Immunogenetics in the viral etiology and pathogenesis of type 1 diabetes
NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases
About This Grant
PROJECT SUMMARY Type 1 diabetes (T1D) results from a misdirected immune response, and its incidence has been increasing globally for decades. Viral infection, particularly with enterovirus, is a leading candidate trigger for the initiation and progression of islet cell destruction that ultimately results in clinical disease. Evidence from cell, mice, and human studies support this hypothesis, however, the findings from natural history studies of children at-risk for T1D are inconsistent. We posit that genetic variability contributes to this heterogeneity. Infection susceptibility and resolution depend heavily on first-line immune defenses by natural killer (NK) cells and the complement system, both of which are increasingly implicated in T1D pathogenesis and bridge innate and adaptive immune responses. Genetic variability within the killer cell immunoglobulin-like receptor (KIR) and major histocompatibility complex (MHC) loci directly affects these immune functions. Our overall hypothesis, supported by our preliminary data, is that combinatorial genetic variation controlling NK cell and/or complement system activity determines the course by which viral infection may contribute to the initiation of persistent islet autoimmunity (IA) and/or progression from IA to T1D. The genetic effects of these loci in a possible viral etiology and pathogenesis of T1D have been understudied, likely because they reside in highly complex genomic regions that are measured at insufficient resolution using common technologies. We propose to overcome this measurement problem by performing targeted, high-resolution sequencing of the 5Mbp MHC and 250kbp KIR regions with our novel cost-effective, high-throughput methods for >2,900 at-risk children being followed prospectively for the development of IA and T1D in two independent cohorts: The Environmental Determinants of Diabetes in the Young (TEDDY) study and the Diabetes Autoimmunity Study in the Young (DAISY). We will integrate this new sequence data with existing array data to catalog structural, polymorphic, and functional immunogenetic variation using proven bioinformatic algorithms for measuring NK cell and extended complement system activation potential (Aim 1). This unprecedented, high-resolution immunogenetic catalog enables novel exploration of NK cell and complement system contributions to susceptibility and response to a viral infection (Aim 2), and to risk for developing IA or T1D (Aim 3). These hypotheses can uniquely be tested within TEDDY, which has unparalleled precise and frequent virus exposure assessment and offers large enough sample size to detect phase-specific associations between genetic variation, infectious episodes, and T1D endpoints. With our requested minimal, low-priority sample expenditure, we can deliver high-impact findings of the immunogenetics underlying the natural history of T1D. Elucidating the genetic factors that confer susceptibility to persistent viral infections leading to IA and/or T1D progression may identify mechanisms to target for therapeutic development and, critically, will inform the structure of ongoing vaccine and antiviral T1D prevention trials.
Grant Summary
Immunogenetics in the viral etiology and pathogenesis of type 1 diabetes is a NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases grant providing up to $797K for university, nonprofit, healthcare org. Applications are due 2029-03-31 (open). Check eligibility and apply with FindGrants.
Focus Areas
Eligibility
How to Apply
Up to $797K
2029-03-31
- 1Confirm your organization is eligible for Immunogenetics in the viral etiology and pathogenesis of type 1 diabetes 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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Immunogenetics in the viral etiology and pathogenesis of type 1 diabetes: Frequently Asked Questions
Who is eligible for the Immunogenetics in the viral etiology and pathogenesis of type 1 diabetes?
Immunogenetics in the viral etiology and pathogenesis of type 1 diabetes 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 Immunogenetics in the viral etiology and pathogenesis of type 1 diabetes provide?
Immunogenetics in the viral etiology and pathogenesis of type 1 diabetes provides up to $797K 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 Immunogenetics in the viral etiology and pathogenesis of type 1 diabetes deadline?
Applications for Immunogenetics in the viral etiology and pathogenesis of type 1 diabetes are due 2029-03-31 (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 Immunogenetics in the viral etiology and pathogenesis of type 1 diabetes?
To apply for Immunogenetics in the viral etiology and pathogenesis of type 1 diabetes, 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.