly studied under quasi
stead-state conditions despite being a dynamical process. Therefore, we will tackle questions
central to SAC signaling dynamics using a systems biological approach that integrates
quantitative data and mathematical modeling. Our goal is to answer the following fundamental
questions using a combination of experiments and theoretical modeling: What is the rate at which
a single unattached kinetochore generates the ‘wait-anaphase’ signal? Does it change over the
course of cell division? Is it sufficiently high to delay anaphase onset indefinitely? What are the
main determinants of this rate? Answers to these questions will reveal a dynamical picture of SAC
signaling and allow us to define the causes and consequences of aberrant SAC signaling in
cancer cells.

## Key facts

- **NIH application ID:** 10912436
- **Project number:** 5R35GM126983-07
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Ajit Joglekar
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $534,521
- **Award type:** 5
- **Project period:** 2018-07-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10912436

## Citation

> US National Institutes of Health, RePORTER application 10912436, The systems biology of mitotic checkpoint signaling and its relevance to cancer cell biology (5R35GM126983-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10912436. Licensed CC0.

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