Tools for Functional Analysis and Cell Biology

功能分析和细胞生物学工具

• 批准号: 8375308
• 负责人: Jay C. Dunlap
• 金额: $ 61.2万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8375308
• 关键词: Air; Ally; Animals; Antibiotics; Area; Aspergillus; Aspergillus nidulans; Basic Science; Binding Sites; Biological; Biological Models; Cells; Cellular biology; Characteristics; Chemicals; Chromatin Structure; Communities; Computer Simulation; DNA Methylation; Data; Deposition; Desiccation; Development; Engineering; Enzymes; Epitopes; Eukaryota; Eukaryotic Cell; Expressed Sequence Tags; Focus Groups; Fungi Model; Gene Expression Profile; Gene Proteins; Genes; Genome; Genomics; Goals; Growth; Growth and Development function; Histones; Informatics; Knock-out; Light; Maps; Measurement; Mediating; Modeling; Molds; Molecular; Molecular Biology; Neurospora; Neurospora crassa; Nucleosomes; Pharmacologic Substance; Plants; Proteins; Proteomics; RNA; Regulator Genes; Regulatory Pathway; Reproduction spores; Research; Research Personnel; Science; Site; Systems Biology; Techniques; Technology; Testing; Variant; Work; Yeasts; asexual; base; functional genomics; fungal genetics; fungus; gene replacement; histone modification; improved; killings; knockout gene; mutant; new technology; novel; pathogen; predictive modeling; programs; response; success; tool; tool development; transcription factor

The central goal of the three interdependent efforts in this Program Project builds upon successful functional genomics, annotation, and expression analyses of Neurospora crassa, a premier filamentous fungus model for over 250,000 species of non-yeast fungi. A primary goal, targeted through molecular, cell biological, genomic and computational approaches, will be to understand how N. crassa transitions from mycelial growth to complete asexual spore development. We will focus on two key triggers of asexual development: light and desiccation. In addition, we will leverage our prior successes to expand systematic knockouts to an additional prominent model system, Aspergillus nidulans. Neurospora is a salient model for basic research in eukaryotes, as is Aspergillus, and fungi allied to these species include most animal and plant pathogens as well as industrial strains yielding antibiotics, chemicals, enzymes, and Pharmaceuticals. Gene predictions among the 9846 genes encoded by the fully sequenced 43 Mb Neurospora genome are supported by over 250,000 ESTs derived from this P01. During the past 4 years, we revolutionized the tools and techniques for gene knockouts in filamentous fungi and exceeded our initial goal by over 40%. Project #1 will complete the Neurospora gene knockouts and extend the systematic disruption of genes to Aspergillus. We will develop strains, tools, and background information in support of Projects #2 and #3, and of the overarching goal of understanding regulatory pathways governing filamentous fungal development. Projects #2 and #3 will aim to describe and reconstruct the cascading regulatory programs that underlie N. crassa's developmental response to light and air, from the level of chromatin structure through the gene regulatory network. Project #3 will use ChlP-seq mapping of histone modifications, transcription factor binding sites, sites of DNA methylation and nucleosome occupancy with corresponding transcriptome measurements to generate a deep description of genome and epigenome dynamics. Project #2, in an informatic-intensive systems biology approach, will integrate these data and use computational modeling to develop predictive models of the interconnected light and asexual development gene regulatory networks. These models will be fleshed out tested through incorporation of new data arising from Project #3 and refined via perturbation analyses facilitated through the use of strains developed in Project #1 and characterized using the tools employed in Project #3. This effort will anchor, promote, and exploit genomic exploration within model systems that provide gateways to the Kingdom of the Fungi.

该计划项目中三个相互依存努力的核心目标是成功的 神经孢子虫的功能基因组学，注释和表达分析，这是一种主要的丝状丝状 25万种非酵母菌真菌的真菌模型。通过分子，细胞针对的主要目标 生物学，基因组和计算方法将是为了了解N. crassa如何从 菌丝体的生长以完成无性孢子的发展。我们将专注于两个关键的无性触发器 发展：光和干燥。此外，我们将利用先前的成功来扩展系统 敲除额外的突出模型系统曲霉尼古拉人。 Neurospora是一个显着模型 真核生物的基础研究，曲曲霉也是如此，与这些物种结盟的真菌包括大多数动物和 植物病原体以及产生抗生素，化学物质，酶和药物的工业菌株。 由完全测序的43 Mb神经孢子基因组编码的9846基因之间的基因预测是 由超过250,000个EST衍生自此P01的支持。在过去的四年中，我们彻底改变了工具 以及丝状真菌中基因敲除的技术，并超过了40％以上。项目 ＃1将完成Neurospora基因敲除，并将基因的系统破坏扩展到 曲霉。我们将开发应变，工具和背景信息，以支持2和3的项目，以及 理解管理丝状真菌开发的监管途径的总体目标。 项目＃2和＃3的目的是描述和重构N的级联监管计划。 Crassa从染色质结构通过基因的水平对光和空气的发展反应 监管网络。项目＃3将使用组蛋白修饰的CHLP-seq映射，转录因子 结合位点，DNA甲基化和核小体占用率的位点，具有相应的转录组 测量以产生对基因组和表观基因组动力学的深入描述。项目＃2， 信息密集型系统生物学方法将将这些数据集成并使用计算建模到 开发相互连接的光和无性开发基因调节网络的预测模型。 这些模型将通过合并项目＃3和 通过使用项目＃1和 使用项目＃3中使用的工具进行表征。 这项工作将在模型系统中锚定，促进和利用基因组探索，以提供 通往真菌王国的门户。