CAREER: A Framework for Directed Genome Evolution

这项拟议的工作需要优化细菌E.Coli中的原生质体融合和基因组重组方法。此外，基因芯片将被用来识别与抗生素(AA-羟基甲酸酯)耐受表型有关的基因，小网络理论将被用来理解连接性和集群如何影响抗生素耐受性与适应性。提高对基因组进化的理解，以及个体代谢途径的产量与生物体适应性之间的权衡，有望对代谢工程界产生积极影响。这一影响源于对细胞系统如何在分子水平上管理“全局”与“局部”优化的更多见解。这样的洞察力反过来将允许改进对不同代谢工程策略结果的定量预测。更好地理解基因组进化如何导致抗生素耐药性和生物体适应性，也应该对应对抗生素耐药性细菌的医学问题产生积极影响。将研究纳入教育和宣传的计划有两个目标。首先，将通过工程、多元文化工程和高中荣誉计划开展外展活动。其次，本科生将被组织成小组，负责开发实验室演示模块。这样的团队将整合以前的课程工作，并在制作有用的课件的同时学习协作技能。

0449183Gill The proposed work entails optimizing protoplast fusion and genome-shuffling approaches in the bacterium, E. coli. Additionally, gene chips will be used to identify the genes responsible for antibiotic (aa-hydroxamate) tolerant phenotypes, and small network theory will be employed to understand how connectivity and clustering may affect antibiotic tolerance versus fitness. Improving the understanding of genome evolution and the tradeoffs between the yield from individual metabolic pathways and organism fitness is expected to make a positive impact on the metabolic engineering community. The impact follows from more insights being gleaned on how "global" versus "local" optimization is managed at the molecular level by cellular systems. Such insights, in turn, will allow for improved quantitative prediction of the outcome of different metabolic engineering strategies. Understanding better how genomic evolution can lead to antibiotic resistance and organism fitness should also positively impact work on contending with the medical problem of antibiotic resistant bacteria. The plan to integrate research into education and outreach has two objectives. First, outreach activities will be pursued via Women in Engineering, Multicultural Engineering, and high school honors programs. Secondly, undergraduates will be organized into teams that are charged with developing laboratory demonstration modules. Such teams will integrate prior coursework and learn collaboration skills while producing useful courseware.