CHARACTERIZAION OF HUMAN LANGERHANS CELLS GROWN FROM MOB

进入宿主细胞的细胞核是免疫的先决条件。 许多病毒的复制。 单纯疱疹病毒1型（HSV-1）由 病毒衣壳太大而不能进入细胞核。 因此，HSV-1的双链DNA基因组被引入到 宿主细胞的核在一个严格调控的脱壳步骤。 的 病毒与宿主的相互作用控制着疱疹生命中的这一关键步骤 周期在很大程度上仍然未知。 这项研究的目的是确定疱疹病毒衣壳 停靠在细胞的核孔上，脱去外壳，并将其DNA输送到 原子核 由于病毒经常利用正常的细胞过程， 我们对一般核进口的理解的进展将被用来 研究疱疹基因组核进入的具体问题。 三 提出了细胞生物学、生物化学和遗传学的方法 用于定义介导这一过程的病毒和细胞因子。 研究这些重要的病毒-宿主相互作用将使我们更接近 来理解病毒学中一个长期存在的谜团：为什么 衣壳很容易脱外套，而新组装的外向衣壳不？ 此外，这项工作将进一步促进我们对核武器的普遍了解， 运输 最后，所提出的实验的结果可能导致 开发更有效的抗病毒疗法， 高效的基因传递系统。 这个计划将在耶鲁大学阿里·海列纽斯的实验室里进行 大学医学院，将大大提高我的经验 作为一名医生/科学家，因为它提供病毒学和 细胞生物学 此外，研究职业奖将提供 为了实现我的长期目标，我接受了必要的培训： 学术医学，主要强调独立研究 这一计划将从与海伦纽斯博士的合作中产生。

Access to the nucleus of the host cell is a prerequisite for the replication of many viruses. Herpes simplex virus-1 (HSV-1) consists of a viral capsid that is too large to enter the nucleus itself. Therefore, HSV-1's double-stranded DNA genome is introduced into the nucleus of the host cell in a tightly regulated uncoating step. The viral-host interactions that control this key step in the herpes life cycle remain largely unknown. The goal of the proposed research is to determine how the herpes capsid docks at the cell's nuclear pore, uncoats, and delivers its DNA into the nucleus. Since viruses often exploit normal cellular processes, recent advances in our understanding of general nuclear import will be used to study the specific problem of herpes genome nuclear entry. Three approaches - cell biological, biochemical, and genetic - are proposed for defining the viral and cellular factors that mediate this process. Studying these important viral-host interactions will bring us closer to understanding a long-standing mystery in virology: why do incoming capsids readily uncoat, while newly-assembled outgoing capsids do not? In addition, this work will further our general understanding of nuclear transport. Finally, results of the proposed experiments may lead to the development of more effective antiviral therapies as well as more efficient gene delivery systems. The proposed project, to be conducted in Ari Helenius's lab at Yale University School of Medicine, will significantly enhance my experience as a physician/scientist, since it offers training in both virology and cell biology. Furthermore, the Research Career Award will provide the necessary training for me to reach my long-term goal: a career in academic medicine, with primary emphasis on an independent research program that will arise from this work with Dr. Helenius.