Understanding Pathogenicity And Immunity In An Encephalitic Mouse Model Of Hendra Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$572,342.00
Summary
Our understanding of Hendra virus infection and immunity is extremely limited and has been hampered by a lack of appropriate animal models of disease and reagents. This Project will employ a newly-established mouse model to study encephalitis, the most life-threatening manifestation of this infection. We will use unique, state-of-the-art infrastructure and a plethora of mouse-specific reagents to investigate the mechanisms involved in regulating the host response to infection.
IL-2-anti-IL-2 Complexes In Immunity To Blood Stage Malaria Infection And Prevention Of Cerebral Immunopathology
Funder
National Health and Medical Research Council
Funding Amount
$586,428.00
Summary
Cerebral malaria is a severe complication of malaria infection, which accounts for a large proportion of malaria-related deaths each year. There is no vaccine against malaria licensed for use in humans. Trial vaccines have been shown to protect poorly against cerebral malaria, and have on occasion, increased the its incidence amongst experimental animals. We aim to develop a safe malaria vaccine that controls malaria parasite numbers in the body, and also prevents cerebral malaria.
CD4 T cell programming by neonatal and early-life infection. T lymphocytes (T cells) are white blood cells that play a critical role in protecting the body from infection. Before T cells can function they need to be programmed so that they can specifically respond to an infectious agent (a type of bacteria or virus). Inappropriate programming can lead to disease. Whether T cells respond to an infectious agent or foreign substance in a protective or destructive manner may critically depend on the ....CD4 T cell programming by neonatal and early-life infection. T lymphocytes (T cells) are white blood cells that play a critical role in protecting the body from infection. Before T cells can function they need to be programmed so that they can specifically respond to an infectious agent (a type of bacteria or virus). Inappropriate programming can lead to disease. Whether T cells respond to an infectious agent or foreign substance in a protective or destructive manner may critically depend on the age that an individual first encounters the infection. Our project will identify critical periods in life that direct T cell programming to subsequent protective or destructive responses, providing new insights into the developing immune system that may be exploited to treat disease or develop vaccines.Read moreRead less
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.
Identification of novel markers of inflammation. This project will benefit Australia as it will increase basic understanding of inflammatory processes, result in a new generation of diagnostics for inflammatory diseases that could lead to earlier diagnosis and to monitor treatment, resulting in large economic and health benefit. It may lead to development of novel new therapies using monoclonal antibodies to regulate processes in immune, cardiovascular and infectious diseases. The work will gene ....Identification of novel markers of inflammation. This project will benefit Australia as it will increase basic understanding of inflammatory processes, result in a new generation of diagnostics for inflammatory diseases that could lead to earlier diagnosis and to monitor treatment, resulting in large economic and health benefit. It may lead to development of novel new therapies using monoclonal antibodies to regulate processes in immune, cardiovascular and infectious diseases. The work will generate significant economic spin-offs to the Australian biotechnology industry and will further relationships and training between research and development.Read moreRead less
Understanding The Role Of Innate Immune Cells In Regulating Gut-associated Lymphoid Tissues At Steady-state And In Disease
Funder
National Health and Medical Research Council
Funding Amount
$365,126.00
Summary
The intestine is the largest surface area forming a protective barrier between the external environment and the body. It represents the first line of defence against invading pathogens. The immune system of the intestine is critical to protect this tissue -any breakdown leads to profound and progressive inflammatory disease of the gut such as chronic inflammatory bowel disease. Our work will determine the critical the mechanisms that protect the gut opening the door to targeted intestinal immuno ....The intestine is the largest surface area forming a protective barrier between the external environment and the body. It represents the first line of defence against invading pathogens. The immune system of the intestine is critical to protect this tissue -any breakdown leads to profound and progressive inflammatory disease of the gut such as chronic inflammatory bowel disease. Our work will determine the critical the mechanisms that protect the gut opening the door to targeted intestinal immunotherapeutics.Read moreRead less