# Mathematical modeling of  cellular signaling systems

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $450,950

## Abstract

This project seeks to integrate computational methods, including mathematical modeling and image
analysis techniques, with quantitative experimental approaches to understand complex cellular
behavior. In particular, we investigate cellular processes, such as cell fate decisions, polarity
establishment, and gradient sensing, that are coordinated by intracellular signaling networks. The goal
of our research is to understand how these networks function as integrated systems. Mathematical
modeling is needed to understand the feedback and feed forward regulation that coordinates the
spatiotemporal dynamics of signaling pathways, and computational image analysis is needed to extract
the quantitative information from live-cell images that is required to inform and validate the models.
The primary model organism we use to study cell signaling is the yeast Saccharomyces cerevisiae. Our
investigations combine microfluidic technology with live-cell microscopy to observe cellular behavior in
well-controlled environments. This work is performed together with the labs of our longstanding
collaborators Drs. Beverly Errede, Daniel Lew and Henrik Dohlman. Established projects in the lab
include: 1) understanding molecular mechanisms involved in cell polarity and gradient sensing and 2)
identifying signaling motifs that dynamically regulate gene expression and fate decisions. An exciting
new direction for the lab is to investigate the effects of aging on cell signaling. My lab is also involved in
collaborative projects to investigate cell signaling in mammalian cells and how the dysregulation of
these pathways leads to human disease. Current projects in the lab include: 1) a longstanding
collaboration with Dr. Richard Boucher to understand how purinergic signaling maintains airway surface
liquid homeostasis and is dysregulated in cystic fibrosis, 2) a new project with our established
collaborator Dr. Klaus Hahn to understand mechanisms that coordinate signaling during phagocytosis
and 3) a new project with Dr. Ned Sharpless to understand the mechanisms that regulate cell
differentiation during hematopoiesis. The unifying theme of all these projects is the use of mathematical
modeling to understand how feedback and feed forward regulation generates coordinated
spatiotemporal behavior. The ultimate goal of our investigations is to generate truly predictive models of
in vivo cellular processes that can be applied to the rationale design of new therapeutic strategies.
!

## Key facts

- **NIH application ID:** 9997976
- **Project number:** 5R35GM127145-03
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Timothy C Elston
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $450,950
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9997976

## Citation

> US National Institutes of Health, RePORTER application 9997976, Mathematical modeling of  cellular signaling systems (5R35GM127145-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9997976. Licensed CC0.

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