# Elucidating the network design principles of biological signal processing

> **NIH NIH R35** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $240,329

## 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 understanding 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:** 10134043
- **Project number:** 3R35GM128873-03S1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Megan N McClean
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $240,329
- **Award type:** 3
- **Project period:** 2018-07-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134043

## Citation

> US National Institutes of Health, RePORTER application 10134043, Elucidating the network design principles of biological signal processing (3R35GM128873-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10134043. Licensed CC0.

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