Viral Immunology
Our lab is focused on understanding viral infections by viruses that are a health burden. Trying to understand why some of us are at higher risk of developing severe infection due to those virus, while other seems to be able to handle the virus and have an immune system allowing them to control the infection.
Our Research on SARS-CoV-2 Virus
As our lab is focused on viruses, since 2020 we have re-focused a part of our research effort to study the new SARS virus responsible for COVID-19, and start studying the immune response to SARS-CoV-2 and its variants. We work in collaboration with other teams in Australia and overseas to fully dissect the T cell, B cell and Antibody responses toward the virus. We aim to map and characterise in depth SARS-CoV-2 peptides able to stimulate T cells in better understand the progression of the disease, the role of T cell in COVID-19. Mapping epitopes activating T cells and characterising their molecular features help understand how the immune system molecule, called HLA, are presenting the epitopes. This information can help anticipate or predict which mutation will be an issue for T cell recognition, as well as quickly assessing the impact on the immune system, and immune protection, that new SARS-CoV-2 variants might have.
As part of our research on COVID-19 we also ask the help from our community to participate into our biobank of blood samples. We are currently recruiting volunteers to give blood after infections or vaccination, there is no restriction to participate other than been over 18 years old and able to give blood.
If you are interested in taking part in our study please fill up the information in this link or scan the QR code below.
Our research on Influenza Virus
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.
Our research on HIV virus
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.
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.
Structural Immunology
Our lab use X-ray crystallography to gain an understanding of the relationship between the immune cells presenting the pathogens (APC or antigen presenting cell) and the ones that are responsible to recognise them (T cells). The advantage of crystallography and structural biology, is that we can visualise the atomic details of the molecules involved in such interaction. This give us an idea of what part of each molecule is important and this information can be used to manipulate and modify the interaction.
To be able to generate atomic structure, which are 3D models, of our molecules, we need first to produce the proteins in large quantity, purify them to a very high level, then crystallise them. Similarly to the salt crystals on our kitchen table, but way smaller, we are producing crystals with our proteins.
Structural biology has provided science with a powerful tool to observed the very fine details of protein and small molecules interaction, for example to understand how a small drug act and interact with its specific target.
Collaboration
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.