Grant: Operating Grant

Salmonella bacteria reside in the intestinal tracts of livestock or wild animals and can be transmitted to humans via contaminated food or water to cause typhoid fever and diarrhoea, which pose major health problems throughout the world. White blood cells can normally destroy invading microorganisms by engulfing them and then delivering destructive enzymes that kill the bacteria. This part of our innate immune system is one of the primary lines of defence against invading pathogens but Salmonella species have evolved mechanisms to avoid this destruction; the bacteria is able to get into other cell types on its own, such as the cells lining our intestines, where it can halt the delivery of the destructive enzymes, allowing the bacteria to live and multiply within the cell. Ultimately the bacteria can either cause food poisoning-like symptoms from inside these cells or it can escape the confines of the cell and spread throughout the body to cause typhoid fever. The work proposed here focuses on trying to understand, from a broad view, how Salmonella is able to so efficiently control its host cells. Previous work from many other laboratories has made significant progress in understanding some aspects of this process but we aim to apply some cutting edge technology that we have had a role in developing in order to take a step backwards and ask 'What is going on in the cell as a whole?' As our group has led some of the technology development and also has significant background in the biological aspects of this problem, we have a unique ability to contribute to the overall picture of how this important pathogen affects us. The anticipated benefit of this work will be a much better understanding of how pathogens such as Salmonella are able to bypass our immune system. Such knowledge will allow us to make a more rational approach to drug design and therapies since we will be able to target specific processes unique to Salmonella.