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Fully understanding the genetic basis of both T1D and T2D requires a concerted, systematic effort to interpret in the laboratory the coding and non-coding variations associated with disease. Non-coding variants — which comprise more than 80 percent of variants associated with T2D — are particularly difficult to interpret, due to the cell type- and condition- specific nature of their activity. 

Teams of researchers within the Diabetes Initiative are developing and employing a wide range of cellular models, genomic editing methods, multi-omic readouts, imaging-based assays, computational/machine learning approaches, and animal models to learn how genetic variants influence cellular pathways and circuits, interactions among cells and between them and their environment, and physiological processes related to disease. In particular, BDI researchers and their collaborators are working to:

• Pinpoint causal genes and variants and the ways in which genetic variation disrupts gene and protein function
• Understand the signaling pathways that promote the growth, differentiation, and survival of pancreatic islet cells
• Molecularly assess cellular features, functions, and responses related to T2D and the effects of genetic variation on them
• Identify previously unrecognized cellular and physiological pathways and processes that influence the biological basis of disease and disease-related traits, as these could represent important therapeutic targets for those with or at risk for developing T2D
• Determine the mechanisms by which genetic variation governs responses to treatment
• Explore cellular processes that genetics suggests are associated with diabetes but for which the mechanisms are not yet clear