Annotating the Cis-Regulatory Binding Sites in Sequenced Prokaryotic Genomes

北卡罗来纳大学夏洛特分校获得了一笔赠款，用于开发软件和数据库资源，用于表征测序细菌中的顺式调控结合位点。细菌细胞的生物学功能是由细胞内基因(蛋白质和RNA)的产物来实现的，但这些蛋白质和RNA在不同的生理和环境条件下何时、何地、多大程度和多快地表达，主要受特定转录因子蛋白与染色体上基因上游顺式调控结合位点的相互作用控制。从总体上更好地了解原核生物对于全球生态控制、高效农业、更好的医药和健康以及可再生能源生产具有重要意义。然而，由于缺乏有效和准确的实验和计算方法来表征它们，我们对大多数已测序细菌基因组中的顺式调控系统的总体了解非常有限。该项目的研究团队将开发：1)一种新的工具，用于更准确地预测细菌中的操纵子，因为操纵子是细菌中的基本转录单位，了解基因组中的操纵子结构有助于预测其顺式调节结合位点。2)在全基因组范围内预测细菌顺式调节结合位点的有效和准确的工具。3)存储所有已测序细菌基因组中预测的操纵子和顺式调节结合位点的数据库系统。此外，这些预测工具的结果将通过对大肠杆菌K12中预测的大部分新的顺式调控位点的实验验证来验证和进一步完善。这些软件、数据库和实验程序将免费向公众开放，因此研究人员可以1)将该软件直接应用于他们感兴趣的基因组；2)在描述某些基因组中的顺式调控系统时，使用这些数据库进行靶标选择、实验设计和测试假说；以及3)使用实验程序来验证预测的顺式调控结合位点，同时识别同源转录因子。因此，这些工具和数据库将从根本上改变生物学家研究细菌顺式调控系统的方式。该项目还将提供一个独特的教育平台来培养下一代计算生物学家，一个博士后研究员，三个博士毕业生，以及不同数量的本科生和高中生将在该项目中接受培训。将特别鼓励传统上代表人数较少的少数族裔和/或女性学生参与该项目。此外，这个项目产生的算法和结果将被纳入北卡罗来纳大学夏洛特分校新开发的首席研究员S的课程中。有关该项目的更多信息可在http://gleclubs.uncc.edu/pbs上找到，有关研究小组的信息可在http://sulab.uncc.edu.上找到。

"This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)."University of North Carolina at Charlotte has been awarded a grant to develop software and a database resource for characterizing cis-regulatory binding sites in sequenced bacteria. Biological functions of a bacterial cell are carried out by the products of genes (proteins and RNAs) in the cell, but when, where, how much and how fast these proteins and RNAs should be expressed under different physiological and environmental conditions are mainly controlled by the interactions between specific transcription factor proteins and the cis-regulatory binding sites in the upstream regions of the genes on the chromosome. A better understanding of prokaryotes in general has great significance in global ecological control, efficient agriculture, better medicine and health, and renewable energy production. However, our general understanding of cis-regulatory systems in most sequenced bacterial genomes is very limited due to the lack of efficient and accurate experimental and computational methods for their characterization. The research team of this project will develop: 1) A new tool for more accurate prediction of operons in bacteria, since operons are the basic transcription units in bacteria and knowing operon structures in a genome can facilitate its cis-regulatory binding site prediction. 2) An efficient and accurate tool for genome-wide prediction of cis-regulatory binding sites in bacteria.3) A database system to store the predicted operons and cis-regulatory binding sites in all sequenced bacteria genomes. In addition, the results of these prediction tools will be verified and further refined through experimental validation of a large portion of the predicted novel cis-regulatory sites in E. coli K12. These software, database and experimental procedures will be freely available to the public, thus researchers can 1) directly apply the software to their genomes of interest; 2) use the database for target selection, experimental design and testing hypotheses when characterizing cis-regulatory systems in certain genomes; and 3) use the experimental procedures to verify the predicted cis-regulatory binding sites, and at the same time, identify the cognate transcription factors. Therefore, these tools and database will fundamentally change the way that biologists study cis-regulatory systems in bacteria. This project will also provide a unique educational platform to train the next generation of computational biologists, as one postdoctoral fellow, three PhD graduates, and various numbers of undergraduates and high school students will be trained in the project. Traditionally underrepresented minority and/or female students will be particularly encouraged to participate in the project. Furthermore, the algorithms and results generated from this project will be incorporated into the principle investigator?s newly developed courses at the University of North Carolina at Charlotte. More information about the project can be found at http://gleclubs.uncc.edu/pbs and information about the research team can be found at http://sulab.uncc.edu.