PostDoctoral Research Fellowship in Biological Informatics FY2006

项目标题：“破坏基因调控的突变是否增加了细菌和数字有机体的进化创造力？”该项目是根据2006年生物信息学博士后研究奖学金授予的。这项研究将检验一种普遍持有的信念，即达尔文系统中存在权衡，即不断增加的进化性(适应性突变的频率)会降低稳健性(随机突变将产生活的有机体的可能性)。具体地说，这位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定向突变是否会使它们更具进化性，更不健壮。要做到这一点，他将首先创建大肠杆菌变体，其中他已经禁用了调控系统，这些调控系统在某些对生长不必要的条件下使某些基因沉默(例如，碳分解代谢抑制和依赖于Rho的转录终止)。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利用190种不同碳源进化的能力。他将使用Avida软件程序进行类似的测试，使数字有机体能够进化出感知环境奖励结构的能力，然后研究是否短路这一规定会导致更大的进化性，代价是健壮性降低。总之，这些研究将提供对细菌中新的化学多样性进化途径的更多了解，并回答一个物种在某种条件下对生长的优化程度与它在新环境下创造性进化的难易程度之间是否存在紧张关系。这项研究将在密歇根州立大学理查德·伦斯基和查尔斯·奥弗里亚的实验室进行，在那里，这位研究员将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、代谢组学图谱和Polony基因组重测序。信息学培训将包括向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。这项培训将大大增强这位研究员目前在功能蛋白质和核酸序列的试管进化方面的背景。

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.