EXPLOITING MICROBIOME SEQUENCES FOR IMPROVED MODELS OF PROTEIN-DNA INTERACTIONS

描述（由申请人提供）：该项目将开发计算机程序，利用人类微生物组计划（HMP）的DNA序列，以更好地了解DNA-蛋白质相互作用。转录因子和它们结合的DNA位点之间的相互作用对于控制每个物种内的基因表达至关重要，因此也是每个物种的特征及其与人类宿主的相互作用。转录因子本身可以很容易地从DNA序列中鉴定出来，我们将利用大多数细菌转录因子调节自身和/或其染色体内相邻基因的事实。基于来自研究充分的细菌的类似蛋白质的已知结构，转录因子可以被聚类成预期识别相同DNA模式的组。具有非常相似特异性的蛋白质簇和附近启动子的可能调控区一起将为我们提供大量潜在的DNA-蛋白质相互作用位点，在这些位点上应用模式发现算法。这不仅可以帮助我们了解HMP物种内的调控网络，而且还可以更全面地了解转录因子蛋白质与它们识别的DNA模式之间的关系。这将对生物学研究的几个领域产生更广泛的影响，并可能导致设计具有新特异性的新蛋白质，这些蛋白质可能用作研究工具和治疗方法。 公共卫生相关性：人类微生物组项目将从居住在人体许多不同微环境中的许多不同物种中获得DNA序列。该项目将开发计算机程序来分析这些DNA序列，以帮助发现这些物种的基因表达是如何调节的。基因表达的调控是理解微生物群落与人类宿主之间相互作用的关键因素。

DESCRIPTION (provided by applicant): This project will develop computer programs to exploit the Human Microbiome Project (HMP) DNA sequences to better understand DNA-protein interactions. The interactions between transcription factors and the DNA sites that they bind to are critical to controlling the expression of the genes within each species, and therefore also the characteristics of each species and its interactions with the human host. The transcription factors themselves can be readily identified from DNA sequences and we will take advantage of the fact that most bacterial transcription factors regulate themselves and/or adjacent genes within their chromosomes. Transcription factors can be clustered into groups that are expected to recognize the same patterns of DNA, based on known structures for similar proteins from well studied bacteria. Together the clusters of proteins with very similar specificity and the probable regulatory regions of nearby promoters will give us a very large number of potential DNA-protein interacting sites on which to apply pattern discovery algorithms. This should not only help us to learn about the regulatory networks within the HMP species, but also lead to more general understanding about the relationships between transcription factor proteins and the DNA patterns that they recognize. This will have broader implications across several areas of biological research and may lead to the design of new proteins with novel specificities that could be useful as research tools and for therapeutics. PUBLIC HEALTH RELEVANCE: The Human Microbiome Project will obtain DNA sequences from many different species inhabiting many different microenvironments of the human body. This project will develop computer programs to analyze those DNA sequences to help discover how the expression of the genes in those species is regulated. The regulation of gene expression is a key element in understanding the interactions between the microbial communities and the human host.