Biodiversity and Ecosystem Informatics - BDEI -Bioinformatic Prediction of Functions of Unculturable Microbes in Ecosystems

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EIA-0131899Dickerson, AllanVirginia Polytechnic Institute and State UniversitySUMMARYCells routinely perform complex computational tasks that enable them to control the orchestrationof thousands of genes and communicate with other cells to manifest emergent properties such as growthand differentiation.Understanding and engineering the algorithms underlying the complex computationalmachinery of cells should have significant impact in science and technology,particularly biotechnology,biocomputation and medicine.Several notable recent reports demonstrate that it is possible to design and construct simple denovo genetic circuits such as a switch and an oscillator in Escherichia coli .This work also revealed thatimplementation of even the most simple circuits in vivo requires tedious optimization of often poorly-understood protein-DNA interactions and mRNA and protein stabilities,among other parameters.Wepropose to develop efficient,evolutionary design strategies for constructing functional de novo geneticcircuits.We will apply methods of molecular evolution,which have proven highly successful forengineering proteins with improved or altered properties,to complex genetic systems involving multiplerepressors,operators,and promoters.We believe that evolution will prove to be generally applicable foroptimizing individual devices as well as complex genetic circuits,and our goal will be to demonstratehow evolutionary searches are best performed in order to build libraries of devices and assemble theminto functional circuits.