# An optogenetic toolkit for spatiotemporal control of gene expression in Candida albicans

> **NIH NIH R21** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $191,612

## Abstract

Project Summary
Life-sustaining therapies, such as central venous catheters and endotracheal tubes, disrupt the body’s natural
protective barriers (e.g. skin, mucosal membranes) and provide a natural conduit for infection. Device-associated
Candida albicans fungal infections in particular represent a devastating medical complication associated with
high mortality and high morbidity. Fungal and human cells share very similar cellular structure and machinery,
making it difficult to find drugs that aggressively target the fungal cell without significant toxicity to humans.
Additionally, as the number of patients treated for fungal infections has increased, so too has the emergence of
drug resistant Candida strains. It is crucial that unique aspects of this fungal pathogen’s biology be identified and
exploited to develop new therapies.
One unique aspect of Candida pathogenesis is the way it establishes and disseminates infection. Device
associated fungal biofilms develop when yeast-form cells adhere to substrate, initiate biofilm formation, and
mature. Dispersion of yeast-form cells from the biofilm seed new sites of infection. Candida biofilms exhibit gene
regulatory programs that vary in space and time. Currently there is a limited experimental toolbox for Candida to
explore how this dynamic, spatially heterogenous gene regulation controls the biofilm lifecycle. In this proposal
we will develop optogenetic and microfluidic tools that allow us to better understand how temporal and spatial
expression of different putative regulators control biofilm formation and dissemination.
Aim 1: Develop flexible optogenetic control of gene expression in Candida albicans We will develop
optogenetic tools that allow us to flexibly regulate gene expression in Candida albicans. This system will allow
us to repress or overexpress specific genes in Candida albicans biofilms in space and time.
Aim 2: Develop a novel in vitro assay to quantify defects in biofilm formation, dispersion and
dissemination We will develop an in vitro microfluidic system that allows us to quantify defects in the biofilm
lifecycle in response to precise spatiotemporal genetic perturbations.
The outcomes of this work will be 1) creation of optogenetic tools for flexibly targeting Candida genes for
repression or overexpression in both space and time and 2) development of a microfluidic device that lets us
quantitatively monitor the outcome of modulating specific regulators. A better understanding of the uniquely
fungal factors that regulate biofilm formation and dispersion may lead to new therapeutics targeting these factors.

## Key facts

- **NIH application ID:** 9948560
- **Project number:** 5R21AI135166-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** David R Andes
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $191,612
- **Award type:** 5
- **Project period:** 2019-06-07 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948560

## Citation

> US National Institutes of Health, RePORTER application 9948560, An optogenetic toolkit for spatiotemporal control of gene expression in Candida albicans (5R21AI135166-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9948560. Licensed CC0.

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