T Cell Biology Research Program
Lab head: Professor Barbara Fazekas de St. Groth
Location: Centenary Institute
Correlative microscopy to define how dendritic cells turn on T cells
Primary supervisor: Barbara Fazekas de St Groth
As well as expressing peptide-MHC complexes on their surface, dendritic cells export membrane-bound vesicles carrying high concentrations of peptide-MHC. We have discovered that these membrane-bound vesicles are the first source of peptide-MHC to be recognised by naive CD4 T cells. Long before DCs themselves reach the draining LN from an immunisation site, they have showered the node with peptide-MHC-carrying vesicles that activate the highest affinity anti-peptide T cells and cause them to move retrogradely through the node to the DC entry site. This mechanism speeds up the process of screening the T cell repertoire so that all the T cells present in the node can be screened within the first 18-24hours of the response.
In this project you will determine the exact nature of the membrane-bound vesicles exported by DCs. There are 2 possibilities: microparticles and exosomes, which have quite distinct molecular and morphological characteristics. Using correlative microscopy to superimpose fluorescent and scanning electron microscopy images of DCs expressing a green fluorescent protein-tagged MHC class II molecule, you will follow the process of vesicle formation, export and recognition by T cells. This will be the first time that such a process has been visualised.
The project will have 2 supervisors: Prof Barbara Fazekas, T Cell Biology at Centenary Institute, and Prof Filip Braet, Sydney Microscopy and Microanalysis (SMM) at the University of Sydney. Although no previous microscopy experience is required, the student will need both an interest in, and a talent for, microscopy, as most of the year will be spent performing this technique, using the new super-resolution microscope and transmission em at the SMM. The project will also involve tissue culture of murine dendritic cells and T cells.
Discipline: Infectious diseases and Immunology
Co-supervisors: Filip Braet
Keywords: Dendritic cells, Microscopy/Immunohistochemistry, T-cells