C elegans-based screening of hyperglycemia-induced diabetic cell dysfunction
We propose to utilize an in vitro C elegans model of hyperglycemia-induced cell dysfunction and shortened life span, as a model to study the complications of Type 1 and Type 2 diabetes. Using this model we propose to conduct cell-based screening of (1) a library of clinically used drugs and drug-like small molecules and (2) a siRNA library. The goal is to generate proof-of-concept data to show that this approach can be utilized to identify small molecules and genes, which beneficially affect the survival of worms exposed to elevated extracellular glucose. The current approach represents an innovative novel approach for the identification of compounds and novel therapeutic targets that counteract the complications of diabetes. Specific Aim 1 is to conduct a pilot small molecule screening campaign of clinically used and pharmacologically active compounds to identify clinically used drugs that extend the life span in the hyperglycemic C elegans model of diabetic complications. Specific Aim 2 is to conduct a pilot siRNA screening campaign to identify pathways which extend life span in the hyperglycemic C elegans model of diabetic complications.

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