Integrative functional genomics of DNA virus infections

DNA病毒感染的综合功能基因组学

• 批准号: 470667745
• 负责人: Professorin Dr. Caroline Friedel
• 金额: --
• 依托单位: Lehr- und Forschungseinheit Bioinformatik
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/470667745?language=en
• 关键词: Integrative; functional; genomics; DNA; virus

A central aim of DEEP-DV is the identification of common mechanisms and differences in host and viral gene regulation between DNA virus infections. For this purpose, we will leverage functional genomics sequencing data generated by the individual DEEP-DV projects to address their specific project objectives. These data provide a rich resource for Z01 for comparative analyses that go beyond the individual project aims and integrate across DEEP-DV projects and different functional genomics assays. To facilitate data integration, we will develop standardized analysis workflows, a data and analysis sharing platform (the DEEP-DV Hub) as well as approaches for mining public data. This will allow us to perform an extensive analysis of transcriptional and epigenetic regulation across different DNA viruses using both DEEP-DV-internal and public data. We will develop methods to investigate and compare transcriptional and epigenetic changes and their interplay during infection with different DNA viruses as well as epigenetic priming prior to infection for rapid transcriptional responses. In addition, we will focus on promoter proximal RNA Polymerase II (RNAPII) pausing, premature transcription termination and their interplay in HSV-1 and other DNA virus infections. These research questions arise from preliminary observations on a widespread RNAPII pausing loss in HSV-1 infection and premature transcription termination at polyadenylation sites. The latter has previously been associated with inhibition of the CDK9 kinase. Notably, CDK9 is required for the release of paused RNAPII from the promoter and its inhibition arrests RNAPII in a paused state. Thus, Z01 will resolve the heterogeneous roles of CDK9 during HSV-1 infection as well as the role of the HSV-1 immediate-early protein ICP22, which is known to interact with CDK9. All results will be incorporated into the DEEP-DV Hub, which will provide the foundation for a public knowledgebase on DNA virus infections pursued in a putative second funding period.

DEEP-DV的中心目标是鉴定DNA病毒感染之间宿主和病毒基因调控的共同机制和差异。为此，我们将利用个别DEEP-DV项目产生的功能基因组测序数据来解决其特定的项目目标。这些数据为Z 01提供了丰富的资源，用于超越单个项目目标的比较分析，并整合了DEEP-DV项目和不同的功能基因组学检测。为促进数据整合，我们将开发标准化的分析工作流程、数据和分析共享平台（DEEP-DV Hub）以及挖掘公共数据的方法。这将使我们能够使用DEEP-DV内部和公共数据对不同DNA病毒的转录和表观遗传调控进行广泛的分析。我们将开发方法来调查和比较转录和表观遗传的变化和它们之间的相互作用，在感染不同的DNA病毒，以及表观遗传引发感染前的快速转录反应。此外，我们将集中在启动子近端RNA聚合酶II（RNAPII）暂停，过早的转录终止和它们在HSV-1和其他DNA病毒感染的相互作用。这些研究问题来自于对HSV-1感染中广泛的RNAPII暂停损失和多聚腺苷酸化位点处的过早转录终止的初步观察。后者以前与CDK 9激酶的抑制有关。值得注意的是，CDK 9是从启动子释放暂停的RNAPII所必需的，并且其抑制将RNAPII停滞在暂停状态。因此，Z 01将解决CDK 9在HSV-1感染期间的异质性作用以及HSV-1立即早期蛋白ICP 22的作用，已知ICP 22与CDK 9相互作用。所有结果都将纳入DEEP-DV中心，该中心将为在假定的第二个供资期内开展的DNA病毒感染公共知识库提供基础。