Unraveling Counter-Regulatory Transcriptional Control by the ZBED Family in Beta Cell Stress and Immune Tolerance
NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases
About This Grant
PROJECT SUMMARY Type 1 diabetes (T1D) results from immune-mediated destruction of pancreatic beta cells. Increasing evidence suggests that beta cells actively contribute to their own demise through heightened immunogenicity, stress-induced neoantigen formation, and impaired immune tolerance. Enhancing beta cell resilience under inflammatory conditions remains a major challenge to the success of durable therapies, especially for cell replacement approaches. Our in vivo CRISPR/Cas9 screen identified ZBED3 — a transcription factor previously implicated in type 2 diabetes (T2D) — as a modulator of beta cell survival under autoimmune attack. Analysis of human islet single-cell RNA sequencing data revealed increased ZBED3 expression in beta cell subclusters associated with both T1D and T2D, whereas ZBED2, a related transcription factor with anti-inflammatory properties, is selectively absent in beta cells. Integration of public ZBED2 chromatin immunoprecipitation sequencing (ChIP-seq) and our in-house ZBED3 ChIP-seq datasets identified shared transcriptional targets involved in interferon signaling, FOXO-mediated transcription, and beta cell function. These findings suggest that ZBED family members may exert opposing regulatory effects on beta cell fate during autoimmune diabetes. This proposal aims to elucidate the transcriptional mechanisms underlying beta cell vulnerability by testing the hypothesis that ZBED2 and ZBED3 govern the balance between beta cell function, immune tolerance, and stress adaptation. Using genetically engineered beta cells derived from human induced pluripotent stem cells (iPSCs) and primary islets, we will pursue two specific aims: Aim 1. Define the role of ZBED3 in regulating beta cell immunogenicity, functional maturation, and stress response. Aim 2. Enhance immune tolerance by inducing ZBED2 and investigating its antagonistic effects on inflammatory signaling. This study combines gene editing, transcriptomic profiling, and T cell cytotoxicity assays to elucidate regulatory pathways governing beta cell survival. By establishing ZBED2 and ZBED3 as central regulators of beta cell fate, this work addresses a critical gap in T1D therapy and supports the development of transcription-based strategies to improve the durability of cell replacement interventions.
Grant Summary
Unraveling Counter-Regulatory Transcriptional Control by the ZBED Family in Beta Cell Stress and Immune Tolerance is a NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases grant providing up to $150K for university, nonprofit, healthcare org. Applications are due 2028-06-30 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $150K
2028-06-30
- 1Confirm your organization is eligible for Unraveling Counter-Regulatory Transcriptional Control by the ZBED Family in Beta Cell Stress and Immune Tolerance 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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Unraveling Counter-Regulatory Transcriptional Control by the ZBED Family in Beta Cell Stress and Immune Tolerance: Frequently Asked Questions
Who is eligible for the Unraveling Counter-Regulatory Transcriptional Control by the ZBED Family in Beta Cell Stress and Immune Tolerance?
Unraveling Counter-Regulatory Transcriptional Control by the ZBED Family in Beta Cell Stress and Immune Tolerance 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 Unraveling Counter-Regulatory Transcriptional Control by the ZBED Family in Beta Cell Stress and Immune Tolerance provide?
Unraveling Counter-Regulatory Transcriptional Control by the ZBED Family in Beta Cell Stress and Immune Tolerance provides up to $150K 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 Unraveling Counter-Regulatory Transcriptional Control by the ZBED Family in Beta Cell Stress and Immune Tolerance deadline?
Applications for Unraveling Counter-Regulatory Transcriptional Control by the ZBED Family in Beta Cell Stress and Immune Tolerance are due 2028-06-30 (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 Unraveling Counter-Regulatory Transcriptional Control by the ZBED Family in Beta Cell Stress and Immune Tolerance?
To apply for Unraveling Counter-Regulatory Transcriptional Control by the ZBED Family in Beta Cell Stress and Immune Tolerance, 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.