Production of a molecular network pathway for herpesviruses and the nucleolus.

哺乳动物的细胞核是一种膜结合的细胞器。在细胞核内存在几个核体或亚核结构。其中最大的是核仁。多年来，核仁的作用被认为是核糖体生物发生的场所。然而，最近的分析表明，核仁可能在细胞生物学的许多方面发挥重要作用。理解这些新的非经典作用的核仁的一种新方法是分析病毒和核仁之间的关系。许多重要的病毒编码蛋白定位于核仁，这种定位被认为是这些病毒蛋白正确发挥功能和病毒有效复制所必需的。因此，如果我们能够理解为什么病毒蛋白质靶向核仁，以及核仁如何帮助这些病毒蛋白质发挥功能，这可能有助于理解核仁的更广泛的非经典作用。因此，本研究的目的是分析疱疹病毒感染期间核仁内的变化。为了做到这一点，我将确定在感染过程中细胞蛋白质是如何丢失或移动到核仁中的。此外，我们将确定哪些病毒蛋白质负责这些变化。一旦确定，我们将评估当我们抑制核仁蛋白丢失或移动到核仁时，疱疹病毒的复制会发生什么。最后，一旦确定了疱疹病毒蛋白和核仁之间的相互作用，我将交叉引用这些数据与现有的数据库，这些数据库已经映射了疱疹病毒蛋白之间的蛋白质-蛋白质相互作用，也映射了细胞蛋白之间的蛋白质-蛋白质相互作用。然后将这些数据组装起来，建立一个分子相互作用网络，显示每种病毒蛋白质破坏或利用宿主细胞中的哪些分子途径。这可以追溯到核仁蛋白，这将有助于理解核仁蛋白的功能。

The mammalian cell nucleus is a membrane bound organelle. Within the nucleus several nuclear bodies or subnuclear structures exist. The largest of these is the nucleolus. For many years the role of the nucleolus was thought to be the site of ribosome biogenesis. However, recent analysis suggests that the nucleolus may have important roles in many aspects of cell biology. A novel way to understand these novel non-classical roles of the nucleolus is to analyse the relationship between viruses and the nucleolus. Many important virally encoded proteins localise to the nucleolus and this localisation is thought to be essential for the correct functioning of these viral proteins and efficient replication of the virus. Therefore, if we can understand why the viral proteins target the nucleolus, and how the nucleolus helps these viral proteins function it may help in understanding the wider non-classical roles of the nucleolus in general. Therefore the aim of this fellowship is to analyse the changes within the nucleolus during a herpesvirus infection. To do this I will determine the way cellular proteins are either lost or moved into the nucleolus during an infection. Moreover, we will identify which viral proteins are responsible for these changes. Once identified, we will then assess what happens to the replication of the herpesvirus when we inhibit the nucleolar proteins from being either lost or moved into the nucleolus. Finally, once the interaction between the herpesvirus proteins and the nucleolus have been identified, I will cross reference this data with existing databases which have mapped protein-protein interactions between herpesvirus proteins and also databases which have mapped protein-protein interactions between cellular proteins. This data will then be assembled to build up a molecular interaction network, showing which molecular pathways in the host cell each viral protein subverts or utilises. This can then be traced back to the nucleolar proteins which will help in understanding of how the nucleolar proteins function.