Het gebruik van elektronentomografie voor de opheldering van de structuur en assemblage van het pokkenvirus vaccinia
03 / 2004 - 12 / 2006
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO)
Pox viruses, such as vaccinia, represent the pinnacle of viral evolution. Although vaccinia was successfully used to eradicate smallpox the events of September 11, 2001 have again raised concerns about the potential of this, once devastating disease. These important pathogens have evolved the most complex structures and a life cycle that is unique. The virus has a DNA genome of 190Kb that encodes for 255 proteins, of which 100 are in the virus. The Griffiths group at EMBL has focused in details on the cell biology of the vaccinia life cycle and on the assembly and structure of the virus. They have recently proposed a detailed model of the viral membrane/DNA assembly in cells as well as providing a cartoon representation of the complex interfolding of membrane domains to form the infectious viruses. The novel approach of electron tomography offers a powerful approach for elucidating the structure and describing the assembly process at high resolution. The tomography group headed by Koster in Utrecht is a unique facility in the Netherlands, and only one of three in Europe and ten, worldwide. Preliminary analyses with this approach by Griffiths/Koster/Geerts have revealed its potential to ultimately solve the structure/assembly process. This proposal describes a goal-oriented project to elucidate the structure and assembly mechanism of the virus.