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The Molecular Determinants Of Immunological Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$473,477.00
Summary
Autoimmune diseases, such as type I diabetes and multiple sclerosis, are debilitating disorders that impose a massive toll on wellbeing in Australia and worldwide. This fellowship will support research aimed at determining the genes and mechanisms that control autoimmunity. New technologies will be brought to bear to track immune cells throughout their development, maturity and malfunction in disease settings. We aim to uncover new therapeutic targets to prevent and reverse autoimmune disease.
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.
Targeting Caspase 8 In T-Cell Homeostasis And Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,215,780.00
Summary
Chronic infectious diseases such as HIV, hepatitis B and tuberculosis impose a massive global health burden and new treatments are desperately needed. This proposal investigates a new approach to improve immune responses and clear chronic infections. Our multidisciplinary team will define the molecular and cellular biology underlying this approach and translate our findings by re-purposing a drug already approved for other indications in humans.
Tolerising Antigen-specific Immunotherapy For Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$1,395,549.00
Summary
We have developed a new immunotherapy to treat the underlying causes of type 1 diabetes (T1D) while leaving the rest of the immune system intact. To use this in patients, we need better tests to know when immune therapy is working. We will develop new methods to design the therapy and tools to track the relevant immune cells in T1D that work in variable patient groups. The knowledge gained will speed the pace of development and increase the chance of success of immunotherapy in T1D.
The Cell Death Mechanisms That Control Regulatory T Cell Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$583,782.00
Summary
A central question in immunology is how to prevent destructive immune responses (e.g. autoimmune disease) and initiate productive immune responses (e.g. against cancer). A major breakthrough in this area was the discovery of special immune cells, called a Regulatory T Cells. We propose to discover the genes that determine whether these cells live and die. We will use this information to control appropriate numbers and function of Regulatory T Cells to modify the immune system.
Male-female Sperm Signalling - A Novel Pathway For Peri-conceptual Health?
Funder
National Health and Medical Research Council
Funding Amount
$674,920.00
Summary
This project will investigate a new biological process in reproduction, whereby sperm delivered to the cervix at coitus transmit signalling molecules called microRNAs that influence the female immune response, to increase the chances of conception and pregnancy. We will define the molecular details of this signalling pathway in mouse models, and then determine whether human sperm have a comparable function in ‘priming’ the female body to conceive.
MicroRNA Networks That Safeguard The Functional Program Of Regulatory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$457,941.00
Summary
A newly discovered group of molecules termed microRNAs are thought to function as rheostats for the activity of genes. We have shown that these molecules are critical for the function of an immune cell type termed regulatory T cells. Without these cells, the immune system is unable to prevent uncontrolled and destructive inflammation. This proposal aims to utilize diverse technologies to uncover the precise molecular mechanisms by which microRNAs safeguard the function of regulatory T cells.
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.
Protecting Against Malaria Through Liver-resident Memory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,196,853.00
Summary
We have shown that formation of liver-resident memory T cells (Trm), a newly discovered type of immune cells, can be induced by an innovative vaccination strategy called prime and trap for highly efficient protection against malaria in mice. Here, we will enhance prime and trap vaccination efficacy by defining the conditions that maximize liver Trm-mediated protection and will characterize simian and human liver Trm cells, paving the way to create the most efficient human malaria vaccine to date