Functional Analysis and Systems Biology of Filamentous Fungi

丝状真菌的功能分析和系统生物学

• 批准号: 7799814
• 负责人: Jay C. Dunlap
• 金额: $ 197.15万
• 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 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7799814
• 关键词: Functional; Analysis; Systems; Biology; Filamentous

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：该计划项目中三个相互依存的努力的核心目标建立在成功的功能基因组学，注释和表达分析的Neurospora Crassa，这是250,000种非野生east真菌的主要丝状真菌模型。通过分子生物学，基因组和计算方法针对的主要目标将是了解从菌丝体生长到完整无性孢子发育的Crassa梭菌过渡。我们将重点关注无性发展的两个关键触发器：光和干燥。此外，我们将利用先前的成功来将系统的淘汰赛扩展到其他突出的模型系统Aspergillus Nidulans。 Neurospora和曲绿菌一样是真核生物基础研究的显着模型，与这些物种结合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 Neurospora基因组编码的9846个基因中的基因预测得到了来自该P01的250,000多个EST。在过去的四年中，我们彻底改变了丝状真菌中基因敲除的工具和技术，并将我们的最初目标超过40％。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。我们将开发菌株，工具和背景信息，以支持2和3的项目，以及了解有关丝状真菌开发的监管途径的总体目标。项目＃2和＃3将旨在描述和重建N. Crassa对光线和空气的发展响应的级联监管计划，从染色质结构通过基因调节网络的水平。项目＃3将使用组蛋白修饰，转录因子结合位点，DNA甲基化位点和核小体占用位置的CHLP-seq映射，并具有相应的转录组测量值，以产生对基因组和表观基因组动力学的深入描述。项目＃2在信息密集型系统生物学方法中，将整合这些数据并使用计算建模来开发相互联系的光和无性开发基因调节网络的预测模型。这些模型将通过纳入项目＃3引起的新数据来进行充实，并通过扰动分析通过在项目＃1中开发的菌株进行促进并使用项目＃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，这些探索是通往真菌王国的门户。