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, https://hirnetwork.org/), 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). This NOFO will not accept applications proposing a clinical trial.