The Mezzanine T Cell Response: Intervening At The Coal Face
Funder
National Health and Medical Research Council
Funding Amount
$765,585.00
Summary
In an initial immune response, specialised cells in lymph nodes tell T cells to multiply; the stimulated T cells depart and enter target tissue (e.g. lung in the case of flu). We describe a new response whereby the target tissue itself can tell T cells to multiply further. This response in target tissues reveals a new way of altering immune responses. This is especially important as in many diseases, the primary lymph node response has already occurred, so cannot be therapeutically intervened.
The Calcium Channel TRPV4 In Skeletal Development And Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$683,069.00
Summary
We have discovered that mutations in a calcium channel gene, TRPV4, cause an inherited osteoarthritis in the hands and feet. This work suggests that TRPV4 may be important in osteoarthritis and suggests the exciting possibility that modulating TRPV4 activity may provide a new therapeutic approach for arthritis. We will study how and why the mutations disrupt channel function and study mouse models to see if they are more or less susceptible to arthritis.
Targeting Adenosine Mediated Immunosuppression To Enhance CAR T Cell Activity
Funder
National Health and Medical Research Council
Funding Amount
$633,447.00
Summary
The use of white blood cells genetically engineered to eradicate cancer cells specifically has been a major breakthrough in cancer treatment. These cells (CAR T cells) are very effective in blood cancers, but do not currently work well in other cancers. This is due to the immune suppressing nature of the cancer environment. I propose to use strategies to overcome this by genetically reprogramming the CAR T cells to be resistant to suppression by the cancer and therefore be more effective.
The Role Of Co-signalling Receptors In Cytotoxic Lymphocyte Activity During Infection And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$739,657.00
Summary
Cytotoxic lymphocytes (CLs) are immune cells that detect and kill cancer cells. CLs recognise ‘stress’ proteins on cancer cells through specialised receptors, and this provides the signal for them to kill. However, some cancer cells, such as leukemic cells, can interfere with this recognition to avoid killing by immune cells. This project will investigate the mechanism of recognition and killing of cancer cells by CLs, using both mouse models and cells from patients with acute myeloid leukemia.
Improving The Prediction And Detection Of Contributors To Term Stillbirth
Funder
National Health and Medical Research Council
Funding Amount
$570,358.00
Summary
Stillbirths are a global human tragedy, with 1 in 130 of all pregnancies in Australia ending in stillbirth. We propose to use ultrasound and blood markers to improve the detection of babies who are not growing well, a leading risk factor for stillbirth. Sleep position has also been associated with stillbirth, so we will study fetal heart rate responses during an overnight sleep study to see if breathing events overnight may be an important contributor to stillbirth in growth restricted fetuses.
Generation Of Protective Immunity Against Severe Influenza Disease In Indigenous Australians
Funder
National Health and Medical Research Council
Funding Amount
$1,630,970.00
Summary
Hospitalisation and death rates from influenza are high in the Indigenous population, especially when a new virus emerges. There is an urgent need for a vaccine that protects against all influenza strains. T cells recognising conserved viral regions elicit such protection. As T cells are restricted by proteins called HLAs, which vary across ethnicities, we will define T cell regions for HLAs prominent in Indigenous Australians and define how to generate protective immunity against influenza.
Understanding Influenza-specific T Cell Immunity In The Indigenous Population
Funder
National Health and Medical Research Council
Funding Amount
$870,112.00
Summary
Hospitalisation and death rates from influenza are high in the Indigenous population. There is an urgent need for one-shot universal vaccine that protects against seasonal and pandemic strains. T cells recognising conserved viral regions can elicit such protection. As T cells are restricted by proteins called HLAs, variable between different ethnicities, we will define T cell regions and their HLA restrictions in the Indigenous population to propose strategies for universal T cell-based protecti ....Hospitalisation and death rates from influenza are high in the Indigenous population. There is an urgent need for one-shot universal vaccine that protects against seasonal and pandemic strains. T cells recognising conserved viral regions can elicit such protection. As T cells are restricted by proteins called HLAs, variable between different ethnicities, we will define T cell regions and their HLA restrictions in the Indigenous population to propose strategies for universal T cell-based protective immunity and vaccine design against influenza.Read moreRead less
Methylation-sensitive T Cell Genes And Childhood Food Allergy.
Funder
National Health and Medical Research Council
Funding Amount
$461,232.00
Summary
Australia has the highest reported prevalence food allergy in the world. Despite this, little is known about how allergy develops. Mounting evidence implicates environmentally induced disruption of the genetic blueprint via a process known as epigenetics. We are combining the strengths of food challenge proven food allergy with assessment of immune functioning & cutting edge genomics, to extensively characterise the pathways leading to food allergy in children.
The Role Of Regulatory T Cells In Rapidly Progressive Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$581,113.00
Summary
Inflammation of the kidneys is an important, yet poorly understood cause of kidney disease in Australia. As part of our endogenous defenses against inflammation, we have cells called regulatory T cells that dampen inflammation and are protective. This project will define the role of some of these cells and examine potential ways to use them do dampen kidney inflammation.
The Mechanisms Of Epithelial Cell Survival That Govern Thymus Function
Funder
National Health and Medical Research Council
Funding Amount
$620,967.00
Summary
The thymus is an organ dedicated to the production of crucial immune cells, called T lymphocytes. Cancer treatments, such as radiation or chemotherapy, destroy thymic function and impair immune recovery in patients. We aim to uncover molecular processes that govern the life and death decisions of cells in the thymus. Our goal is to then use this information to develop treatments to protect this critical organ from damage and improve immune recovery following radiation or chemotherapy.