# Structural-Functional Basis of Actin Cytoskeleton Dynamics

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $411,695

## Abstract

Summary
The actin cytoskeleton is a highly dynamic system consisting of hundreds of proteins. Cells use
the actin cytoskeleton to move, divide, transport organelles and exchange materials with the
environment. Many human diseases result from malfunctioning of actin cytoskeletal
components. There is therefore intense interest in understanding molecular mechanisms that
control actin cytoskeletal processes, which has both fundamental importance and the potential
to accelerate the development of targeted therapies to treat human diseases. Among actin
cytoskeletal components, none is more important than Arp2/3 complex, a 7-subunit actin
filament nucleation and branching system conserved in eukaryotes from yeast to human. This
grant addresses important gaps of knowledge of the mechanisms of Arp2/3 complex
activation, inhibition, branch stabilization, and branch destabilization. Published work,
extensive preliminary studies presented in the application, and new advances in the laboratory
such as the implementation of cryo-electron microscopy (cryo-EM) to the Arp2/3 complex
system, and innovative protein expression methods and biochemical assays provide the
scientific and technical premises supporting the research plans. The specific aims focus on three
major areas: 1) understand the molecular determinants of human Arp2/3 complex branch
stability and mechanosensation using a microfluidics-TIRF microscopy assay, 2) determine the
structural-functional mechanism of branch stabilization by cortactin using biochemical methods
and cryo-EM, and 3) uncover whether one of the members of the coronin family acts as an
Arp2/3 complex inhibitor, a branch stabilizer, or a branch destabilizer using biochemical
approaches and cryo-EM

## Key facts

- **NIH application ID:** 10811725
- **Project number:** 5R01GM073791-19
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** ROBERTO DOMINGUEZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $411,695
- **Award type:** 5
- **Project period:** 2005-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10811725

## Citation

> US National Institutes of Health, RePORTER application 10811725, Structural-Functional Basis of Actin Cytoskeleton Dynamics (5R01GM073791-19). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10811725. Licensed CC0.

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