The herpesvirus toolkit to elucidate the molecular biology of tunneling nanotubes (TNTs) and TNT-like cell projections

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 cross the extracellular matrix and/or may reach and dock onto other, distantly located, cells, resulting in exchange of biological information between these previously unconnected cells. These cell projections have been termed a.o. tunneling nanotubes (TNTs), tumor microtubes (TMs) and invadopodia. However, it is currently not entirely clear if these different cell projections are separate types of structures or whether they to some extent functionally and/or structurally overlap, which cellular proteins are involved in their formation, stabilization and attachment to other cells, and which type of molecular information they can spread. We have discovered that herpesviruses, via the viral US3 protein kinase, trigger the formation of cell projections that show functional and structural characteristics of TNTs, TMs and invadopodia. In addition, via a phospho-proteome screen, we have identified candidate cellular proteins involved in these cell projections. Based on exciting recent data by the candidate, the purpose of this FWO PhD fellowship application is to use this herpesvirus toolkit to generate novel insights in the molecular biology of this fascinating type of long-distance intercellular communication.