Defining the PS neighborhood proteins on apoptotic cells and their impact on efferocytosis
About This Grant
Abstract Phosphatidylserine (PS), which constitutes only 2-10% of plasma membrane lipids, is a key phospholipid involved in intercellular communication/signaling. PS is actively sequestered to the inner leaflet of the plasma membrane and cells spend significant energy to maintain this asymmetry. PS externalization to the outer leaflet under specific contexts, such as after induction of apoptosis, allows phagocytes to recognize and engulf the dying cells via efferocytosis. Further, the engagement of PS on apoptotic cells by PS receptors on phagocytes (such as macrophages) induces anti-inflammatory signaling, which is a hallmark of efferocytosis during homeostasis. Despite our recognition of PS as a key apoptotic marker, nearly all studies consider PS as an isolated entity, and the PS-proximal proteins influencing PS recognition and signaling remain largely unexplored. Our exciting preliminary studies reveal that PS exposure on apoptotic cells occurs in patches and occurs adjacent to specific proteins, which can, in turn, influence efferocytosis. Our overarching hypothesis tested in this proposal is that proteins in the PS neighborhood on apoptotic cells critically influence/modulate the efferocytosis of dying cells, and the downstream signaling/responses elicited within phagocytes. In Aim 1, based on preliminary data identifying specific PS-proximal proteins, we test how they differ between apoptotic versus 'live’ cells engineered to expose PS (without caspase activation), the proximity of PS to specific scramblases that mediate PS exposure, and how different cell death modalities may alter PS- proximal proteins. In Aim 2, we test specific PS-proximal tetraspanin proteins in regulating efferocytosis ex vivo and in vivo, via models of tissue inflammation. The novel approaches taken here to define the PS neighborhood on apoptotic cells and its influence on efferocytosis address a long-standing key gap in our knowledge, with relevance to auto-inflammatory diseases.
Grant Summary
Defining the PS neighborhood proteins on apoptotic cells and their impact on efferocytosis is a NIGMS - National Institute of General Medical Sciences grant providing up to $389K for university, nonprofit, healthcare org. Applications are due 2030-01-31 (open). Check eligibility and apply with FindGrants.
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Up to $389K
2030-01-31
- 1Confirm your organization is eligible for Defining the PS neighborhood proteins on apoptotic cells and their impact on efferocytosis from NIGMS - National Institute of General Medical Sciences, 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.
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Defining the PS neighborhood proteins on apoptotic cells and their impact on efferocytosis: Frequently Asked Questions
Who is eligible for the Defining the PS neighborhood proteins on apoptotic cells and their impact on efferocytosis?
Defining the PS neighborhood proteins on apoptotic cells and their impact on efferocytosis is offered by NIGMS - National Institute of General Medical Sciences 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 Defining the PS neighborhood proteins on apoptotic cells and their impact on efferocytosis provide?
Defining the PS neighborhood proteins on apoptotic cells and their impact on efferocytosis provides up to $389K per award from NIGMS - National Institute of General Medical Sciences. 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 Defining the PS neighborhood proteins on apoptotic cells and their impact on efferocytosis deadline?
Applications for Defining the PS neighborhood proteins on apoptotic cells and their impact on efferocytosis are due 2030-01-31 (open). Because deadlines can change, verify the date with the funder, NIGMS - National Institute of General Medical Sciences, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Defining the PS neighborhood proteins on apoptotic cells and their impact on efferocytosis?
To apply for Defining the PS neighborhood proteins on apoptotic cells and their impact on efferocytosis, 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 NIGMS - National Institute of General Medical Sciences.