Research objectives and content
The Yersinia Yops are a set of virulence and virulence-accessory factors produced by the three species of Yersinia that are pathogenic for humans. These Yops are injected into the cytosol of eukaryotic cells by extracellular bacteria adhering at the cell surface. Several Yops with essential roles in Yersinia pathogenesis are homologous to eukaryotic proteins involved in signal transduction. The Yersinia species may express these Yops during infection of the reticulo-endothelial system to act synergistically to interfere with several critical host functions. The biological outcome of this process is the ability of the Yersiniae to suppress the development of a cellular immune response. One of the Yops indispensable for virulence is YpkA. YpkA shows extensive homology with the family of eukaryotic serine/threonine protein kinases. YpkA is auto-phosphorylated, but target cell substrates have to be identified. The objectives of the proposed project are: 1) to elucidate the cellular function and 2) to identify the molecular target of YpkA. Central to these objectives is the introduction of YpkA into the target cells, which will be accomplished by heterologous expression from an inducible eukaryotic expression vector and by the use of a mutant Yersinia, overexpressing YpkA. Then, using a variety of biochemical and cell biological techniques. the cellular target will be characterized and functional aspects of YpkA will be studied at a molecular level.
Training content (objective, benefit and expected impact)
The proposed study will allow thorough scientific training at the interface of cell biology and microbiology. The objectives will be expansion of already obtained knowledge in bacterial pathogenesis, in combination with acquiring fresh knowledge on cell biology aspects of bacterial-host cell interactions. Training at the host institute will result in a network of international co-operation. and provide a solid base for continuing and expanding similar studies in the home country upon return.