Deciphering how directional cues are relayed into polarized collective cell migration
NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases
About This Grant
Project Summary Cells within epithelial sheets undergo collective cell migration during a variety of processes including tissue morphogenesis, organ homeostasis, and cancer metastasis. However, we lack a clear understanding of how epithelial collectives sense directional cues and translate them into polarized movements, particularly in vertebrates. Through the proposed project, I will establish the zebrafish pronephros (embryonic kidney) as a tractable, in vivo model of epithelial collective cell migration. During development, the epithelial cells of the pronephric duct undergo a collective cell migration towards the anterior of the embryo, driving morphogenesis of the proximal tubule. This migration is powered by the extension and retraction of migratory protrusions at the basal cell surface. Lumenal fluid flow has been identified as the directional cue that dictates migration orientation: pronephric epithelial cells migrate against flow. Therefore, the pronephric epithelium is an ideal yet underutilized system to study how cells sense and relay directional information during collective migration, as both the upstream polarizing cue (fluid flow) and the downstream readout (anterior migration) are known. Collective migration is often regulated by polarity modules that coordinate cytoskeletal behaviors. I hypothesize that the zebrafish Fat1a/LarA/LarB proteins function as a migratory polarity module that orients pronephric protrusions in a flow-dependent manner. In Aim 1, I will test this hypothesis through live-imaging of migration in wildtype and polarity-mutant embryos. By mechanically altering pronephric flow in embryos expressing tagged polarity proteins, I will determine if the Fat1a/LarA/LarB polarity module localizes in a flow-dependent manner. Cilia have long been speculated to function as flow sensors in the pronephric epithelium. I hypothesize that mechanosensitive sensory cilia detect flow via the Pkd2/calcium signaling pathway. In Aim 2, I will test this hypothesis by performing live calcium imaging to ascertain if there is a population of cilia exhibiting flow- responsive calcium signaling. Engineering of a ciliary-trafficking Pkd2-mutant will reveal if ciliary Pkd2 is required for migration. Together, the proposed experiments will shed light on how epithelial cells translate directional cues into polarized migration, advancing our understanding of kidney development. Moreover, through completion of these aims, I will learn essential skills in zebrafish genetics, molecular cloning, and live-imaging that will be key to the success of my future independent research lab.
Grant Summary
Deciphering how directional cues are relayed into polarized collective cell migration is a NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases grant providing up to $76K for university, nonprofit, healthcare org. Applications are due 2028-11-30 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $76K
2028-11-30
- 1Confirm your organization is eligible for Deciphering how directional cues are relayed into polarized collective cell migration from NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases before the deadline.
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Deciphering how directional cues are relayed into polarized collective cell migration: Frequently Asked Questions
Who is eligible for the Deciphering how directional cues are relayed into polarized collective cell migration?
Deciphering how directional cues are relayed into polarized collective cell migration is offered by NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Deciphering how directional cues are relayed into polarized collective cell migration provide?
Deciphering how directional cues are relayed into polarized collective cell migration provides up to $76K per award from NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Deciphering how directional cues are relayed into polarized collective cell migration deadline?
Applications for Deciphering how directional cues are relayed into polarized collective cell migration are due 2028-11-30 (open). Because deadlines can change, verify the date with the funder, NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Deciphering how directional cues are relayed into polarized collective cell migration?
To apply for Deciphering how directional cues are relayed into polarized collective cell migration, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases.