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Biological Sciences

Advanced Proteomics and Metabolomics Studies of Type 1 Diabetes

Sponsor: National Institutes of Health
Contact: Tom Metz
Collaborators: Pat Mueller, Centers for Disease Control; Vincent Poitout, Pacific Northwest Research Institute

The term "metabolome" refers to the entire complement of all the small-molecular-weight metabolites and (generally small-molecule) related species at a given time for a system of interest. Quantitative metabolomic measurements that can cover a significant fraction of either or both the intracellular and extra-cellular metabolites are key to understanding metabolism and regulation of cellular systems, and complement gene expression and proteomic information. This coordination of genomic, proteomic and metabolomic information (also known as systems biology) can provide a more complete picture of the changes that take place within a biological system under varying conditions.

Type 1 diabetes mellitus is a chronic disease, affecting ~1 million individuals in the U.S. alone. It is caused by autoimmune destruction of the pancreatic beta cells, which results in loss of endogenous insulin productions and a lifetime regime of exogenous insulin therapy. Research in the field has centered on discovering novel biomarkers predictive of type 1 diabetes, its complications, and the efficacy of associated treatments. Our goal is to apply proteomic and metabolomic technologies to identify biomarkers predictive of both this type of diabetes and successful islet cell transplantation. More specifically, we are applying high-resolution nanoflow capillary LC-FTICR analyses combined with the AMT tag approach to study plasma/serum from recently diagnosed type 1 diabetes patients and islet preparations to identify novel proteomic and metabolomic biomarkers for type 1 diabetes and islet cell performance in vivo, respectively.

This project involves optimizing sample processing and LC conditions to maximize metabolomic coverage of human control/diabetic plasma and serum; comparative studies to determine proteomic and metabolomic differences of plasma versus serum and fasting versus non fasting states; developing mass and time tag databases of both plasma/serum proteins and metabolites from both fasting and non-fasting samples; and performing a pilot study to define specific differences in the proteome and metabolome of samples from healthy control and newly diagnosed type 1 diabetic patients.

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