Investigating The Potential Effect Of A Novel Immune Regulator (JET) In Preventing Graft Versus Host Disease
Funder
National Health and Medical Research Council
Funding Amount
$82,895.00
Summary
Graft Versus Host Disease (GVHD) is the primary complication of bone marrow transplants, in which the donor T-cells react with the recipient’s cells causing organ damage. Current treatments are not specific and cause further health problems. This research aims to test the therapeutic potential of a newly discovered molecule (JET) in treating and preventing GVHD. If successful, JET has the potential for treating other conditions such as rheumatoid arthritis, multiple sclerosis and miscarriages.
Investigation Of Dendritic Cell Activation And Function In A Murine Model Of Plasmodium And Schistosoma Co-infection
Funder
National Health and Medical Research Council
Funding Amount
$358,938.00
Summary
Malaria is responsible for over 2 million deaths annually, mainly in sub-Saharan Africa. Importantly, around 1 billion people in malaria endemic areas are infected with parasitic worms, thus malaria and worm co-infections frequently occur. This project will investigate how malaria and worm parasites interact to influence the immune response and clinical outcomes of each other in a mouse infection model. This will provide new strategies for the design of effective treatments in co-endemic areas.
The Genetics Governing The Specificity Of T Cell Receptors For Peptide-MHC
Funder
National Health and Medical Research Council
Funding Amount
$303,828.00
Summary
T lymphocytes play a pivotal role in the immune system by recognising virus-infected tissue through the use of highly specific cell surface receptors. These T cell receptors (TCR) recognise viral peptides (p) presented by MHC molecules on the surface of virus-infected cells. For a TCR to be successfully triggered, it must lock onto an exact 3-dimentional pMHC match. In this way, any given TCR must simultaneously recognise both the viral peptide and the MHC presenting it. Such recognition must be ....T lymphocytes play a pivotal role in the immune system by recognising virus-infected tissue through the use of highly specific cell surface receptors. These T cell receptors (TCR) recognise viral peptides (p) presented by MHC molecules on the surface of virus-infected cells. For a TCR to be successfully triggered, it must lock onto an exact 3-dimentional pMHC match. In this way, any given TCR must simultaneously recognise both the viral peptide and the MHC presenting it. Such recognition must be sensitive and precise since a false positive could result in destruction of healthy tissue. There are a huge variety of TCRs and pMHCs, but there are only a few examples where the precise molecular interactions within the TCR-pMHC complex are known. Surprisingly, these studies have shown very limited consistency in the way the TCRs bind the pMHCs and therefore, the structural rules that underlie why TCRs consistently bind MHC remains a mystery of critical importance to this fundamental feature of the immune system. In this proposal, we will attempt to elucidate the rules of TCR-pMHC engagement. Another question to be addressed in this proposal is: During a viral infection, why are certain TCRs chosen above others that also have the capacity to recognise the same viral peptide? By investigating exactly which feature-s of these receptors predisposes their supremacy, we may be better able to predict the outcome of a pathogen attack and to even one day build our own super receptors. Finally, this proposal will also investigate how natural mutations in TCR genes across the human population affect our individual responses to viruses. Overall, advances in each of these core areas of medical research will aid in the development of new intelligent vaccines and individualised drugs for the treatment of cancer and infectious disease.Read moreRead less
Investigations Into The Biology And Functionality Of The Human T Cell Receptor
Funder
National Health and Medical Research Council
Funding Amount
$424,262.00
Summary
T lymphocytes play a pivotal role in the immune system by recognising virus-infected tissue and tumour cells through the use of specific cell surface receptors called T cell receptors (TCR). This project will study why partcular TCRs are used by the immune system, and will also examine the specificity of T cell recognition by determine the range of molecules an individual T cell can recognise. The work will aid in the development of new intelligent vaccines for cancer and infectious disease.
A Novel Strategy Targeting Quorum Sensing Molecules And Catalase Function To Block Pseudomonas Aeruginosa Lung Infection
Funder
National Health and Medical Research Council
Funding Amount
$451,118.00
Summary
Pseudomonas aeruginosa causes serious infections, particularly in those with Cystic Fibrosis, immunocompromise, serious burns or long term catheters. We will use a unique strategy to target virulence factors that will assist in clearing acute infection, prevent establishment of new chronic infections, and potentially reduce severity of established chronic infections. It has the potential to make antibiotic therapy more effective and lessen the extent of antibiotic therapy required.
Quorum Sensing Signal Molecule Modulation Of Immunity: Role In Host Responses To P. Aeruginosa Lung Infection
Funder
National Health and Medical Research Council
Funding Amount
$251,014.00
Summary
Pseudomonas aeruginosa is a bacterium that causes serious infections in humans, particularly those with Cystic Fibrosis, or who are immunocompromised, suffering serious burn injuries or have long term catheters. This study will investigate how P. aeruginosa may be able to increase its virulence by producing molecules known as Quorum Sensing Signal Molecules (QSSM). We believe the production of these QSSMs by this bacterium enables them to affect how the host responds by affecting their immune sy ....Pseudomonas aeruginosa is a bacterium that causes serious infections in humans, particularly those with Cystic Fibrosis, or who are immunocompromised, suffering serious burn injuries or have long term catheters. This study will investigate how P. aeruginosa may be able to increase its virulence by producing molecules known as Quorum Sensing Signal Molecules (QSSM). We believe the production of these QSSMs by this bacterium enables them to affect how the host responds by affecting their immune system. We will be investigating how this QSSM may suppress immunity and what influence this has on both the severity of infection and the potential for development of chronic infection. The study will first of all determine where the QSSM exerts its effects (that is, can it escape from the site of infection to affect other host sites) and this will direct us in how we may learn more about the way it can affect the host during an infection. We will investigate the direct affects of QSSM on acute and chronic types of P. aeruginosa lung infection and then from this, determine if the outcome exacerbates a subsequent infection. The work is significant in that a knowledge and understanding of these virulence factors will assist in the design of better therapeutic and prophylactic strategies for both prevention of infection in susceptible individuals and treatment of those that suffer from chronic infection.Read moreRead less
The aim of this project is to develop mathematical models and computer software capable of predicting immune responses to infection and disease. This “artificial immune system” should lead to improved vaccine design and better understanding of what causes the immune system to attack its own body, causing autoimmune disease, or fail to respond, causing immunodeficiency. This enabling science could then lead to improvements in treatment for a range of conditions of clinical importance.