# Elucidating the network design principles of biological signal processing

> **NIH NIH R35** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $205,527

## Abstract

Project Summary
Cells live in diverse environments, from the cells in our bodies to single-celled organisms surviving in the soil. In
order 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 the environment to the activity of intracellular effectors, such as transcription
factors, to generate an appropriate cellular response or state. Understanding this signal processing represents
a key gap in our knowledge of how healthy and diseased cells make decisions in response to stimuli. Specifically,
we ask (1) How do signaling networks transform extracellular signals into appropriate intracellular signals? and
(2) How are intracellular signals interpreted by the cell to generate appropriate responses?
My research uses Saccharomyces cerevisiae, or budding yeast, as a model organism for addressing these
questions in biological signal processing. Budding yeast exists as a unicellular microbe and therefore must be
exquisitely aware of its environment in order to survive and compete with neighboring cells. Our research is
focused on understanding signaling specificity and kinetics in the mitogen-activated kinase (MAPK) pathways
as well as transcription factor regulation 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. Furthermore, we have developed and continue to develop exquisite tools for controlling and
perturbing biological networks in Saccharomyces cerevisiae, making this an ideal system in which to address
the aforementioned questions.
We take a multi-pronged approach. We develop 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.

## Key facts

- **NIH application ID:** 10580291
- **Project number:** 3R35GM128873-05S1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Megan N McClean
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $205,527
- **Award type:** 3
- **Project period:** 2018-07-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10580291

## Citation

> US National Institutes of Health, RePORTER application 10580291, Elucidating the network design principles of biological signal processing (3R35GM128873-05S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10580291. Licensed CC0.

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