Structural investigation into T cell response to virus (flu and HIV)

Viruses and pathogens are part of day-to-day encounters that the immune system needs to deal with. How the immune system “sees”, recognises and eliminates viral infection is not fully understood. Indeed, viruses are able to mutate in order to escape the immune system surveillance. If we were to develop better vaccine and drugs, or even vaccine against viruses like HIV, it is essential to understand the mechanism of viral recognition and viral escape prior to this. PROJECT 1 (structural immunology) Viruses such as Influenza and HIV are able of high mutation rates and so more likely to escape the immune system surveillance; in addition they are both a health burden. We use X-ray crystallography to make 3D structures of viral peptides bound to immune system proteins (MHC molecule) in complex with T cell receptor (TCR). The atomic structure allows us to observed the details of the interaction between the peptide and the TCR. These structures help us understanding the recognition mechanism of the T cell for the viral particle. PROJECT 2 (cellular immunology) will be dissec0ng the magnitude, func0onal capacity and molecular characteris0cs of T cell responses towards novel influenza virus epitopes using a range of techniques including cell culture, flow cytometry and single-cell sorting and multiplex PCR.   Project will use biochemistry to produce the proteins: peptide-MHC and TCR, state-of-the-art crystallisation platform at Monash (Crystalmation Facility) to determine the crystallisation conditions, X-ray Synchrotron radiation at the Australian Synchrotron. We will also be using biophysical approach to determine affinity between the proteins, and cell culture, flow cytometry and single-cell sorting and multiplex PCR.