Deciphering nanoscale interactions at the virus-host interface

We are interested in deciphering the complex interactions between Poxviruses and their host cells using the prototypic poxvirus, vaccinia (VACV), as a model system. As we are looking to investigate both the pathogen and its host, for these studies we combine cellular, molecular, and virological techniques with state-of-the-art technologies. These include automated small compound and image-based cell- and virus-targeting siRNA screening, advanced proteomics, live cell- and electron- microscopy technologies. Using these varied approaches we look to unravel the complexity of poxviruses and uncover the mechanisms they use to subjugate host cell functions to facilitate productive replication. Not only will these studies provide a more detailed understanding of the lifecycle of poxviruses and the cell biology of poxvirus infection, they will also uncover novel functions of cellular factors. Additionally, this work has the potential to define general strategies used by viruses to subjugate their host cells and, by extension, the possibility to develop cell-targeting, broad-spectrum antiviral agents.

Viral diseases represent one of the world’s highest social-economic burdens. Increased global trade and travel, climate change resulting in shifting viral vectors, and emergence of new and often deadly viruses, necessitates development of new research, diagnostic, and therapeutic tools to combat coming pandemic and epidemic infections. For this, a thorough understanding of the basic lifecycle of viruses and the cellular factors and functions required for viral replication is needed. In turn, as obligatory, intracellular parasites, viruses exploit cellular processes such as signalling, membrane trafficking, molecular sorting, etc. Thus viruses provide a valuable tool to study multiple aspects of normal cell function.

Our group is interested in deciphering the complex interactions between Poxviruses and their host cells. For these studies we combine cellular, molecular, and virological techniques with state-of-the-art technologies such as automated small compound and image-based cell- and virus-targeting siRNA screening, advanced proteomics, live cell-, electron-, and superresolution microscopy technologies. Using this combined approach we look to uncovering novel mechanisms by which poxviruses subjugate host cell functions to facilitate productive replication.

Particular focus is placed on investigating how poxviruses manipulate host cell endocytic machinery to their advantage1-3, unraveling the complex protein nanoarchitecture of poxvirus particles and their intracellular disassembly and assembly4, and determining the mechanisms by which these viruses modulate the host response to infection prior to viral gene expression5.

Not only will these studies provide a more detailed understanding of the cell biology of poxvirus infection, we have to opportunity to uncover novel functions of cellular factors. Additionally, this work has the potential to uncover general strategies used by viruses to subjugate their host cells and by extension the possibility to develop cell-targeting, broad-spectrum antiviral agents.