Coordination Funds

协调基金

• 批准号: 470769886
• 负责人: Professorin Dr. Melanie Brinkmann
• 金额: --
• 依托单位: Institut für Genetik
• 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/470769886?language=en
• 关键词: Coordination; Funds

Gene expression is a fundamental process controlled by a complex network of regulatory factors. Nuclear replicating DNA viruses typically cause chronic infections and depend on these complex host networks for their own gene expression. Simultaneously, they need to manipulate regulatory networks to avoid clearance and create a favorable environment for chronic viral infection. Failure or success at controlling gene expression networks ultimately determines whether the initial infection becomes abortive, or proceeds to a productive or persistent phase. Viral reservoirs associated with chronic infections can take different forms. Through continuous cycles of replication and re-infection, a productive persistence can be established. In contrast, a so-called non-productive persistence is based on the establishment of certain cell populations in which no or only very low virus production takes place. Regardless of which specific form of viral persistence is employed, successful establishment of viral reservoirs requires sophisticated mechanisms to counteract antiviral host responses and viral gene expression programs tailored to the environment within a given target cell. In this context, the central focus of the DEEP-DV consortium is to study the dedicated strategies employed by newly infecting DNA viruses to disrupt, evade, or exploit nuclear gene expression networks to achieve the desired infection outcome. The central hypothesis is that such viral strategies may vary depending on the specific nuclear environment and state of the host cell. However, there will be commonalities and as-of-yet undefined shared principles that are important across diverse nuclear DNA virus species and even across families. This is especially true for antiviral host responses and nuclear repressor complexes that have to be evaded or exploited by newly incoming viral genomes. DEEP-DV will investigate the early events of nuclear DNA virus infection to define these principles. Importantly, while such mechanisms are usually interrogated in a single viral system, the projects in DEEP-DV investigate different DNA viruses of the herpes-, polyoma- and adenovirus families. Since these viruses are evolutionarily ancient, and have co-evolved with their host over millions of years, we expect that the joint endeavor proposed here is ideally suited to uncover above principles. DEEP-DV brings together scientists with strong virological expertise, firm command of state of the art experimental methodologies (e.g. genome, transcriptome and epigenome analytics, RNP proteomics, single cell technologies and advanced imaging methods), and profound experience with bioinformatic data analysis. This endeavor seeks to open up new possibilities to understand and, ultimately, control acute and chronic DNA virus infections.

基因表达是一个由复杂的调控因子网络控制的基本过程。核复制DNA病毒通常会引起慢性感染，并依赖于这些复杂的宿主网络来表达自己的基因。同时，它们需要操纵调控网络以避免清除，并为慢性病毒感染创造有利的环境。控制基因表达网络的失败或成功最终决定了最初的感染是流产，还是进入生产或持续阶段。与慢性感染相关的病毒库可以采取不同的形式。通过连续的复制和再感染循环，可以建立富有成效的持久性。相反，所谓的非生产性持久性是基于某些细胞群的建立，其中不产生或仅产生非常低的病毒。无论采用哪种特定形式的病毒持久性，成功建立病毒储库需要复杂的机制来抵消抗病毒宿主应答和针对给定靶细胞内的环境定制的病毒基因表达程序。在这种情况下，DEEP-DV联盟的中心重点是研究新感染的DNA病毒所采用的专用策略，以破坏，逃避或利用核基因表达网络来实现所需的感染结果。核心假设是，这种病毒策略可能会根据特定的核环境和宿主细胞的状态而变化。然而，在不同的核DNA病毒物种之间，甚至在不同的家族之间，都会有一些共同点和尚未定义的共同原则。这对于必须被新进入的病毒基因组逃避或利用的抗病毒宿主反应和核阻遏物复合物尤其如此。DEEP-DV将研究核DNA病毒感染的早期事件，以确定这些原则。重要的是，虽然这些机制通常在单一病毒系统中进行研究，但DEEP-DV项目研究了疱疹病毒、多瘤病毒和腺病毒家族的不同DNA病毒。由于这些病毒在进化上是古老的，并且已经与它们的宿主共同进化了数百万年，我们希望这里提出的联合奋进非常适合揭示上述原则。DEEP-DV汇集了具有强大病毒学专业知识的科学家，对最先进实验方法的坚定指挥（例如基因组，转录组和表观基因组分析，RNP蛋白质组学，单细胞技术和先进的成像方法），以及生物信息学数据分析的丰富经验。这一奋进旨在开辟新的可能性，以了解并最终控制急性和慢性DNA病毒感染。