Project

Uncovering the mechanism underlying and consequences of alphaherpesvirus-induced formation of tunneling nanotubes (TNTs)

Code
01D21923
Duration
01 October 2023 → 30 September 2027
Funding
Regional and community funding: Special Research Fund
Research disciplines
  • Natural sciences
    • Virology
    • Cellular interactions and extracellular matrix
    • Cytoskeleton
  • Medical and health sciences
    • Adaptive immunology
    • Innate immunity
Keywords
tunneling nanotubes alphaherpesviruses intercellular communication
 
Project description

Communication between cells is of essential importance in all physiological and pathological processes in multicellular organisms. A relatively recently discovered method of cell-cell communication consists of the formation of long cell projections by one cell that may reach to and dock onto other, distantly located, cells, resulting in exchange of biological information between these previously unconnected cells. These cell projections have been termed tunneling nanotubes (TNTs). The research team of the candidate has discovered that, upon infection of cells with the alphaherpesvirus pseudorabies virus, the viral US3 protein kinase triggers the formation of TNTs. However, the mechanism underlying US3-induced TNT formation is incompletely understood. Based on preliminary data and a US3 phosphoproteome screen, key insights in this mechanism will be generated in the current PhD research. In addition, it is currently unclear which type of biomolecules can be transported from one cell to another via US3-induced TNTs and whether such communication may alert the immune response. The current PhD research aims to clarify this via state-of-the-art technology (including photoporation) and immunological readouts. Finally, there are indications that formation of TNTs may have therapeutic potential in the field of alphaherpesvirus-based oncolytic virotherapy. The PhD candidate will assess whether different alphaherpesvirus US3 homologs may have different potential in this respect. Overall, the current PhD research will generate new insights in the mechanism underlying alphaherpesvirus-induced TNTs (and possibly TNTs in general) and the type of (immunologically relevant) information that is spread via this fascinating but still incompletely understood method of intercellular communication.