Gras Lab research
About Associate Professor Stephanie Gras
Stephanie is an NHMRC Senior Research Fellow in the Department of Biochemistry and Molecular Biology within the Biomedicine Discovery Institute. She's a structural biologist who specialises in viral immunity. With colleagues at Monash University and the Peter Doherty Institute at the University of Melbourne and overseas, she is studying how the immune system handles viral infections such as influenza and HIV, and conducting fundamental research to improve the development of new therapeutics and vaccine.
1. Structural investigation into T cell response to Influenza virus (Flu)
Influenza viruses cause significant morbidity and mortality worldwide. Although a vaccine is available, it primarily induces a humoral response and requires updating annually. Additionally, the vaccine provides protection if the predicted strains match the circulating strains, but sometimes the virus mutate away from the prediction and the vaccine will have minimal benefit. As such, there is a need and effort to develop a universal influenza vaccine that could provides long-lasting protection against distinct influenza strains throughout global populations. This will allow a one-short vaccine to be developed, that would protect against multiple strains of the virus without the need of having to predict every year, or having to update the vaccine and get the “jab” every year as well. Our immune system is arm of cells called CD8+ T cells that are known to be protective against influenza disease, decreasing the quantity of virus (viral load) and disease severity.
Our aim is to understand how we can isolate T cells that would be protective, what are their characteristics, and provide the information to understand how we can specifically activate those cells.
Our lab has multiple projects focused on understanding the influenza virus immunity:
- Understanding how some T cells are able to recognise multiple mutations within the same epitope, enabling the immune system to protect us against different flu strains.
- Discovering new flu epitopes that are activating potent T cells across individuals with different genetic backgrounds.
- Determining the mode of action of drugs that target influenza.
2. Structural investigation into T cell response to Human Immunodeficiency Virus (HIV)
Our aim is to understand how HIV controllers T cells are protective, their functional but also molecular features, that could provide some information for new therapeutic avenues.
While antiretroviral therapy (ART) has dramatically improved the health of HIV-infected individuals, comorbidities associated with persisting inflammation (e.g. cardiovascular disease, osteoporosis, cancer) have emerged as important complications. It is unquestionable and imperative to develop new treatments (and ideally, a vaccine) for this virus. Therapeutics or vaccine that could control HIV would therefore help avoid damage by comorbidities.
Unfortunately, there are major hurdles imposed by HIV (i.e. high mutation and replication rates creating tremendous viral diversity and the latent HIV reservoir established after infection) that are difficult to overcome.
To tackle these issues, our work will focus on a subset of individuals – named controllers – known to control HIV infection and/or delay disease progression. Although HIV infection impacts on multiple facets of the immune system (including T cells, Natural Killer cells, Treg cells, among others), the strongest genetic links to HIV control shown to date have been the expression of specific “protective” human leukocyte antigen (HLA) molecules and their associated potent T cell responses. Thus, understanding such superior T cell responses at the molecular level—specifically, the interaction between HIV peptides presented by HLA complexes and T cell receptors —is central for informing therapeutic or vaccine development against HIV.
Visit Associate Professor Gras' Monash research profile to see a full listing of current projects.
- T cells
- Structural Immunology
Figure 1. Protein Purification A. Gel Filtration chromatography, B. SDS PAGE
Figure 2. X-ray protein diffraction pattern
Figure 3. TCR-peptide-HLA complex structure
Figure 4. Multiplex PCR for TCR α and β chain amplification after single cell sorting
Figure 5. TCR repertoire analysis of T cell clones
Figure 6. Single cell sorting from HIV+ donors
Figure 7. SPR sensograms and affinity curves for a TCR-peptide-HLA complex (WT HLA vs mutant R79A HLA)
We also collaborate with different groups on diverse projects related with immunology and/or structural biology. Our expertise in biochemistry, protein assay, immunology and structural biology can be beneficial to explore different field and help answer different questions. Click on the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).
Student research projects
The Gras Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short term research opportunities available.
Please visit Supervisor Connect to explore the projects currently available in our Lab.