PostDoctoral Research Fellowship in Biological Informatics FY2006

项目名称：“破坏基因调控的突变会增加细菌和数字生物的进化创造力吗？”本课题为2006年度生物信息学博士后科研资助项目。这项研究将检验人们普遍持有的观点，即在达尔文系统中存在一种权衡，即不断增加的可进化性（适应性突变的频率）会降低稳健性（随机突变产生可存活生物体的可能性）。具体来说，该研究员将测试破坏细菌和数字生物中现有基因调控网络的靶向突变是否会使它们更容易进化，更不健壮。为此，他将首先创建大肠杆菌变种，在这种变种中，他禁用了在生长不需要的条件下沉默某些基因的调节系统（例如碳分解代谢抑制和rho依赖性转录终止）。然后，他将在长期的实验室实验中比较正常细菌和突变细菌的进化能力，以利用190种不同的碳源。他将使用Avida软件程序进行类似的测试，使数字生物进化出感知环境奖励结构的能力，然后检查短路这种调节是否会以降低稳健性为代价导致更大的进化能力。总之，这些研究将提供对细菌中新化学多样性进化的进化途径的更好理解，并回答物种在一种条件下如何优化生长与在新环境下如何创造性地进化以茁壮成长之间是否存在紧张关系。该研究将在密歇根州立大学Richard Lenski和Charles Ofria的实验室进行，研究员将在那里学习细菌和数字生物实验，经典微生物学方法以及先进的高通量技术，如表型微阵列，DNA微阵列，代谢组学分析和polony基因组重测序。信息学培训将包括为Avida软件提供c++编程语言模块，以及使用计算集群分析大型数据集。这一培训将显著增强研究员目前在功能蛋白和核酸序列的试管进化方面的背景知识。

Project Title: "Do Mutations that Disrupt Gene Regulation Increase the Evolutionary Creativity of Bacteria and Digital Organisms?"This project is awarded under the Postdoctoral Research Fellowships in Biological Informatics Program for 2006. This research will test the commonly held belief that there is a tradeoff in Darwinian systems such that increasing evolvability (the frequency of adaptive mutations) decreases robustness (the likelihood that a random mutation will result in a viable organism). Specifically, the Fellow will test whether targeted mutations that disrupt existing gene regulation networks in bacteria and digital organisms make them more evolvable and less robust. To do this he will first create Escherichia coli variants where he has disabled regulatory systems that silence certain genes under conditions where they are not necessary for growth (e.g. carbon catabolite repression and Rho-dependent transcription termination). He will then compare the abilities of normal and mutant bacteria to evolve to utilize 190 different carbon sources in long-term laboratory experiments. He will perform analogous tests using the Avida software program enabling digital organisms to evolve the ability to sense the reward structures of their environments and then examine whether short-circuiting this regulation causes greater evolvability at the cost of decreased robustness. Together, these studies will provide a greater understanding of the evolutionary pathways by which new chemical diversity evolves in bacteria and answer whether there is a tension between how optimized a species is for growth under one condition and how readily it can creatively evolve to thrive under new circumstances.The research will be carried out at Michigan State University in the labs of Richard Lenski and Charles Ofria where the Fellow will learn experimentation with bacteria and digital organisms, classical microbiological methods, and advanced high-throughput technologies such as phenotype microarrays, DNA microarrays, metabolomics profiling, and polony genome resequencing. Informatics training will include contributing C++ programming language modules to the Avida software, and analysis of large datasets using computing clusters. This training will significantly enhance the Fellow's current background in the test tube evolution of functional protein and nucleic acid sequences.