# Evolution of Stress Response Gene Regulatory Network in a Commensal and Opportunistic Yeast Pathogen

> **NIH NIH R35** · UNIVERSITY OF IOWA · 2020 · $369,726

## Abstract

Gene regulatory evolution is a major driver for phenotypic divergence. While this has been well-studied in
development, its importance in non-developmental processes is far less understood. The overall vision
of the lab is to fully characterize the evolutionary rewiring of gene regulatory networks (GRNs) for
major stress responses in opportunistic yeast pathogens, and elucidate the contribution of such
changes to the survival and virulence in the host. The lab previously discovered a significant difference
in how a commensal and opportunistic yeast pathogen, Candida glabrata, regulates its Phosphate
Starvation (PHO) response compared with its non-commensal relative, Saccharomyces cerevisiae: the
commensal has dramatically expanded its PHO response targets both in number and in function, which
was attributed to derived changes in its master transcription factor (TF) by being less dependent on the
co-TF. The goal of the lab in the next five years is to determine the genetic and mechanistic bases of this
novel mode of TF evolution, i.e. acquiring new targets by reducing co-TF dependence, and the effect of
such evolution on stress resistance to phosphate starvation as well as combinatorial stresses in the host.
Understanding how this model stress response evolved by itself and in its interaction with other stress
responses will begin to elucidate the principles for stress response evolution in commensal yeasts in
general. To reach this goal, three Directions will be pursued: 1) Elucidate the mechanisms of a novel mode
of TF evolution and its impact on the downstream response, using biophysical and fitness assays; 2)
Dissect the crosstalk between stress responses and how it evolved in commensal yeasts, by determining
the interaction of PHO response with oxidative stress and general stress responses in C. glabrata and S.
cerevisiae; 3) Determine how the PHO network evolved in other commensal yeasts and related non-
commensals, using transcriptome profiling coupled with genome-wide Chromatin-IP. Research proposed
in this application is innovative because the evolutionary approach will identify key changes in the wiring
of the stress response GRNs underlying host adaptation. The proposed research is significant because it
will both shed light on the general principles for GRN evolution, and will provide a conceptual framework
for developing novel antifungal strategies targeting stress responses.

## Key facts

- **NIH application ID:** 10026476
- **Project number:** 1R35GM137831-01
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Bin Z He
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $369,726
- **Award type:** 1
- **Project period:** 2020-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10026476

## Citation

> US National Institutes of Health, RePORTER application 10026476, Evolution of Stress Response Gene Regulatory Network in a Commensal and Opportunistic Yeast Pathogen (1R35GM137831-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10026476. Licensed CC0.

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