Molecular Virology and Systems Biology Screening Core

该计划项目旨在系统地解决有关HIV-1感染的先天反应之间相互作用的关键问题。我们预计将剖析细胞传感器和效应器的完整库，这些传感器和效应器涉及对HIV-1做出反应的固有信号通路。此外，这些途径之间的限速成分和串扰将提供有关应对艾滋病毒-1的重要关键角色的关键信息。我们还期望对这些途径调控的HIV-1感染的动力学以及这些途径对感染的临床结果的影响有一个新的理解。对这些过程的系统水平的理解将被用来构建数学模型，可以预测这些感染艾滋病毒-1的途径的行为。这些关于宿主-病原体界面的综合信息对于未来抗病毒和疫苗方法的优化将是无价的。由于该方法的基因组学性质，在计划项目范围内进行的科学项目将在很大程度上依赖于病毒和高通量形式的siRNA、shRNA和cDNA技术的大规模生产。分子病毒学和系统生物学筛选核心的目标是通过提供最先进的细胞基因组学技术和分子病毒学工具，在大规模和系统生物学筛选方法的各个方面为科学家提供支持。该协会在系统生物学领域拥有丰富的经验。科尼格博士将提供她11年来在病毒学方面的集体专业知识，以及她在开发和使用系统生物学筛查工具方面的经验。这些研究有望为调节对艾滋病毒感染的早期免疫反应的细胞和病毒过程提供全球分子洞察。

This program project seeks to systematically address crucial questions about the interplay between innate responses to HIV-1 infection. We anticipate to dissect the complete repertoire of cellular sensors and effectors involved in the innate signaling pathways that respond to HIV-1. Moreover, the rate-limiting components and the crosstalk between these pathways will provide critical information about important key players in the response to HIV-1. We also anticipate to acquire a novel understanding of the kinetics of HIV-1 infection regulated by these pathways and the effect of these pathways on the clinical outcome of infection. The systems-level understanding of these processes will be used to construct mathematical models that can predict the behavior of these pathways to HIV-1 infection. These integrated pieces of information about the host-pathogen interface will be invaluable for future optimization of antiviral and vaccine approaches. Scientific projects taking place within the scope of the Program Project will rely to a great extent on largescale production of viruses and siRNA, shRNA and cDNA technologies in high-throughput format as a result of the genomics nature of the approach. The goal of the Molecular Virology and Systems Biology Screening Core is to support the scientists in all aspects ofthe large-scale and system-biology screening approaches by providing state-of-the-art cellular genomics technologies and molecular virology tools. The PI has significant experience in the field of systems-biology. Dr. KOnig will provide her collective expertise in Virology for over 11 years and her experience in developing and employing systems-biology screening tools. These studies are expected to provide global molecular insight into cellular and viral processes that regulate early immune responses to HIV infection.