Deconstructing fast amoeboid cell migration
Active Project Grant Awarded Last action
- Award ID
- R35GM157022
- Recipient
-
The Research Foundation For The State University Of New York UEI M746VC6XMNH9 Part of The Research Foundation For The State University Of New York
- Awarding agency
-
National Institute of General Medical Sciences
National Institutes of Health, Department of Health and Human Services
- Obligated
- $1,186,161
Award facts
- Assistance listing
- 93.859 Biomedical Research and Research Training
- Completion date 43% complete
- Place of performance
- Stony Brook, NY 11794, USA
Award details come from USAspending.gov.
Description
- Abstract
- Many cells can travel from one place to another. This nomadic cell behavior is harnessed to form organs, seal wounds, and hunt down pathogens, but IT is often dysregulated in human diseases, including cancer. Consequently, understanding the molecular basis of cell movement has widespread significance for human health. Decades of cell migration studies have outlined how a cell moves on a flat surface. In a two-dimensional environment, a moving cell extends a branched actin-filled protrusion in the direction of movement, while actomyosin contractility retracts the rear. However, cells can move without actin-filled protrusions in vivo using a poorly understood, three-dimensional migration mode called amoeboid migration. Amoeboid migrating cells can move by extruding pressure-filled blebs devoid of actin or rapidly migrate with a near-constant spherical shape using cortical actin flow. Cortical flow-driven amoeboid migration is commonly referred to as fast amoeboid migration (FAM) and is induced by mechanical confinement in a wide variety of cells, with an increased propensity in invasive cancer cells. The non-genetic and extensive induction of FAM, coupled with its use by cancer cells in vivo, necessitates a mechanistic understanding of its underpinnings. However, observing and perturbing FAM is technically challenging in vivo, and the plasticity with which cells can switch how they migrate can confound subsequent analysis. My lab uses the developmental migration of drosophila primordial germ cells (pgcs) as a facile, reproducible system to study FAM. Pgcs natively use FAM in vivo and, importantly, maintain the characteristic cortical actin flows that power FAM outside of the embryo in culture without mechanochemical inputs. Thus, pgcs do not alter how they move, even in a foreign two-dimensional environment. Over the next five years, we will capitalize on the inflexible nature of migratory pgcs to deconstruct FAM and address several outstanding, currently intractable questions: (1) what cortical actin architectures are permissive for cortical flows, and how are these networks assembled, regulated, and maintained? (2) how are cortical flows oriented by guidance cues to direct FAM? (3) how are cortical flows transmitted to a given substrate to generate traction for productive motility? Results from this study will shed light on a poorly understood cell migration strategy and will identify key factors to not only halt IT for therapeutic intervention but also endow other cells with its use for cell- based therapies.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $395,387 | |
| Amendment | $395,387 | |
| Original award | $395,387 |
Quick answers
Who received award R35GM157022?
R35GM157022 was awarded to The Research Foundation For The State University Of New York by National Institute of General Medical Sciences (National Institutes of Health) on September 16, 2024.
How much is award R35GM157022 worth?
$1,186,161 has been obligated on R35GM157022.
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