# Elucidating the network design principles of biological signal processing

> **NIH NIH R35** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $421,501

## Abstract

Project Summary
Cells live in diverse environments and cellular communities, from the cells in our bodies to single-celled
organisms surviving in the soil. To navigate these complex environments, cells must be able to sense and
respond to a variety of signals. This is done through biological signaling pathways, consisting of sensors and
interacting proteins, which process external signals and transmit information. My research program focuses on
understanding how these biological networks transmit information about external signals to the activity of
intracellular effectors, such as transcription factors, to generate an appropriate cellular response or state and
how these cell states affect community-level phenotypes. Understanding this signal processing represents a key
gap in our knowledge of how healthy and diseased cells make decisions and guide the behavior of cellular
communities. Specifically, we ask (1) How do signaling networks transform extracellular signals into appropriate
intracellular signals? (2) How are intracellular signals interpreted by the cell to generate appropriate responses?
and (3) How do individual cell decisions affect population-level community phenotypes?
Our research is focused on understanding signaling specificity and kinetics in the mitogen-activated kinase
(MAPK) pathways as well as transcription factor dynamics and subsequent gene expression in response to
environmental stress. MAP kinase pathways are conserved from yeast to humans and control vital cellular
processes including proliferation, differentiation, and stress response. We use a variety of systems to address
the questions outlined in this research proposal including Saccharomyces cerevisiae, the human fugal pathogen
Candida albicans, synthetic signaling pathways, and mammalian cell culture. We take a multi-pronged approach
that uses microfluidic and optogenetic tools to perturb signaling pathways and combine these perturbations with
mathematical modeling to understand how different properties of signaling pathways, including bandwidth and
crosstalk, allow them to appropriately transform their input signals. Furthermore, we use these tools to drive
dynamics of intracellular effectors, such as transcription factors, and ask how these different effector dynamics
generate cellular responses. And finally, we use the exquisite spatiotemporal control available with light to
generate desired states in individual or populations of cells, including fungal biofilms, and ask how this affects
community-level phenotypes.

## Key facts

- **NIH application ID:** 10909806
- **Project number:** 5R35GM128873-07
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Megan N McClean
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $421,501
- **Award type:** 5
- **Project period:** 2018-07-15 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909806

## Citation

> US National Institutes of Health, RePORTER application 10909806, Elucidating the network design principles of biological signal processing (5R35GM128873-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10909806. Licensed CC0.

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