This application seeks information on the factors controlling T cell survival, tolerance and responsiveness to foreign antigens and tumour antigens. Particular attention will be directed to determining how T cells are kept alive through contact with self ligands and cytokines while preserving self tolerance and how anti-tumour responses can improved without augmenting the function of T regulatory cells.
Cancer immunotherapy by “checkpoint blockade” boosts the immune response and leads to tumour rejection in some patients. To improve immunotherapy, information will be sought on the capacity of membrane vesicles prepared from dendritic cells (DC) to stimulate immune cells (T cells) in mice and elicit tumour rejection. Experiments are proposed to trace the fate of the vesicles after injection and improve tumour rejection by combination with checkpoint blockade and addition of cytokines.
Lodging Resident Memory T Cells Along The Respiratory Tract As An Approach To Protect Against Influenza Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$626,555.00
Summary
We have developed methods to deposit highly protective influenza fighting cells along the respiratory tract and we will apply these principles to develop better influenza virus vaccines
I am an immunologist determining the development and function of the dendritic cell system, including its role in autoimmunity and resistance to infection.
Molecular Pathways That Control Differentiation And Function Of Tissue-resident Memory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$890,636.00
Summary
T cells residing in organs such as gut, liver or skin guard against infection and are critical for preventing tumour development. We found that the combined activities of two factors, Blimp1 and Hobit, are critical for the development of these so-called tissue-resident T cells. Using a series of new tools, we will identify how the molecular network required for the development of tissue-resident T cell is established. This may allow us to harness their critical functions in therapy.
Molecular Regulators Of Adaptive Immunity To Overwhelming Viral Infections
Funder
National Health and Medical Research Council
Funding Amount
$786,898.00
Summary
Diseases caused by overwhelming viral infections, such as COVID-19, are associated with widespread impairments in immunity and constitute a major burden to human health. We have discovered that the molecule c-Myb is essential for the maintenance of immunity during chronic infection. In order to lay the foundations for novel and innovative anti-viral therapies, this project will dissect the molecular pathways regulated by c-Myb that maintain immunity during severe or chronic infection.
Our bodies rely on the production of potent, or ‘high affinity’, antibodies to fight infection. We have found that antibody responses are unexpectedly boosted following the depletion of a specific subset of immune cells. This is especially true for B cells that are poor antibody producers. Our findings are likely to be relevant to (1) the design of vaccines to infectious agents that have important CTL and antibody components (e.g. HIV), (2) for the improved production of antibody for therapeutic ....Our bodies rely on the production of potent, or ‘high affinity’, antibodies to fight infection. We have found that antibody responses are unexpectedly boosted following the depletion of a specific subset of immune cells. This is especially true for B cells that are poor antibody producers. Our findings are likely to be relevant to (1) the design of vaccines to infectious agents that have important CTL and antibody components (e.g. HIV), (2) for the improved production of antibody for therapeutic use (e.g. cancer).Read moreRead less
Protecting Against Malaria Through Liver-resident Memory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,196,853.00
Summary
We have shown that formation of liver-resident memory T cells (Trm), a newly discovered type of immune cells, can be induced by an innovative vaccination strategy called prime and trap for highly efficient protection against malaria in mice. Here, we will enhance prime and trap vaccination efficacy by defining the conditions that maximize liver Trm-mediated protection and will characterize simian and human liver Trm cells, paving the way to create the most efficient human malaria vaccine to date