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.
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.
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
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.
Functional Dyspepsia: Characterisation Of The Immunopathology And Testing A Novel Therapeutic Strategy.
Funder
National Health and Medical Research Council
Funding Amount
$739,604.00
Summary
Dyspepsia, unexplained stomach discomfort and pain, is a common and costly problem; few effective treatments exist and the causes are unknown. We have found that the numbers of a type of immune cell, the eosinophil, are increased in the top of the small bowel in patients with dyspepsia. This study will explore the mechanisms that lead to increased eosinophils and then test the effectiveness of a treatment to suppress this overactive immune response which could rapidly change clinical practice.
Development And Validation Of A Latent Tuberculosis Diagnostic
Funder
National Health and Medical Research Council
Funding Amount
$534,865.00
Summary
Globally, tuberculosis is a leading cause of death with 9.6 million new diagnoses in 2014. The diagnosis of latent TB infection is important, but is difficult to make because current assays are suboptimal. We have developed a very simple assay which detects responses to TB antigens by co-expression of two surface markers expressed by CD4+ T cells. We propose to develop this into a highly standardised kit for the diagnosis of TB with our commercial partner Cytognos.
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 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.
How Does NF-kB2 Regulate Thymic Selection To Prevent Organ-specific Autoimmune Disease?
Funder
National Health and Medical Research Council
Funding Amount
$787,600.00
Summary
Autoimmune diseases like type 1 diabetes and thyroiditis arise from defects that cause the immune system to confuse self and non-self. Normally, this distinction is programmed in the thymus. We recently identified the gene that causes a form of autoimmune disease. We also made an important discovery about how the thymus gland regulates self-non-self discrimination. We will build on these two discoveries to gain a precise understanding of how the immune system normally avoids autoimmune disease.