Nuclear, Genomic and Molecular Regulation of Type I Interferon Transcription

描述（由申请人提供）：我们这个探索性研究计划的长期目标是确定染色体构象和亚核位置如何影响宿主对病毒的反应。在先天免疫应答病毒过程中，染色体纤维折叠和并置的大规模核过程的意义和作用仍然相对未知。然而，这些过程代表了调节先天免疫系统的潜在治疗的未探索的表观遗传靶点。为了了解人类细胞中参与抗病毒反应的这些核过程，我们将描述病毒感染期间二倍体成纤维细胞和淋巴细胞基因组中调节染色体构象和I型干扰素位点亚核位置的分子机制。更好地了解I型干扰素产生的调控机制对于开发治疗病毒感染和自身免疫等炎症性疾病的治疗策略至关重要。

DESCRIPTION (provided by applicant): Our long-term goal of this exploratory research proposal is to determine how chromosome conformation and subnuclear position affect the host response to viruses. Significance and role of large-scale nuclear processes of folding and juxtaposition of chromosomal fibers during innate immune response to viruses remain relatively unknown. However, these processes represent unexplored epigenetic targets for modulating the innate immune system for potential therapies. To understand these nuclear processes involved in anti-viral response in human cells, we will characterize the molecular mechanisms that modulate chromosomal conformation and subnuclear location of the type I interferon locus in the genome of diploid fibroblasts and lymphoblasts during viral infection. A better understanding of the regulatory mechanisms involved in the production of type I interferons is fundamental to the development of therapeutic strategies for treating viral infections and inflammatory diseases such as autoimmunity.