Investigating the interaction between Photorhabdus Virulence Cassette nanosyringes with immune cells.

The use of biologically active proteins for biomedical applications is becoming increasingly important as they can exhibit highly specific and potent activities. Good examples include antibody and cytokine-based approaches. It should be noted however that the majority of current successful polypeptide-based tools such as these act externally to host cells or require endocytic processing. A major frustration remains in getting active polypeptides across biological membranes and targeting them into specific compartments within target cells. There is an unmet need to develop more sophisticated tools for intracellular biomedical applications. Nature has evolved highly diverse and efficient molecular mechanisms for the translocation of biologically active polypeptides across biological membranes. Secreted bacterial toxins represent self-contained and highly adapted molecular devices for the delivery of active polypeptides into host cells. Advanced synthetic biology techniques now afford the opportunity to re-engineer toxin systems in order to adapt them for alternative desirable functions. The insect pathogenic bacterium Photorhabdus deploys astonishing nanoscale protein syringes to deliver payload toxins into host cells. In this project we will build upon significant previous progress in re-engineering these devices into viable intracellular protein drug delivery tools. These tools will ultimately be valuable as both research tools in life sciences and have the potential to address a huge range of human or animal diseases such as cancer, immunology disorders and enzyme deficiencies.