Mapping MicroRNA-target Interactions in the Zonated Liver
NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases
About This Grant
ABSTRACT The lens of metabolic zonation is extremely pertinent to liver pathophysiology, and can be applied to both acute and chronic/progressive conditions like acute liver damage and MASLD/MASH. The long term goal is to better understand the role of microRNAs in liver physiology, microRNA dysregulation in pathophysiology, and to improve clinical outcomes for patients with acute and chronic liver diseases. The overall objective of this application is to unravel the specific mechanism by which microRNAs maintain metabolic zonation by mapping and validating microRNA-target interactions across the lobule with high fidelity to identify new biomarkers and inform therapeutics in the context of the healthy and diseased liver. The central hypothesis is that the phenomenon of metabolic zonation is at least partially controlled by miRNA-target networks that can be taken advantage of both therapeutically and diagnostically. The central hypothesis will be tested by pursuing two specific aims: 1) Mapping and validation of miRNA-target interactions in liver cells along the lobular axis with high fidelity and 2) Assessing dysregulation of miRNA-target networks in a model of acute and chronic liver disease. Under the first aim, we will use Spy3-Ago2-pulldown and sequencing (SAPseq) in mice with a Cre-inducible Spy3-tag on microRNA effector protein Ago2 (Cre +iSpy mice) to create a single high-fidelity map of differential miRNA-target regulation in spatially sorted hepatocytes, validate miRNA zonation using miRNA-sensing reporter constructs and independently validate node-level and global miRNA-target interactions using N-acetylgalactosamine conjugated miRNA sponging ASOs and vectors that deliver miRNA-blocking peptide ddT6B. For the second aim, we will use spatial sorting and SAPseq to evaluate miRNA-target changes in response to pericentral toxin APAP and periportal toxin allyl alcohol over time in Cre+ iSpy mice, miRNA-target changes in Cre+ iSpy mice fed a choline-deficient, L-amino acid defined, high fat diet over time (induces MASLD/MASH), and use serum SAPseq to evaluate circulating miRNA changes in both conditions. Our proposal is innovative as it utilizes technical advances in microRNA biology and Ago2 structure to expand our understanding of liver physiology with applications in addressing pathologies. Ultimately, this work will have a significant, direct, and positive impact in improving treatment options for patients with chronic liver diseases and diagnostics for acute liver diseases. Beyond the liver, it will have wide-reaching effects in the fields of cell, gene, and immunotherapy. The proposed work will be conducted at The Scripps Research Institute, under guidance of mentors in RNA biology, liver biochemistry, and clinical care. This proposal will be vital to supplement my dual-degree training to become an independent physician-scientist and domain expert in clinical RNA biology.
Grant Summary
Mapping MicroRNA-target Interactions in the Zonated Liver is a NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases grant providing up to $37K for university, nonprofit, healthcare org. Applications are due 2030-04-30 (open). Check eligibility and apply with FindGrants.
Focus Areas
Eligibility
How to Apply
Up to $37K
2030-04-30
- 1Confirm your organization is eligible for Mapping MicroRNA-target Interactions in the Zonated Liver 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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Mapping MicroRNA-target Interactions in the Zonated Liver: Frequently Asked Questions
Who is eligible for the Mapping MicroRNA-target Interactions in the Zonated Liver?
Mapping MicroRNA-target Interactions in the Zonated Liver 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 Mapping MicroRNA-target Interactions in the Zonated Liver provide?
Mapping MicroRNA-target Interactions in the Zonated Liver provides up to $37K 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 Mapping MicroRNA-target Interactions in the Zonated Liver deadline?
Applications for Mapping MicroRNA-target Interactions in the Zonated Liver are due 2030-04-30 (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 Mapping MicroRNA-target Interactions in the Zonated Liver?
To apply for Mapping MicroRNA-target Interactions in the Zonated Liver, 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.