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A novel approach to elucidate vaccinia virus three-dimensional structure: characterization by electron tomography

A novel approach to elucidate vaccinia virus three-dimensional structure: characterization by electron tomography

Objective

The project aims at getting a much better understanding of vaccinia virus (VV) by obtaining for the first time 3-dimensional (3D) images of the virus in different stages. Vaccinia, which was successfully used as a vaccine to eradicate smallpox, is an attractive candidate for cancer therapy and vaccination programs using DNA-recombinant technology.

VV belongs to the poxvirus family, the most evolved group of viruses, and has developed a very complex structure and life cycle. Many aspects of vaccinia remain poorly understood, when not openly controversial. Electron microscopy characterization is obscured by the limitations of the conventional 2D techniques. The novel approach of electron tomography offers a powerful tool to elucidate the 3D structure of the virus. Specifically, electron tomography will be applied to the predominant infectious form of the virus (the intracellular mature virus), the isolated internal core undergoing transcription, and to thick sections preparations of infected cells.

With the resulting models and their combination, we will be able to provide a detailed 3D description of these viral forms and the transformation process of the virus. The home laboratory will be the group headed by Dr. Koster at Utrecht University. However, the project will be carried out in close collaboration with Dr. Gareth Griffiths and Dr. Krijnse-Locker's group, at the EMBL in Heidelberg. The EMBL group has more than ten years work experience on VV, whereas Dr. Koster's group is one of the leading groups in electron tomography.

Actually, only two other laboratories in Europe and about ten worldwide can equal the facility in Utrecht. From a personal point of view, learning from both different expertises will allow me to considerably widen my training as an electron microscopist and structural biologist. In summary, this project offers to me an excellent opportunity to learn an emerging methodology, expand my skills and enrich my scientific perspective.

Coordinator

UNIVERSITEIT UTRECHT

Address

Netherlands

Administrative Contact

Arie J. VERKLEIJ (Professor)

Project information

Grant agreement ID: 501540

  • Start date

    1 April 2005

  • End date

    31 March 2007

Funded under:

FP6-MOBILITY

  • Overall budget:

    € 149 276

  • EU contribution

    € 149 276

Coordinated by:

UNIVERSITEIT UTRECHT

Netherlands