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
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
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.
Characterisation And Targeting T Cellular Metabolism To Improve Control Of Chronic Viral Infections
Funder
National Health and Medical Research Council
Funding Amount
$791,427.00
Summary
CD8+ T cells are the frontline warriors of our immune system that can eliminate infected or cancerous cells. However, diseases caused by overwhelming viral infections are associated with widespread impairments in immunity and cellular metabolism. Here, we propose to examine molecular pathways involved in cellular metabolism that could be utilized to improve therapies against viral infection and cancer.
Viral Antigen Presentation Kinetics And Memory T Cell Inflation
Funder
National Health and Medical Research Council
Funding Amount
$503,753.00
Summary
The ageing of the population is one of the major transformations being experienced by Australia’s population which will have major health implications. Recent studies have shown that many elderly individuals display ‘immune risk phenotype’ (IRP) which is characterised by a severely distorted immune system and human cytomegalovirus (CMV) infection. In this project we will investigate the mechanisms by which CMV alters cellular immune system and thus impacts on the host immunity against other path ....The ageing of the population is one of the major transformations being experienced by Australia’s population which will have major health implications. Recent studies have shown that many elderly individuals display ‘immune risk phenotype’ (IRP) which is characterised by a severely distorted immune system and human cytomegalovirus (CMV) infection. In this project we will investigate the mechanisms by which CMV alters cellular immune system and thus impacts on the host immunity against other pathogens.Read moreRead less
The Role Of Kdm1a In Epigenetic Regulation Of Virus-specific T Cell Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$510,982.00
Summary
Recovery from infection, or vaccination, results in the establishment of protective immunity that persists for the life of an individual. Unfortunately, our understanding of how protective immunity is established and maintained after infection or vaccination is lacking. This proposal will determine whether specific enzymes involved in rewriting the genetic blueprint are key for establishing and maintaining this protective capacity. Understanding these mechanisms has implications for vaccination ....Recovery from infection, or vaccination, results in the establishment of protective immunity that persists for the life of an individual. Unfortunately, our understanding of how protective immunity is established and maintained after infection or vaccination is lacking. This proposal will determine whether specific enzymes involved in rewriting the genetic blueprint are key for establishing and maintaining this protective capacity. Understanding these mechanisms has implications for vaccination and improved immunotherapy strategies for cancer.Read moreRead less
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.