Team:Duke

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Abstract

Medical genetic therapy has shown promise for improved accuracy in personalized genetic therapy of conditions such as Alzheimer’s disease and cancer. However, the speed of current medical genetic screening methods is limited by time-consuming rates of cell growth and gene expression. The goal of this work, therefore, was to develop a comprehensive platform for other researchers to use in further medical genetic studies. In yeast, an orthologous model of human gene function, we developed a system of two dimerizing fusion proteins to control two-hybrid mediated transcriptional activation in response to a 450 nm blue light (optogenetic) stimulus. After extensive characterization and optimization of our system, we compiled our methodologies into a physical toolkit, which contains custom yeast strains frozen in glycerol stocks, standardized plasmids, a stochastic network model, the design of a light pulse generator to induce gene expression, and a custom software package for rapid analysis of data. In the coming weeks, we will begin testing an application of our system by screening for orthologous suppressors of beta-amyloid that may be used in genetic therapy of Alzheimer’s disease. Our comprehensive toolkit streamlines identification of genetic therapeutic targets, and will speed progress toward personalized therapy of a variety of diseases.