CAREER: A Framework for Directed Genome Evolution

0449183 Gill所提出的工作需要优化细菌E.杆菌 此外，基因芯片将用于识别负责抗生素（aa-异羟肟酸）耐受表型的基因，并将采用小网络理论来了解连接性和聚类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，预计将对代谢工程界产生积极影响。 这种影响来自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。 反过来，这样的见解将允许对不同代谢工程策略的结果进行改进的定量预测。更好地了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解决抗生素耐药性细菌的医学问题产生积极影响。 将研究纳入教育和外联的计划有两个目标。 首先，将通过妇女参与工程、多元文化工程和高中荣誉课程开展外联活动。 其次，本科生将被组织成负责开发实验室演示模块的团队。 这样的团队将整合以前的课程，学习协作技能，同时制作有用的课件。

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.