Functional Genomics of Dictyostelium

盘基网柄菌的功能基因组学

• 批准号: 8658304
• 负责人: ADAM KUSPA
• 金额: $ 86.2万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-19 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8658304
• 关键词: Amoeba genus; Architecture; Bacteria; Biological Models; Communities; Computational Technique; Computer Simulation; Computer software; Computing Methodologies; Consensus; Data; Data Set; Development; Dictyostelium; Disease; Eukaryota; Eukaryotic Cell; Genes; Genetic; Growth; Human; Imagery; Immune response; Infection; Methods; Modems; Natural Immunity; Pathway interactions; Phenotype; Physiological; RNA Sequences; Research; Research Personnel; Resources; System; Techniques; Testing; Transcriptional Regulation; Work; base; chromatin immunoprecipitation; computer science; data mining; functional genomics; gene function; improved; mutant; network models; programs; research study; response; scaffold; tool development; transcription factor

DESCRIPTION (provided by applicant): This Program Project is aimed at understanding the mechanisms that control growth and multicellular development in Dictyostelium. In the previous project period we took a functional genomics approach to high-throughput mutant phenotyping, transcriptional profiling, and computational modeling that allowed us to draw functional inferences for hundreds of genes. Over the next five years we will focus our efforts on understanding transcriptional control during development and bacterial recognition, both during the growth of solitary Dictyostelium amoebae and in the context of an innate immune response during their development. We will intersect transcriptional profiling data with physiological data to extract information about the genetic networks that coordinate bacterial recognition in Dictyostelium and characterize the genes and pathways involved. We will also test which regulators are responsible for the dramatic transcriptional changes that accompany Dictyostelium development. We will use RNA sequencing (RNA-seq) and Chromatin Immunoprecipitation (ChlP-seq) to identify genes that are directly regulated by these transcription factors. We will develop computational techniques and integrative data mining to infer gene function and to construct consensus gene network models for use as scaffolds upon which we can propose additional experiments and add layers of information from other experiments. We also propose to implement the new methods within modem server-based software architecture with visualization-rich interactive interfaces that will make the entire planned data analytics transparent and operable by biologists with no computer science background. This work will help establish the amoeba as a model system for the study of innate immunity, leading to the development of tools and techniques that can be applied to understanding the response of eukaryotic cells to bacteria. Our strains, data, and software will be freely available to the research community and well integrated with dictyBase, the primary Dictyostelium community resource and data warehouse.

描述（由申请人提供）：该计划项目旨在了解控制Dictyostelium的生长和多细胞发展的机制。在上一个项目期间，我们采用了一种功能性基因组学方法来进行高通量突变体表型，转录分析和计算建模，使我们能够为数百个基因提出功能推断。在接下来的五年中，我们将集中精力在开发和细菌识别过程中的转录控制上，无论是在单独的dictyostelium opoebae的增长过程中，还是在开发过程中先天免疫反应的背景下。我们将将转录分析数据与生理数据相交，以提取有关遗传网络的信息，这些遗传网络在Dictyostelium中协调细菌识别并表征所涉及的基因和途径。我们还将测试哪些监管机构负责Dictyostelium Development伴随的巨大转录变化。我们将使用RNA测序（RNA-SEQ）和染色质免疫沉淀（CHLP-SEQ）来识别由这些转录因子直接调节的基因。我们将开发计算技术和集成数据挖掘，以推断基因功能，并构建共识基因网络模型作为脚手架，我们可以在上面提出其他实验并添加其他实验中的信息层。我们还建议在基于调制解调器服务器的软件体系结构中实现新方法，并具有可视化丰富的交互式接口，这将使无计算机科学背景的生物学家可以使整个计划的数据分析透明且可操作。这项工作将有助于将变形虫建立为研究先天免疫的模型系统，从而开发工具和技术，可用于理解真核细胞对细菌的反应。我们的应变，数据和软件将免费提供给研究社区，并与dictybase良好地集成，即dictyostelium社区资源和数据仓库。