Role Of The CD8-Heparan Sulfate Interaction In CD8+ T Cell Development And Function
Funder
National Health and Medical Research Council
Funding Amount
$649,135.00
Summary
The immune system can recognise a large array of foreign pathogens without reacting to self-components. For this to occur T cells, the main mediators of immunity, must be made to tolerate self-molecules as they develop in the thymus. We have identified a novel interaction between a molecule called CD8 on T cells and a complex carbohydrate called heparan-sulfate, which helps auto-reactive T cells to be eliminates in the thymus. The aim of this project is to further investigate this phenomenon.
This project will investigate the factors that regulate the development and maintenance of a recently identified population of white blood cells called MAIT cells. MAIT cells are abundant in humans yet poorly understood. A better understanding of how these cells are regulated, and how they can be targeted in diseases, is necessary if we want to ultimately use these cells for immunotherapy.
Understanding the immune response is proving extremely complex and promising results for disease treatments from animal models are often difficult to translate to new clinical therapies. My research is unearthing weaknesses in our current knowledge of the immune system and seeking to replace them with a foundation that can exploit new developments in computer modelling and systems biology. In this way I aim to rationally manipulate the immune response.
Melanoma is a devastating disease. We are investigating new ways to treat and cure this form of cancer. Specifically, we are identifying how the body’s immune system interacts with melanoma and exploring new ways to use one’s own immune cells to destroy the cancer. This is achieved by understanding the interplay between various immune cells during melanoma and current therapies. This knowledge allows us to manipulate the immune cells providing better treatment.
Understanding The Complexity Of Antigen Presentation
Funder
National Health and Medical Research Council
Funding Amount
$774,540.00
Summary
I have developed and established the use of mass spectrometry to identify and quantitate ligands of antigen presenting molecules to understand the breadth of immune responses in a variety of human disease states including autoimmunity, cancer, infection and allergy. By embedding the technology in disease focussed research programs I will define the molecular bases of these diseases and the important immunological targets that will provide new avenues for therapeutic development and vaccines.
Host-virus Interactions That Define The Outcome Of Anti-viral T Cell Responses: Relevance To Viral Persistence
Funder
National Health and Medical Research Council
Funding Amount
$487,500.00
Summary
Infection with human cytomegalovirus (hCMV) is normally resolved without symptomatic evidence of infection. However, severe hCMV disease can occur in immunocompromised patients in which the manifestations of disease include chorioretinitis, interstitial pneumonia and hepatitis. In immunologically immature children, congenital infection results in cytomegalic inclusion disease (CID). CID in infants causes severe neurological sequelae resulting in mental retardation, deafness and blindness. Vaccin ....Infection with human cytomegalovirus (hCMV) is normally resolved without symptomatic evidence of infection. However, severe hCMV disease can occur in immunocompromised patients in which the manifestations of disease include chorioretinitis, interstitial pneumonia and hepatitis. In immunologically immature children, congenital infection results in cytomegalic inclusion disease (CID). CID in infants causes severe neurological sequelae resulting in mental retardation, deafness and blindness. Vaccination against hCMV induced cytomegalic inclusion disease has been designated Level I (most favourable) due to the prediction that it could save lives and prevent life-long disability. Given the essential nature of CD8 T cells in CMV control and the high prevalence of CMV in society, it will be crucial to develop a vaccine capable of eliciting an efficacious T cell response which develops lasting memory. We hypothesise that mCMV has evolved mechanisms for generating an appropriate T cell response involved in viral control and the establishment of a persistent infection. The central aim of the work in the current proposal is to investigate the cellular and viral mechanisms involved in the generation of cytomegalovirus specific T cells. The proposed studies will improve our understanding of the generation of anti-viral T cell responses and hence will be relevent to further our understanding of the role of T cells in human infection. More importantly the results will provide critical insights into the rational design of suitable antiviral drugs and vaccines.Read moreRead less
Molecular Regulation Of Tim3 Signalling In T Cells
Funder
National Health and Medical Research Council
Funding Amount
$366,252.00
Summary
Chronic inflammatory diseases like multiple sclerosis and cancer can be rectified via interventions of T cell checkpoint pathway. Tim3 is a T cell checkpoint molecule that is gaining extreme interest in these diseases. Here, we aim to identify molecular mechanism(s) to suppress or enhance Tim3 signalling in effector T cell, potentially leading to the development of therapeutic intervention to treat autoimmune disorders and cancers.
Multiple Paths Of TFH Differentiation And Their Impact On B Cell Protection Against Infection
Funder
National Health and Medical Research Council
Funding Amount
$923,466.00
Summary
Collaboration between T and B cells is crucial for immune protection and underpins current vaccine strategies. We have revealed an unappreciated flexibility that exists in T cell responses which varies the instructions they give B cells. It is likely this tailors immune responses to ensure protection to countless infectious diseases. This project uses cutting-edge technologies to understand this flexibility and has important implications for vaccine design and treatment of infectious disease.