Type 1 diabetes mellitus (T1D) is a common autoimmune disease in children and results from autoimmune destruction of insulin-producing pancreatic ?-cells triggered by complex interactions of environmental factors and the immune system in genetically predisposed individuals. Although significant progress has been made in identification of both genetic risk and islet autoantibodies in disease prediction, the etiology of this disease remains unclear. High throughput technologies that provide comprehensive coverage of biomolecules can provide better understanding of the mechanisms behind developing islet autoimmunity and progression to T1D disease states. Proteomics approaches in particular can provide insight into the underlying pathways and protein networks involved, as well as identify peptides and proteins that may be utilized as predictive or diagnostic markers of developing disease.
The Environmental Determinants of Diabetes in the Young (TEDDY) is a consortium of investigators aiming to identify environmental factors that trigger the development of islet autoimmunity and T1D in genetically susceptible individuals. Children enrolled in TEDDY are at risk for T1D and have been prospectively followed with appropriate sampling at frequent intervals from birth up to the age of 9 (currently) and eventually up to the age of 15. This provides an ideal sample set for identifying signaling pathways or protein networks that are associated with developing disease and for testing the hypothesis that some of our previously reported peptide/protein markers might be linked with developing islet autoimmunity or with progression to T1D.
We propose to broadly identify and validate protein markers of developing autoimmunity as well as progression to T1D. In addition, we will provide basic proteomics support to the members of the TEDDY consortium by conducting GLP-like mass spectrometric analyses of peptide and protein abundances, and sharing these datasets with the TEDDY consortium through the TEDDY Data Coordinating Center. This will be achieved by leveraging our expertise in quantitative proteomics analyses, robust statistical analysis, and T1D biomarker discovery and validation.
Proteomics Laboratory for The Environmental Determinants of Diabetes in the Young
Science Theme:
Capabilities:
Lead Institution:
Pacific Northwest National Laboratory
Principal Investigator:
Thomas Metz
Project ID:
49637
Abstract: