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

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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.