Elucidating the Human Beta Cell Translatome in Health and Disease
Contact PI: Holger Russ, PhD, University of Florida
Start Date: June 1, 2018
End Date: June 30, 2023
HIRN New Investigator Award Recipient
Abstract
Type 1 diabetes (T1D), the immune mediated form of diabetes, results from an erroneous attack of the patients own immune system on pancreatic beta cells. Despite decades of research efforts, we still do not know why and how T1D develops in patients. Recent studies provide first novel insights into a potentially critical missing link in disease pathogenesis: namely pancreatic beta cells produce aberrant translational products leading to ‘diabetogenic’ peptides that induce an autoimmune attack towards dysfunctional beta cells. Here, I propose to comprehensively address the global production of such `diabetogenic` products by employing ribosomal profiling approaches to define start codon usage and mRNA translation in human beta cells in steady-state conditions and under stress. These studies will be essential for understanding the mechanisms underlying the production of non-canonical proteins/peptides, for which no central tolerance exist. Our innovative approach has the potential to lead to break-through(s) in our understanding of the progression of T1D and thus provide critical novel knowledge how to treat and/or prevent autoimmune T1D from (re-)occurring.
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