Identifying arginylation inhibitors to attenuate injury-induced neuronal cell death
NINDS - National Institute of Neurological Disorders and Stroke
About This Grant
Attenuating neuronal cell death during the secondary phase of spinal cord injury (SCI) is critical for reducing long-term neurological dysfunction. Recent studies have identified protein arginylation—a posttranslational modification mediated by arginyltransferase 1 (ATE1), as a key driver of neuronal death following SCI. While genetic or pharmacologic suppression of ATE1 confers neuroprotection in both cellular and animal models, the lack of potent, specific, and in vivo-compatible small-molecule ATE1 modulators has hindered progress toward therapeutic development. Building on our prior work in ATE1 biology and assay development, we have established a novel dual- fluorescence, cell-based reporter platform capable of monitoring ATE1 activity in live cells with high sensitivity and compatibility for high-throughput screening (HTS). In this project, we aim to optimize this platform for large- scale compound screening at the R61 phase, and apply it to a ~645,000-compound small-molecule library to identify candidate ATE1 inhibitors at the R33 phase. Lead compounds will be validated through orthogonal biochemical assays, binding specificity studies, and pharmacologic profiling in SCI-relevant cell models, including mouse and human motor neurons. Our goal is to identify small-molecule ATE1 inhibitors with favorable drug-like properties that can serve as lead candidates for therapeutic intervention in SCI, first in animal models and ultimately in human patients. Our multi-PI team brings a unique and complementary set of expertise to this effort. The contact PI, Dr. Fangliang Zhang, a recognized leader in the ATE1/arginylation field, will lead assay development and validation. The multi-PI, Dr. Timothy Spicer, supported by co-investigators Drs. Louis Scampavia and Michael Cameron, brings extensive expertise in HTS and medicinal chemistry. Dr. Aaron Smith will contribute to protein characterization, while Dr. Mousumi Ghosh, an expert in neuronal models and SCI pathophysiology, will lead the pharmacologic evaluation of lead compounds. Together, this interdisciplinary team is well-positioned to advance the discovery of the first pharmacologically viable ATE1 modulators for the treatment of SCI.
Grant Summary
Identifying arginylation inhibitors to attenuate injury-induced neuronal cell death is a NINDS - National Institute of Neurological Disorders and Stroke grant providing up to $369K for university, nonprofit, healthcare org. Applications are due 2027-05-31 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $369K
2027-05-31
- 1Confirm your organization is eligible for Identifying arginylation inhibitors to attenuate injury-induced neuronal cell death from NINDS - National Institute of Neurological Disorders and Stroke, 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 NINDS - National Institute of Neurological Disorders and Stroke before the deadline.
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Identifying arginylation inhibitors to attenuate injury-induced neuronal cell death: Frequently Asked Questions
Who is eligible for the Identifying arginylation inhibitors to attenuate injury-induced neuronal cell death?
Identifying arginylation inhibitors to attenuate injury-induced neuronal cell death is offered by NINDS - National Institute of Neurological Disorders and Stroke 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 Identifying arginylation inhibitors to attenuate injury-induced neuronal cell death provide?
Identifying arginylation inhibitors to attenuate injury-induced neuronal cell death provides up to $369K per award from NINDS - National Institute of Neurological Disorders and Stroke. 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 Identifying arginylation inhibitors to attenuate injury-induced neuronal cell death deadline?
Applications for Identifying arginylation inhibitors to attenuate injury-induced neuronal cell death are due 2027-05-31 (open). Because deadlines can change, verify the date with the funder, NINDS - National Institute of Neurological Disorders and Stroke, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Identifying arginylation inhibitors to attenuate injury-induced neuronal cell death?
To apply for Identifying arginylation inhibitors to attenuate injury-induced neuronal cell death, 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 NINDS - National Institute of Neurological Disorders and Stroke.