# Microbial mobilization of the actin cytoskeleton

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $476,685

## Abstract

PROJECT SUMMARY/ABSTRACT
The actin cytoskeleton is crucial for cellular properties and behaviors including shape, migration, and division. It
is also critical for cell-cell and cell-extracellular matrix connections as well as cell-cell fusion. Because of these
numerous essential functions in cell physiology, actin dysfunction is also a common contributor to pathogenesis,
for example, in inflammation, cardiovascular disease, cancer metastasis, and microbial infection. Despite many
years of study, however, understanding how actin assembly is regulated and harnessed in the cytoplasm and
nucleus for intracellular events, cellular behaviors, and cell-cell interactions remains a key outstanding problem
in cell biology. In our NIGMS-funded research, my lab has taken a distinctive approach to address this important
gap in knowledge, which is to examine the interactions between microbes that do not cause serious human
illness and the host cell actin cytoskeleton as a window into actin regulation and function. Our approach
leverages the fact that microbes colonize host cells through their ability to target actin, often eliciting amplified
cellular responses by mimicking or manipulating host molecules, making them powerful tools for revealing
molecular mechanisms of actin regulation and function. This scientific premise is supported by many examples
of how studying microbe-host interactions has enhanced our understanding of basic cell biological processes.
The research described in this MIRA application makes use of microbes as tools to address three fundamental
cell biological questions: (1) How is actin polymerization at membranes regulated and mobilized to drive
movement? (2) How and why is actin transported into and polymerized within the nucleus for gene expression,
nuclear organization, intranuclear movement, and nuclear envelope dynamics? (3) How is actin polymerization
in plasma membrane protrusions harnessed to induce cell-cell fusion? We will investigate these questions using
three model microbes that infect cells and mobilize actin in a manner that makes them powerful cell biological
tools: Mycobacterium marinum as a tool to understand the regulation of actin assembly at membranes to drive
intracellular movement; the baculovirus Autographa californica multiple nucleopolyhedrovirus as a tool to
understand the regulation and function of actin in the nucleus; and Burkholderia thailandensis as a tool to
understand the role of actin in cell-cell fusion. By leveraging our expertise in both cell biology and microbiology,
and deploying a synergistic combination of microbial and host genetic methods, advanced imaging approaches,
and biochemical methods, we are uniquely positioned to advance the field. Our results will enhance our
understanding of the mechanisms of actin regulation and may provide new insights into diagnosing, treating, and
preventing diseases associated with actin dysfunction.

## Key facts

- **NIH application ID:** 10817771
- **Project number:** 5R35GM127108-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Matthew D Welch
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $476,685
- **Award type:** 5
- **Project period:** 2018-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10817771

## Citation

> US National Institutes of Health, RePORTER application 10817771, Microbial mobilization of the actin cytoskeleton (5R35GM127108-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10817771. Licensed CC0.

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