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.
A Novel Molecular Mechanism Controlling Myelopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$878,439.00
Summary
The immune system is comprised of many different cell types, each with a specialised function. Many are short-lived and must be continually replenished throughout life. Abnormalities in this process underlie many human diseases, including immunodeficiency, autoimmunity and cancer. We have discovered a novel molecular mechanism that is critical for the production of immune cells. This project will investigate how this mechanism is controlled and the impacts on myelodysplastic syndromes.
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.
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.
Controlling Life And Death Of Dendritic Cell Subsets For Immunomodulation
Funder
National Health and Medical Research Council
Funding Amount
$639,577.00
Summary
Dendritic cells are pivotal in orchestrating immune responses; for example, they can turn immune cells into assassins to kill virus infections. Their function is so diverse that different dendritic cells do different jobs. There are many genes that control life and death of cells but those that are important for each specialised dendritic cell have not been comprehensively studied. Drugs that affect the proteins made by such genes selectively may be a new way of controlling immune responses.
Signaling Pathways To Enhance Potency Of AMPK-targeting Drugs
Funder
National Health and Medical Research Council
Funding Amount
$661,966.00
Summary
Sedentary lifestyles and consumption of high energy foods has led to epidemics of obesity-related metabolic diseases that place enormous financial and medical burden on the Australian economy. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK) which functions as both a cellular fuel gauge and co-ordinator of whole-body metabolism. Our goal is to improve AMPK drug potency by identifying novel processes that sensitize AMPK to drugs.
Do Exposures Before Conception Influence The Risk Of Asthma In Offspring?
Funder
National Health and Medical Research Council
Funding Amount
$688,586.00
Summary
Asthma and poor lung function are major causes of public health issues. Emerging evidence suggests adverse exposures even before the conception of a child may cause these conditions. The proposed project is part of an international study across generations to identify these factors. This study will provide novel evidence to guide interventions and identify studies to advance this area further. These original findings will be of great importance both nationally and internationally.
Clinical Trial Of A Suprachoroidal Visual Prosthesis For The Profoundly Vision Impaired
Funder
National Health and Medical Research Council
Funding Amount
$1,098,802.00
Summary
For 15 years we have been designing a bionic eye. We have made a device called the Phoenix99 and shown in short term animal tests that it is both safe to implant but also that it potentially performs better than any other device in the world. We are requesting funds to complete longer term animal testing of the device and then commence a small human clinical trial to demonstrate the benefits of the technology – specifically that it is able to help blind people navigate without assistance.
Functional Electrical Stimulation Assisted Cycling (eStimCycle):A Novel Intervention To Improve Outcomes In The Critically Ill
Funder
National Health and Medical Research Council
Funding Amount
$868,811.00
Summary
The legacy of critical illness leaves millions of survivors worldwide with long lasting deficits in physical and brain function as well as anxiety, depression and post-traumatic stress disorder. Early rehabilitation may prevent or minimise these effects. This study evaluates the effectiveness of functional electrical stimulation of muscles with assisted in-bed cycling (eStimCycle) on muscle bulk, strength, physical and brain function at hospital discharge, 6 and 12 months.
M-PreM Study: Reproductive Factors, From Menarche To Pre-menopause, And The Risk Of Cardiometabolic And Respiratory Conditions Before Menopause
Funder
National Health and Medical Research Council
Funding Amount
$1,366,831.00
Summary
This study will investigate links between reproductive factors and body size of premenopausal women with their risk of major chronic conditions, such as cardiovascular disease, diabetes, and asthma. It builds on two decades of survey data from Australia’s flagship study of women’s health with a new biomedical assessment. Findings will guide the use of indicators of women’s reproductive health as a trigger for early and targeted approaches for chronic disease prevention.