Allosteric Mechanisms and Regulation of Drp1-catalyzed Mitochondrial Fission
About This Grant
PROJECT SUMMARY Mitochondria are dynamic organelles that undergo cycles of division and fusion. Mitochondrial division (MD) is essential for mitochondrial quality control, transport, distribution, and inheritance. Defects in MD underlie various neurological disorders, including Alzheimer’s, Parkinson’s, and Huntington’s diseases, as well as cardiovascular disease and cancer. While the mechanochemical GTPase dynamin-related protein 1 (Drp1) is key to MD, the molecular mechanisms governing Drp1 function in mitochondrial membrane remodeling remain poorly understood. Recent studies indicate that Drp1 is both structurally and functionally autoinhibited, necessitating an essential role for binding partners in alleviating this autoinhibition. Here, we will investigate the distinct allosteric nodes of functional control exercised by the protein partners GIPC1, MiD51, and Dynamin 2 (Dyn2) on Drp1-catalyzed MD. This grant application aims to address several unknown fundamental issues essential for understanding Drp1-catalyzed MD. These include: 1) understanding the structural basis and mechanism of autoinhibition by the intrinsically disordered Drp1 C-terminal Short Linear Motif, and its alleviation by GIPC1, 2) investigating the mechanisms involved in the MiD51-directed conformational transition of Drp1 from the autoinhibited form in solution to the assembly-competent form on membranes, including the role of the putative interface-4 in MiD51-directed Drp1 co-assembly, and 3) studying the mechanisms of Dyn2 in regulating Drp1 assembly-disassembly dynamics on membranes to improve membrane fission efficacy. We will combine mutagenesis and X-ray crystallography with cutting-edge cryo-EM, and multiple independent fluorescence spectroscopic and imaging techniques to address these aims. Successful outcomes of this research project will provide (i) a fundamentally improved understanding of the mechanisms underlying Drp1-catalyzed MD, and (ii) a molecular foundation for the design of drugs and therapeutics that can beneficially modulate MD in various diseased states.
Grant Summary
Allosteric Mechanisms and Regulation of Drp1-catalyzed Mitochondrial Fission is a NIGMS - National Institute of General Medical Sciences grant providing up to $461K for university, nonprofit, healthcare org. Applications are due 2030-03-31 (open). Check eligibility and apply with FindGrants.
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Up to $461K
2030-03-31
- 1Confirm your organization is eligible for Allosteric Mechanisms and Regulation of Drp1-catalyzed Mitochondrial Fission 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.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIGMS - National Institute of General Medical Sciences before the deadline.
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Allosteric Mechanisms and Regulation of Drp1-catalyzed Mitochondrial Fission: Frequently Asked Questions
Who is eligible for the Allosteric Mechanisms and Regulation of Drp1-catalyzed Mitochondrial Fission?
Allosteric Mechanisms and Regulation of Drp1-catalyzed Mitochondrial Fission 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 Allosteric Mechanisms and Regulation of Drp1-catalyzed Mitochondrial Fission provide?
Allosteric Mechanisms and Regulation of Drp1-catalyzed Mitochondrial Fission provides up to $461K 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 Allosteric Mechanisms and Regulation of Drp1-catalyzed Mitochondrial Fission deadline?
Applications for Allosteric Mechanisms and Regulation of Drp1-catalyzed Mitochondrial Fission are due 2030-03-31 (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 Allosteric Mechanisms and Regulation of Drp1-catalyzed Mitochondrial Fission?
To apply for Allosteric Mechanisms and Regulation of Drp1-catalyzed Mitochondrial Fission, 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.