Actin cytoskeleton network self-organization

Active Project Grant Awarded Last action

Award ID
R35GM153234
Recipient
Awarding agency
Obligated
$3,009,376

Award facts

Assistance listing
93.859 Biomedical Research and Research Training
Completion date 46% complete
Place of performance
Chicago, IL 60637, USA

Award details come from USAspending.gov.

Description

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.

Transactions

Action Obligated Date
Amendment $70,555
Amendment $627,838
Amendment $627,838
Amendment $627,838
Amendment $0
Amendment $0
Amendment $351,769
Amendment $351,769
Original award $351,769

Quick answers

Who received award R35GM153234?

R35GM153234 was awarded to The University Of Chicago by National Institute of General Medical Sciences (National Institutes of Health) on July 1, 2024.

How much is award R35GM153234 worth?

$3,009,376 has been obligated on R35GM153234.

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