Discovery of Early Type 1 Diabetes Disease Processes in the Human Pancreas [HIRN Consortium on Beta Cell Death and Survival (CBDS)] (U01 Clinical Trial Not Allowed)

Background
This Notice of Funding Opportunity (NOFO) requests applications to explore human pancreatic tissues and the immune compartment for the discovery of specific signaling or processing pathways that may contribute to the asymptomatic phase of T1D, the discovery of early biomarkers of T1D pathogenesis, the development of diagnostic tools for the detection and staging of early T1D in at-risk or recently-diagnosed individuals, and/or the identification and biological validation of therapeutic targets for the development of preventative or early treatment strategies. Successful applicants will join the Consortium on Beta Cell Death and Survival (CBDS), whose mission is to better define and detect the mechanisms of beta cell stress and destruction central to the development of T1D in humans, with the long-term goal of protecting the residual beta cell mass in T1D patients as early as possible in the disease process, and of preventing the progression to autoimmunity. The CBDS is part of a collaborative research framework, the Human Islet Research Network (HIRN), whose overall mission is to support innovative and collaborative translational research to understand how human beta cells are lost in T1D, and to find innovative strategies to protect and replace functional beta cell mass in humans. This NOFO will only support studies with a primary focus on increasing our understanding of human disease biology (as opposed to rodent or other animal models).

Grant Details
The initiative supports the exploration of human cells and tissues for the discovery of specific cellular dysfunctions and changes in the islet environment that contribute to the disappearance of pancreatic beta cells in patients with T1D, early biomarkers discovery, identification of therapeutic targets for preventative or early treatment strategies, exploration of adaptive or defensive mechanisms employed by human beta cells to survive in an increasingly hostile disease environment, identification events of cell dysfunction, stress, injury, plasticity or trafficking that take place in the human islet or its vicinity during the asymptomatic phase of T1D and may contribute to beta cell survival, islet inflammation or beta cell immunogenicity.

It also aims to describe impaired signaling or processing pathways contributing to islet inflammation or generation of neoepitopes; develop molecular tools; identify specific cell types within islet environment; identify modified or misprocessed cell products specific to a stressed islet niche; identify conditions making a beta cell turn immunogenic; perform deep molecular profiling of immune compartment; identify cell products released in circulation throughout life of beta cells; validate new biomarkers and diagnostic tools in clinical samples; identify adaptive changes in human beta cells exposed to immune assault; identify therapeutic targets in pathways contributing to disease initiation; explore cellular and molecular basis for heterogeneity of T1D etiology.

Eligibility Requirements
Eligible applicants include higher education institutions, nonprofits with 501(c)(3) IRS status, for-profit organizations including small businesses, state governments, county governments, city or township governments, special district governments, Indian/Native American Tribal Governments (Federally Recognized), U.S. Territory or Possession, independent school districts, public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), faith-based or community-based organizations. Foreign institutions are not eligible to apply directly but foreign components are allowed.

Period of Performance
The period of performance for this grant opportunity starts from July 9th 2024 with application due dates falling on November 2024. The maximum project period is 4 years.

Grant Value
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) intends to commit up to $3.5 million to fund 4-6 awards in FY 2024. Application budgets are limited to $550,000 in direct costs per year.