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.
Stem Cell Based Strategies For Re-establishing T Cell Immunity In Aging And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$845,777.00
Summary
The thymus is the organ responsible for producing T cells, a key cell type in the body’s immune system. Certain cancer treatments damage the thymus, compromising the immune system and leaving patients susceptible to opportunistic infections. This proposal will develop clinically applicable strategies for generating functional human thymic mini-organs that could eventually help restore the immune system of people receiving treatment for cancer.
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.
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.
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.
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.
The Predictors Of Asthma And Lung Function Deficits In The Third Decade: Longitudinal Study Of MACS Sibships
Funder
National Health and Medical Research Council
Funding Amount
$1,176,908.00
Summary
This will be the world’s first birth cohort study to use substantial prospective data to investigate how biological, psychosocial, and environmental markers from birth will predict asthma and lung function in the third decade of life. Our findings will be crucial to the development of new policy and practice for the prevention and management of these conditions and uncover crucial risk factors for young adult asthma.
A specialised set of T lymphocytes called Mucosal Associated Invariant T (MAIT) cells react against bacteria and yeast, and reside at mucosal sites where the body's immune defences are most easily breached, e.g. respiratory tract and intestinal mucosa. This study investigates the role of MAIT cells in both protection and pathology in bacterial infections. Controlling MAIT cells could help in treating these conditions.
The Unique Nature Of Gamma Delta T Cell Recognition Resolved Through Interaction With H2-Q10
Funder
National Health and Medical Research Council
Funding Amount
$699,031.00
Summary
The liver is important for both digestion and immunity. Given these opposing functions, the liver must exert control points that prevent the immune system from recognising food products. We have now identified a new molecular target that controls the development of immune cells in the liver.