Project Description

Dr Justine Mintern

The University of Melbourne

Designing effective vaccines

Advanced microscopy analysis and modelling

Friday 6 July 2018

Dr Justine Mintern heads the Vaccine Biology laboratory in the Department of Biochemistry and Molecular Biology at the University of Melbourne and the Bio21 Molecular Science and Biotechnology Institute. Justine’s research dissects the molecular pathways involved in promoting effective immunity. Her research uses cell biology, molecular biology and immunological approaches to uncover fundamental mechanisms of how an immune response is initiated. Major research projects include the investigation of dendritic cell biology, understanding immunity to infection and the design of effective vaccines. Justine completed her PhD at Walter and Eliza Hall Institute and undertook postdoctoral research at Harvard Medical School (Boston, USA) and the Whitehead Institute for Medical Research (Boston, USA) before returning to The University of Melbourne to head her own laboratory.

Dr Justine Mintern and her research team investigate how an immune response begins. Research encompasses understanding the fundamental biology of immunity through to advancing innovative vaccine design. Specifically, the Mintern laboratory analyse the biology of dendritic cells and how these cells use pathways of intracellular trafficking to generate cytotoxic and helper T cell immunity. This involves analysis of endocytosis, recycling, ubiquitin-mediated trafficking and autophagy and the trafficking machinery involved. The Mintern laboratory also exploits dendritic cell biology to advance vaccine technology by testing the potential of nanoparticles as vaccines in settings of immunity and infection.

Receptor-targeted vaccination employs a new strategy of vaccine design whereby vaccine antigen is targeted directly to dendritic cells. Dendritic cells are the specialised cell type that initiate immune responses and receptor-targeted vaccination ensures efficient delivery of vaccine antigen. The approach involves antigen being conjugated to an antibody that is specific for a given receptor at the surface of dendritic cells. Currently there is no consensus as to which receptor/s are the optimal targets for effective receptor-targeted vaccination. Here, we aimed to identify parameters that promote effective receptor-targeted vaccination. To do this, we made use of DNA-based fluorescence internalisation probes (FIP). These probes are designed to enable definitive measurements of receptor and/or ligand entry to the inside of cells. FIP measurements were undertaken by flow cytometry to obtain assessment of the endocytic patterns of individual dendritic cell receptors. We used FIP analysis to ask whether receptors that deliver more vaccine antigen to the interior of dendritic cells are superior in promoting enhanced immunity to vaccine antigen. This presentation will discuss outcomes of FIP analysis and discuss recent research combining FIP with CRISPR/Cas9 based screens.