Team:UNC-Chapel Hill/Background

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BACKGROUND

Diabetes Diabetes is the inability of the body to properly uptake glucose into its cells. Usually occurs either because the body no longer generates adequate amounts of insulin in the islets of Langerhans, which will lead to a deficiency, or the body becomes resistant, reducing the effectiveness. As a result frequent insulin injection is a method of treatment. However this requires constant blood glucose level monitoring, which is costly and inconvenient. In the National Diabetes Statistics Report of 2014 released by the National Center for Chronic Disease Prevention and Health Promotion it was reported that 29.1 million Americans (9.3% of the US population) have diabetes mellitus. The cost both direct and indirect of diabetes treatment is estimated to be 245 billion dollars, and the disease remains the 7th leading cause of premature death in the United States. MLC (Makes Large Colonies) Our iGEM project aims to introduce a novel glucose sensing system in which glucose-responsive promoters drive the expression of three reporter chromoproteins. Using inspiration from a previous iGEM team, we designed four novel glucose-inducible promoters called MLC’s (makes large colonies). MLC is encoded by the gene dgsA, and is a repressor regulator of many phosphoenolpyruvate-dependent carbohydrate phosphotransferase systems (PTSs). These are pathways for carbohydrate uptake (glucose). Mlc binds directly to palindromic DNA sequences and blocks RNA polymerase from proceeding with transcription. In E. coli, Mlc specifically regulates the gene pstG, which encodes for the transmembrane glucose permease also called enzyme IICBGlu (regulation also involves a CRP binding site). The protein Mlc has high intracellular concentration when glucose concentration is low, and as a result, a promoter with Mlc binding sites would function as a glucose inducible promoter..

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