Towards a comprehensive protein interactome network in Schizosaccharomyces pombe

粟酒裂殖酵母全面的蛋白质相互作用组网络

• 批准号: 8461576
• 负责人: Haiyuan Yu
• 金额: $ 35.97万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8461576
• 关键词: Address; Affinity Chromatography; Animal Model; Architecture; Bioinformatics; Biological; Biological Assay; Biological Process; Biology; Cells; Centromere; Complement; Complex; Data; Data Set; Databases; Development; Disease; Ensure; Evolution; Exons; Fission Yeast; Gene Expression Regulation; Gene Proteins; Generations; Genes; Genome; Genomics; Goals; Heterochromatin; Histones; Individual; Introns; Knowledge; Literature; Mammalian Cell; Mammals; Maps; Mass Spectrum Analysis; Methodology; Methods; Methylation; Mitotic; Nature; Open Reading Frames; Organism; Pathway Analysis; Pathway interactions; Physiology; Process; Protein Analysis; Protein-Protein Interaction Map; Proteins; Proteome; Proteomics; RNA Interference; RNA Splicing; Regulation; Replication Origin; Research; Saccharomyces cerevisiae; Saccharomycetales; Schizosaccharomyces pombe Proteins; Science; Signal Pathway; Structure; Systems Biology; Technology; Telomere-Binding Proteins; Therapeutic; Time; Work; Yeasts; biological systems; comparative; cost; genome sequencing; improved; insight; network models; novel; predictive modeling; protein complex; protein function; protein protein interaction; public health relevance; research study; tool; yeast two hybrid system; Address; Affinity Chromatography; Animal Model; Architecture; Bioinformatics; Biological; Biological Assay; Biological Process; Biology; Cells; Centromere; Complement; Complex; Data; Data Set; Databases; Development; Disease; Ensure; Evolution; Exons; Fission Yeast; Gene Expression Regulation; Gene Proteins; Generations; Genes; Genome; Genomics; Goals; Heterochromatin; Histones; Individual; Introns; Knowledge; Literature; Mammalian Cell; Mammals; Maps; Mass Spectrum Analysis; Methodology; Methods; Methylation; Mitotic; Nature; Open Reading Frames; Organism; Pathway Analysis; Pathway interactions; Physiology; Process; Protein Analysis; Protein-Protein Interaction Map; Proteins; Proteome; Proteomics; RNA Interference; RNA Splicing; Regulation; Replication Origin; Research; Saccharomyces cerevisiae; Saccharomycetales; Schizosaccharomyces pombe Proteins; Science; Signal Pathway; Structure; Systems Biology; Technology; Telomere-Binding Proteins; Therapeutic; Time; Work; Yeasts; biological systems; comparative; cost; genome sequencing; improved; insight; network models; novel; predictive modeling; protein complex; protein function; protein protein interaction; public health relevance; research study; tool; yeast two hybrid system

DESCRIPTION (provided by applicant): The dramatic increase of genome sequences across multiple species is exponentially increasing the number of predicted proteins with unknown function. The traditional "one at a time approach" of characterizing factors will always be essential, but it helps to be able to have a global view of the functional connections between and among these proteins in order to aid in the generation of specific hypotheses. One important way to study protein function is to be able to ascertain which other proteins are associated with it. In this proposal, we aim to systematically generate a protein-protein interaction (PPI) data in the model organism, S. pombe. Next to budding yeast, the fission yeast S. pombe has the most easily manipulatable genome of any eukaryotic model organism, and yet it is evolutionarily distinct from S. cerevisiae. We aim to generate the fission yeast PPI map using a two-pronged platform: yeast two-hybrid methodology and co-affinity purification followed by mass spectrometry (AP/MS) approach. This work brings together two individuals (Yu and Krogan) who worked together to generate the most comprehensive co-complex PPI map to date in any organism (S. cerevisiae) using the AP/MS strategy (Krogan et al., Nature, 2006). Furthermore, more recently, Yu generated the most comprehensive two-hybrid dataset to date, also in budding yeast (Yu et al., Science, 2008). Therefore, we argue that, between the two groups, we have the experimental and bioinformatic expertise to carry out a comprehensive analysis of the protein interactome in fission yeast. From a purely evolutionary standpoint, valuable information would be obtained by comparing the interactome networks from both organisms since these two yeasts diverged around 330-420 million years ago. Additionally, analysis of interaction networks in S. pombe will provide novel information that cannot be obtained from studies performed with S. cerevisiae. For example, in its large complex centromere structure, the restriction of spindle construction to mitotic entry, redundant and inefficient origins of replication, gene regulation by histone methylation and chromodomain heterochromatin proteins, gene and transposon regulation by the RNAi pathway, telomere binding proteins, and the presence of introns in most genes, S. pombe is more similar to metazoans than is S. cerevisiae. Therefore, this project will not only have a huge impact on the fission yeast field but also will fuel evolutionary studies and will allow for interrogation of biological systems that are present in higher organisms but not in budding yeast.

描述（由申请人提供）： 跨多种物种的基因组序列的急剧增加是指数级增加了具有未知功能的预测蛋白质数量。表征因素的传统“一种方法”将始终是必不可少的，但是它有助于能够对这些蛋白质之间和这些蛋白质之间的功能连接有帮助，以帮助产生特定的假设。研究蛋白质功能的一种重要方法是能够确定哪些其他蛋白质与之相关。在此提案中，我们旨在在模型生物体S. Pombe中系统地生成蛋白质 - 蛋白质相互作用（PPI）数据。在萌芽的酵母旁边，裂变酵母菌S. pombe具有任何真核模型生物中最容易易于操纵的基因组，但它在进化上与酿酒酵母不同。我们旨在使用两管齐的平台生成裂变酵母PPI图：酵母两杂交方法和共亲密纯化，然后进行质谱（AP/MS）方法。这项工作汇集了两个人（YU和Krogan）共同努力，以使用AP/MS策略（Krogan等人，Nature，2006年）共同在任何生物体（S. cerevisiae）中生成最全面的共同复合PPI地图。此外，最近，Yu也生成了迄今为止最全面的两种杂交数据集，也是在发芽的酵母中（Yu等，Science，2008）。因此，我们认为，在两组之间，我们拥有实验和生物信息学专业知识，可以对裂变酵母中的蛋白质相互作用进行全面分析。从纯粹的进化角度来看，可以通过比较这两种生物体的相互作用网络来获得有价值的信息，因为这两种酵母在330-4.2亿年前差异左右。此外，对S. pombe中的相互作用网络的分析将提供新的信息，这些信息无法从酿酒酵母进行的研究中获得。 For example, in its large complex centromere structure, the restriction of spindle construction to mitotic entry, redundant and inefficient origins of replication, gene regulation by histone methylation and chromodomain heterochromatin proteins, gene and transposon regulation by the RNAi pathway, telomere binding proteins, and the presence of introns in most genes, S. pombe is more similar to metazoans than is S.酿酒酵母。因此，该项目不仅会对裂变酵母菌领域产生巨大影响，而且还将促进进化研究，并允许对 存在于较高生物体但不存在于发芽的酵母中的生物系统。