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

细胞通常执行复杂的计算任务，使它们能够控制数千个基因的编排，并与其他细胞进行通信，以表现出诸如生长和分化等新的特性。理解和设计细胞复杂计算机制的算法应该对科学和技术，特别是生物技术产生重大影响，生物计算和医学。最近几个值得注意的报道表明，在大肠杆菌中设计和构建简单的从头遗传电路是可能的，例如开关和振荡器。这项工作还表明，即使是最简单的体内电路的实现也需要对蛋白质-DNA相互作用以及mRNA和蛋白质稳定性等参数进行繁琐的优化。我们建议开发高效，构建功能性从头遗传电路的进化设计策略。我们将把分子进化的方法应用于复杂的遗传系统，包括多个阻遏物、操纵子和启动子。我们相信，进化将被证明普遍适用于优化单个装置以及复杂的遗传电路，我们的目标是展示进化搜索是如何最好地进行的，以便建立设备库并将其组装成功能电路。

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.