Structural And Functional Investigation Of Killer-Cell Immunoglobulin-like Receptors
Funder
National Health and Medical Research Council
Funding Amount
$546,966.00
Summary
Natural Killer (NK) cells are an important component of the immune response to cancer and infection. This project will define the molecular targets that are recognised by NK cells. This knowledge can then be used as a guide in the selection of bone marrow donors in the treatment of leukaemias as well as understanding how we fight infections.
Development, Regulation And Role Of Innate Immunological Memory In Malaria
Funder
National Health and Medical Research Council
Funding Amount
$563,860.00
Summary
Innate immunity is traditionally considered to be a short-lived, non-specific first line of defense against pathogens. However, recent reports suggest that innate immune cells can learn from previous pathogen encounters, resulting in enhanced responses on repeat infections with the same pathogen. We will study the role and regulation of innate immunological memory during malaria infection. This will advance our understanding of malaria immunology and will likely aid in the development of vaccine ....Innate immunity is traditionally considered to be a short-lived, non-specific first line of defense against pathogens. However, recent reports suggest that innate immune cells can learn from previous pathogen encounters, resulting in enhanced responses on repeat infections with the same pathogen. We will study the role and regulation of innate immunological memory during malaria infection. This will advance our understanding of malaria immunology and will likely aid in the development of vaccines.Read moreRead less
Identification Of CIS As A Potent Checkpoint In NK Cell-mediated Tumour Immunity
Funder
National Health and Medical Research Council
Funding Amount
$959,596.00
Summary
Cancer must evade detection by the immune system in order to develop. Natural Killer (NK) cells can detect and kill cancer cells. We have discovered a potent "checkpoint" in the NK cell activation pathway that desensitises NK cells to growth factors and switches off their activation and killer function. When this checkpoint is inhibited, NK cells are super activated and can prevent most types of cancer metastasis in mice. Targeting this checkpoint in humans could revolutionise cancer therapy.
Structural And Functional Characterisation Of The Killer Cell Immunoglobulin-like Receptor (KIR) Family Of Natural Killer Cell Receptors
Funder
National Health and Medical Research Council
Funding Amount
$348,070.00
Summary
Natural Killer (NK) cells are an important component of the immune response to cancer and infection. This project will define the molecular targets that are recognised by NK cells. This knowledge can then be used to guide in the selection of bone marrow donors in the treatment of leukemias as well as understanding how we fight off infections.
Do NK Cells Limit The Long Term Burden Of CMV In Older Australians And Transplant Recipients?
Funder
National Health and Medical Research Council
Funding Amount
$413,864.00
Summary
Most people are infected with cytomegalovirus at an early age. The virus is not naturally cleared from the body but becomes latent and may be reactivated by stress or inflammation. Repeated immune responses to these reactivations causes more inflammation and wears out the immune system resulting in diseases of aging (eg: cardiovascular disease). Here we investigate which aspects of the immune system can control CMV in healthy people and in renal transplant recipients. We focus on a population of ....Most people are infected with cytomegalovirus at an early age. The virus is not naturally cleared from the body but becomes latent and may be reactivated by stress or inflammation. Repeated immune responses to these reactivations causes more inflammation and wears out the immune system resulting in diseases of aging (eg: cardiovascular disease). Here we investigate which aspects of the immune system can control CMV in healthy people and in renal transplant recipients. We focus on a population of cells called natural killer (NK) cells.Read moreRead less
The liver is an important organ in terms of immune responses. Owing to its exposure to many antigens, it is required to maintain a form of immune tolerance. This ensures that overt immune responses which would damage the liver do not occur. One means by which tolerance occurs is through silencing killer cells through the regulation of molecules of Major Histocompatibility Complex (MHC). This project will explore the role of a soluble form of MHC which is expressed only in the liver.
Determining The Role Of DOCK8 In CD4+ T And B Cell Differentiation And Its Implications On Autosomal Recessive Hyper IgE Syndrome (AR-HIES)
Funder
National Health and Medical Research Council
Funding Amount
$512,600.00
Summary
Autosomal recessive hyper IgE (AR-HIES) syndrome due to mutations in DOCK8 is a rare primary immunodeficiency whereby patients present with susceptibility to severe and recurrent viral infections as well as an increased risk of developing cancer, severe food and environmental allergies, and atopic disease characterised by hyper IgE and extreme eosinophilia. This grant will investigate how abnormal DOCK8 function in CD4+ T cells and B cells contributes to disease pathogenesis in AR-HIES patients.
Mechanisms And Targets Of Antibody-complement Interactions That Neutralize Malaria
Funder
National Health and Medical Research Council
Funding Amount
$647,977.00
Summary
Our project aims to identify immune mechanisms that neutralize malaria from the moment of inoculation by a mosquito, before infection can become established to prevent the development of malaria disease. Furthermore, we will discover specific targets of protective immune responses. We expect this project will provide major new advances in our knowledge of human immunity to P. falciparum malaria, one of the world’s most significant causes of mortality and morbidity, and we will use this knowledge
An Investigation Into The Molecular Basis Of MAIT Cell Recognition Of Vitamin B Based Metabolites
Funder
National Health and Medical Research Council
Funding Amount
$883,762.00
Summary
Mucosal associated invariant T cells (MAIT cells) are an abundant T-cell population in humans, that is found mostly in the gastrointestinal mucosa. We have recently shown that MAIT cells can be activated by metabolites of vitamin B. This proposal will investigate how the MAIT cells "see" vitamin B metabolites. This research will pave the way for novel therapeutics that can modulate MAIT cell activity.
The Interplay Between Viperin, Peroxisomes And The Cellular Innate Antiviral Response
Funder
National Health and Medical Research Council
Funding Amount
$556,127.00
Summary
Infection with a virus initiates a cellular antiviral response that attempts to limit viral replication, however how this response is regulated is not well understood. In this proposal we will investigate a cellular protein (viperin) that can regulate this process by interaction with peroxisomes to amplify the antiviral response. This work will provide possible targets for therapeutic manipulation of the innate immune response that will be applicable to a wide range of viral infections.