Functional Analysis and Systems Biology of Filamentous Fungi

丝状真菌的功能分析和系统生物学

基本信息

批准号：
7814793
负责人：
Jay C. Dunlap
金额：
$ 134.54万
依托单位：
DARTMOUTH COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7814793
关键词：
Administrative Supplement Air Ally Animals Antibiotics Aspergillus Aspergillus nidulans Basic Science Binding Sites Biological Biological Models Biology Cells Chemicals Chromatin Chromatin Structure Classification Communities Complex Desiccation Development Electronic Mail Employment Enzymes Epigenetic Process Equipment and Supplies Eukaryota Exposure to Faculty Fluorescence Microscopy Funding Fungi Model Gene Expression Profile Gene Proteins Genes Genome Genomics Goals Grant Growth Growth and Development function Guidelines Knock-in Mouse Knock-out Light Location Maps Measurement Modeling Molds National Institute of General Medical Sciences Neurospora Neurospora crassa Occupations Ohio Oligonucleotides Parents Pharmacologic Substance Plants Postdoctoral Fellow Program Research Project Grants Proteomics Public Health Recovery Regulator Genes Regulatory Pathway Reproduction spores Research Research Infrastructure Research Personnel Seasons Series Students Systems Biology Techniques Technology Unemployment United States National Institutes of Health Universities Work Writing Yeasts asexual base fundamental research fungal genetics fungus genome-wide graduate student histone modification killings knockout gene parent grant pathogen programs protein protein interaction response success tool transcription factor

项目摘要

DESCRIPTION (provided by applicant): This proposal for supplementary funding, submitted under ARRA guidelines NOT-OD-09-058 (NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications) extends the scope of the parent Program Project grant. The overall effort centers on Neurospora crassa, a premier filamentous fungus model for over 250,000 species of non-yeast fungi. A primary goal is to understand how N. crassa transitions from mycelial growth to complete asexual spore development. We 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 and Aspergillus are salient models for basic research in eukaryotes; fungi allied to these species include most animal and plant pathogens as well as industrial strains yielding chemicals, enzymes, and pharmaceuticals. Over the first 5 years of prior support we revolutionized the technology for gene knockouts in filamentous fungi, exceeding our initial target by >50%. Project #1 completes Neurospora gene knockouts and extends systematic disruptions to Aspergillus. In support of the overarching goal of understanding regulatory pathways governing filamentous fungal development, in Projects #2 and #3, knockout and knock-ins are created via high throughput techniques. The Project #1 Supplement creates a new Aspergillus aim focused on proteomic analyses to describe the composition and location of intracellular complexes, while completing knockout cassettes for 1242 genes added to the Aspergillus genome since the parent grant was submitted. In the parent grant Projects #2 and #3 will describe and reconstruct the regulatory cascade that underlies N. crassa's developmental response to light and air, from the level of chromatin structure through the gene regulatory network, via ChlP-seq mapping of histone modifications, transcription factor binding sites, and epigenetic marks, correlating these with transcriptome measurements to generate a deep description of genome and epigenome dynamics. The Supplement to Project #3 expands the scope of this considerably by incorporating two new investigators and an alternative approach that has identified additional regulators. In terms of the ARRA, the supplements expand the scope of the original aims by adding projects that will vastly accelerate the pace ofthe work and that can be completed within 2 years. They allow for job creation and retention by adding a junior faculty New Investigator not yet supported by the NIH, employing an unemployed technician, three unemployed postdocs, two graduate students, restoring to full employment another postdoc, and making substantial purchases of US-made supplies and equipment. PUBLIC HEALTH REVELANCE: Filamentous fungi, typically known as molds, are common animal and plant pathogens, but they are also widely used as industrial strains to provide antibiotics, chemicals, enzymes, and pharmaceuticals. We'd be dead without them but they can kill us. We seek to understand how genes and proteins work together to regulate fungal growth and development, so as to enhance the good things and control the bad things produced by fungi. This supplement would support an NIH New Investigator, and employ or restore to full employment a technician, four postdocs, and two students.

描述（由申请人提供）：根据ARRA指南提交的补充资金提案，NOT-OD-09-058（NIH宣布可用于竞争性修订申请的恢复法案资金）扩展了父母计划项目赠款的范围。总体努力集中在Neurospora Crassa上，这是一种主要的丝状真菌模型，用于25万种非酵母菌真菌。一个主要目标是了解乳杆菌如何从菌丝体增长到完成无性孢子的发展。我们专注于无性开发，光线和干燥的两个关键触发因素。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。神经孢子和曲曲霉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化学物质，酶和药物的工业菌株。在事先支持的头5年中，我们彻底改变了丝状基因敲除技术真菌，超过我们的初始目标> 50％。项目＃1完成了Neurospora基因敲除，并将系统的破坏扩展到曲霉。为了支持理解有关丝状真菌开发的监管途径的总体目标，在项目＃2和＃3中，淘汰和敲门是通过高吞吐量创建的。项目＃1补充剂创建了一个新的曲霉瞄准剂，重点是蛋白质组学分析，以描述细胞内复合物的组成和位置，同时为添加到曲绿木基因组中的1242个基因完成基因敲除盒，因为父母赠款已提交。在父母赠款项目中，＃2和＃3将描述和重建n。crassa对光和空气的发育响应的基础的调节级联，从染色质结构通过基因调节网络，通过组蛋白修饰的CHLP-seq映射（转录因子结合位点和表观遗传标记将它们与转录组测量相关联，以产生对基因组和表观基因组动力学的深刻描述。项目＃3的补充通过纳入了两个新的研究者和一种确定其他监管机构的替代方法，从而大大扩展了这一范围。就ARRA而言，补充剂通过添加将大大加快工作节奏的项目来扩大原始目标的范围，并且可以在2年内完成。他们允许创造就业机会并通过添加一名初级教职员工来保留新调查员，尚未得到NIH的支持失业的技术员，三个失业的博士后，两名研究生，恢复全部就业后，并大量购买了美国制造的用品和设备。公共卫生启示：丝状真菌（通常称为霉菌）是常见的动物和植物病原体，但它们也被广泛用作工业菌株，可提供抗生素，化学物质，酶和药物。没有他们，我们会死，但他们可以杀死我们。我们试图了解基因和蛋白质如何共同调节真菌的生长和发育，以增强好东西并控制真菌产生的坏事。该补充剂将支持NIH的新调查员，并雇用或恢复全部就业的技术人员，四名PostDocs和两名学生。