Both environmental and genetic factors influence susceptibility to tuberculosis; this project will identify and investigate polymorphisms in genes that may increase susceptibility to tuberculosis.
This project aims to develop our understanding of the genetic control of TB. We will identify new genes involved in resistance to TB by screening genetically modified mice for susceptibility to aerosol TB infection. We already have three strains of mice with identified genetic mutations, identified by additional screens, and one arm of the PhD project will involve characterizing the involvement of these genes in immunity to tuberculosis. This will involve testing how these genes influence the containment of bacterial growth, the development of protective immunity to infection and the inflammatory response generated following infection. Second, we shall then examine the equivalent human genes, to determine if mutations in these genes influence the development of TB disease in humans. We already have a stored bank of DNA from tuberculosis patients and controls in Australia in which we have previously demonstrated that a single nucleotide polymorphism in the gene for the P2X7 receptor increases the risk of developing extrapulmonary tuberculosis. We are also setting up a collaborative project with Dr Linh in Vietnam to study the genetic control of TB in an highly endemic area, and we will begin this arm of the project focusing on the genes identified by our murine screens. These studies will increase significantly our understanding of how the immune system controls TB infection and to identify mutations in genes that are associated with the development of active tuberculosis disease. The use of both murine and human models allows us greater flexibility to characterize the mechanism of action of these genes and determine their involvement in the development of human TB.
Techniques to be used include:
The opportunity ID for this research opportunity is 104