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WPL: Sarah Butcher

 

Determination of specific neutralizing epitopes for generation of therapeutic moAbs and proteins to be used in diagnostic assays.

We will align picornaviral sequences to identify common epitopes/antigens which will be synthesized and used as antigen for antibody production for diagnostics or therapy. Main locations: TU

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Studying virus structure, in relation to (known) receptors and human monoclonal antibodies.

By determining the 3D structure of selected clinical-relevant virus isolates by 3-dimensional electron microscopy and image processing (3DEM), X-ray crystallography and EM to reveal the position of the epitope; the exact 3D position on the virus bound by the receptor. Once the epitope is known, interfering antibodies can be designed with neutralising capacities. In addition, entry studies at AMC/REGA using light and electron cryo-tomography on infected cells will be performed to unravel the exact mechanism of the viral life cycle. Main location: UH

—Setting up standardized models for virus-host interaction by the use of human organ cultures (3D cultures).

With 3D cultures of both human epithelial airway and human gut, primary infection with picornaviruses can be mimicked and studied providing valuable information on virus entry, primary target cells and the relevance of entry receptors. In addition, the developed antibodies can be tested in vitro for neutralising and inhibitory properties. Main location: AMC

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Standardizing protocols for viral cloning, and generate infectious clones for all types.

We will generate T7 promotor-tagged full-length PCR clones of selected picornaviral sequences which are capable of replicating. We will also use this technique to generate infectious virus variants. Main location: TU