# Mathematical modeling of cellular signaling systems

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $466,907

## Abstract

Project Summary
 The important challenge this project addresses is to gain a mechanistic understanding of regulatory
elements that tightly control the spatiotemporal dynamics of intracellular signaling pathways. To meet
this challenge, we combine computational approaches, including mathematical modeling and image
analysis, with experiments performed at the single cell level. All cells must sense and respond to
changes in their environment. Environmental cues such as hormones, nutrients or physical stresses are
detected by receptors on the cell surface. This information is than processed and transmitted to
appropriate regions of the cell by intracellular signaling pathways. The proper response to a stimulus
often requires cells to change shape or move. Therefore, signaling pathways must coordinate the
dynamics of the actin cytoskeleton in both space and time. This task is accomplished through the use
of feedback and feedforward loops acting over multiple temporal and spatial scales. Because these
regulatory loops make signaling pathways inherently nonlinear, mathematical modeling is required to
understand the emergent properties of these systems. We have identified three cellular processes that
lend themselves to systems-level analysis and form the basis for our studies over the next five years: 1)
directed growth during mating and budding in the yeast S. cerevisiae and related fungi, 2)
phagocytosis, the process through which cells sense and ingest bacteria and other objects, and 3)
collective migration in which a group of cells move as a single unit. These projects represent the
continuation of established collaborations and exciting new directions for my lab. We will continue our
collaboration with the lab of Dr. Daniel Lew (Duke, Pharmacology and Cancer Biology) to understand
the mechanisms that underlie polarity establishment and gradient sensing in S. cerevisiae. In a new
collaboration with Dr, Amy Gladfelter (UNC, Biology), we will investigate if similar mechanisms play a
role in the establishment of multiple polarity sites by the fungus Aureobasidium pullulans. We also will
continue our long-standing collaboration with the lab of Dr. Klaus Hahn (UNC, Pharmacology) to
investigate the mechanisms that underlie spatial patterning during phagocytosis. Finally, we have
recently established a new collaboration with Dr. Scott Magness (UNC, BME) to investigate epithelial
polarization during collective migration. The goal of our investigations is to generate truly predictive
models of in vivo cellular processes that ultimately provide insights into the etiology and treatment of
human diseases.

## Key facts

- **NIH application ID:** 10892028
- **Project number:** 5R35GM127145-07
- **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:** 2024
- **Award amount:** $466,907
- **Award type:** 5
- **Project period:** 2018-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892028

## Citation

> US National Institutes of Health, RePORTER application 10892028, Mathematical modeling of cellular signaling systems (5R35GM127145-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10892028. Licensed CC0.

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