# Actin Cytoskeleton Network Self-Organization

> **NIH NIH R35** · UNIVERSITY OF CHICAGO · 2024 · $351,769

## Abstract

PROJECT ABSTRACT
Cells assemble functionally diverse actin cytoskeleton networks with distinct architectures and
dynamics to drive fundamental processes such as polarization, motility, and division. The size,
organization, and dynamics of different actin filament networks are tailored by the coordinated
activity of distinct but overlapping sets of actin-binding proteins with complementary binding
properties. Because cells assemble and maintain multiple self-organized F-actin networks
simultaneously from the same pool of limited cellular components, focusing on single networks
provides limited overall understanding of actin cytoskeletal dynamics. We have established
important cross-talk interactions between diverse F-actin networks that help dictate their size,
form, and function. We use systems level approaches to investigate the underlying molecular
mechanisms that govern the direct and indirect interactions between self-organized F-actin
networks that determine their unique identities and functions within a common cytoplasm.
 We are focusing on two major outstanding questions relating to actin cytoskeleton self-
organization, which we are simultaneously addressing in both fission yeast cells and one-cell
C.elegans embryos to compare key mechanistic similarities and differences between these
important model systems. The first is to determine how cells allocate actin monomers between
competing F-actin networks to help tune network size and density (Focus 1). Although
unassembled G-actin was not thought to be limiting, we systematically showed that competition
for G-actin helps control the size and density of competitive F-actin networks in fission yeast, and
that the actin monomer protein profilin plays a major role in regulating competition for limiting G-
actin. Our goal is to determine the underlying mechanisms by which actin-binding proteins (ABPs)
contribute to the proper distribution of G-actin between functionally diverse actin cytoskeleton
networks. The second is to elucidate how F-actin networks recruit the specific set of ABPs whose
biochemical activities define the unique characteristics of each network (Focus 2). We will
investigate the underlying intrinsic molecular mechanisms by which ABPs self-sort to particular
F-actin networks within a common cytoplasm, including (1) the contribution of competition and
cooperation between ABPs for associating with actin filaments, and (2) whether actin assembly
factors initiate self-sorting by biasing the association of particular ABPs.

## Key facts

- **NIH application ID:** 10842871
- **Project number:** 1R35GM153234-01
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** David R Kovar
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $351,769
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842871

## Citation

> US National Institutes of Health, RePORTER application 10842871, Actin Cytoskeleton Network Self-Organization (1R35GM153234-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10842871. Licensed CC0.

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