Conformational mechanisms underlying allosteric regulation of the human serotonin transporter
NIMH - National Institute of Mental Health
About This Grant
PROJECT SUMMARY The human serotonin transporter (hSERT) plays a critical role in regulating serotonin (5-HT) signaling across nearly all major systems in the body. Dysregulation of hSERT is linked to numerous psychiatric and gastrointestinal disorders, making hSERT a primary target for clinical therapeutics including selective serotonin reuptake inhibitors (SSRIs). While the core ion-coupled transport cycle of hSERT is well characterized, the allosteric mechanisms that fine-tune its activity to meet diverse physiological demands remain poorly understood. This proposal aims to define the structural mechanisms by which 5-HT and the microbial metabolite butyrate allosterically shape hSERT’s conformational landscape to modulate its function. Aim 1 will leverage innovative cryo-EM approaches capable of resolving the full range of conformational states that define hSERT’s transport cycle, enabling the distinct structural effects of ligand binding at the central (S1) and allosteric (S2) substrate- binding sites to be isolated and characterized. These conformational changes will be directly linked to transport activity using complementary 5-HT uptake and electrophysiological assays. Aim 2 will expand our understanding of hSERT allosteric regulation by identifying the binding site of butyrate, characterizing its effects on hSERT’s conformational equilibrium, and determining its impact on transport activity. The training plan outlined in this fellowship is designed to strengthen technical and conceptual expertise in membrane protein biochemistry, single-particle cryo-EM, and electrophysiology. Mentorship and training from Dr. Eric Gouaux, an internationally recognized leader in membrane protein structural biology, and Dr. Michael Kavanaugh, an expert in transporter electrophysiology, will ensure the successful completion of the proposed aims. Together, these studies will advance the fundamental understanding of hSERT regulation and contribute to a broader framework for understanding allosteric modulation in neurotransmitter transporters, informing the development of innovative therapeutic strategies for disorders involving transporter dysfunction.
Grant Summary
Conformational mechanisms underlying allosteric regulation of the human serotonin transporter is a NIMH - National Institute of Mental Health grant providing up to $76K for university, nonprofit, healthcare org. Applications are due 2029-02-28 (open). Check eligibility and apply with FindGrants.
Focus Areas
Eligibility
How to Apply
Up to $76K
2029-02-28
- 1Confirm your organization is eligible for Conformational mechanisms underlying allosteric regulation of the human serotonin transporter from NIMH - National Institute of Mental Health, 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 NIMH - National Institute of Mental Health before the deadline.
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Conformational mechanisms underlying allosteric regulation of the human serotonin transporter: Frequently Asked Questions
Who is eligible for the Conformational mechanisms underlying allosteric regulation of the human serotonin transporter?
Conformational mechanisms underlying allosteric regulation of the human serotonin transporter is offered by NIMH - National Institute of Mental Health 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 Conformational mechanisms underlying allosteric regulation of the human serotonin transporter provide?
Conformational mechanisms underlying allosteric regulation of the human serotonin transporter provides up to $76K per award from NIMH - National Institute of Mental Health. 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 Conformational mechanisms underlying allosteric regulation of the human serotonin transporter deadline?
Applications for Conformational mechanisms underlying allosteric regulation of the human serotonin transporter are due 2029-02-28 (open). Because deadlines can change, verify the date with the funder, NIMH - National Institute of Mental Health, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Conformational mechanisms underlying allosteric regulation of the human serotonin transporter?
To apply for Conformational mechanisms underlying allosteric regulation of the human serotonin transporter, 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 NIMH - National Institute of Mental Health.