# Microbial mobilization of the actin cytoskeleton

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $385,154

## Abstract

PROJECT SUMMARY/ABSTRACT
The actin cytoskeleton is crucial for cellular properties and behaviors including shape, migration, and division,
as well as for cell-cell connections and fusion during animal development. 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. My lab has taken a distinctive approach to address this important gap in knowledge, which is to
examine the interactions between infectious microbes and the actin cytoskeleton as a window into actin
regulation and function. Our approach leverages the fact that many infectious microbes colonize host cells
through their ability to target actin, and builds on numerous examples of how studying the interactions between
microbes and host cells has enhanced our understanding of cytoskeleton dynamics, as well as membrane
trafficking, cell cycle regulation, protein recycling, and cell death.
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, each of which mobilizes actin in a manner that makes it a unique and powerful
instrument: 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 microbiology and cell biology,
deploying a synergistic combination of microbial and mammalian genetic methods, and employing biochemical,
biophysical and imaging approaches, we are uniquely positioned to advance the field forward. 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 including inflammatory and
cardiovascular diseases, cancer, and microbial infection.

## Key facts

- **NIH application ID:** 9912779
- **Project number:** 5R35GM127108-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Matthew D Welch
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,154
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9912779

## Citation

> US National Institutes of Health, RePORTER application 9912779, Microbial mobilization of the actin cytoskeleton (5R35GM127108-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9912779. Licensed CC0.

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