A mathematical and biophysical analysis of salmonella macrophage interactions

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Salmonella enterica causes a wide range of diseases in many animals. Economic losses to the farming industry through Salmonella infection are potentially very high, but also important is the fact that a number of serovars that infect animals can also cause food poisoning and gastroenteritis in humans. Salmonella infect specialised immune cells (macrophages) where the bacteria reside within an intracellular compartment called the salmonella-containing vacuole. Within the macrophage the bacteria may be killed, may hide, may grow and can cause the cell to die. The interaction between macrophages and salmonellae is critically important to the progression of disease. Controlling the numbers of bacteria within the macrophage is an important step in enabling the host to stop the bacteria growing and to survive infection. Many mechanisms involved in the interaction between Salmonella and macrophages are unclear. In particular little is known about how the macrophage physically interacts with the cell. The macrophage detects the presence of bacteria through specialised proteins called Pattern Recognition Receptors (PRRs) which induce macrophage responses to help the host control a salmonella infection. In this project I will use mathematical models to predict how PRR activity effects the process by which Salmonella infect macrophages and then test these theoretical assumptions using biological experiments. I will use physical techniques to investigate whether PRRs influence how Salmonella associate with macrophages. In the final part of the project I will compare how PRR activity affects the global response of macrophages to infection. This project will increase our understanding of how Salmonella infect macrophages and may deliver new targets for developing drugs to treat the diseases caused by these pathogens.