Contribution of alternative splicing in beta cells to the etiology of Type 1 Diabetes
EMSL Project ID
60146
Abstract
This proposal covers work done under an NIH-funded project led by the University of Colorado. Type 1 diabetes mellitus (T1D) is a chronic disease resulting from the autoimmune destruction of insulin-producing pancreatic beta cells. Although T1D is primarily associated with a dysfunctional immune response, recent genome-wide association studies (GWAS) have determined that a large number of T1D associated genes are expressed in pancreatic beta cells. Correspondingly, there is evidence that beta cell dysfunction occurs early in the T1D disease process and may contribute to and/or exacerbate the autoimmune response. This is supported by the discovery of novel hybrid peptides and post-translational modifications within beta cells that contribute to the disease by triggering autoreactive T cells. Currently, there are many ongoing studies to identify the underlying molecular mechanisms that impact beta cell dysfunction in T1D, with hopes that this knowledge can be used to develop novel biomarkers and preventive disease therapies. We hypothesize that altered alternative splicing of RNA contributes to beta cell dysfunction and possibly to the formation of potentially immunogenic protein isoforms in T1D. To test this hypothesis, the study has been using multiple approaches. This EMSL Staff proposal focuses on identifying the molecular characteristics (RNA localization and RNA modifications) of candidate RNA isoforms in individual islet cells using fliFISH in human islet tissue sections and determine the functional ramifications of expressing alternatively spliced products in beta cells.
Project Details
Start Date
2021-06-11
End Date
2023-10-01
Status
Closed
Released Data Link
Team
Principal Investigator