Understanding The Innate Immune Response To Viral Infection Of The Female Reproductive Tract And Placenta
Funder
National Health and Medical Research Council
Funding Amount
$784,273.00
Summary
Viral infection of the female reproductive tract (FRT) can have a significant impact on FRT health and may cause significant birth defects if the virus infects the placenta and developing fetus. In this application we will investigate the role of a novel molecule termed interferon epsilon and how it impacts viral infection of the FRT, the fetus and how the placenta responds to viral infection. This work will develop innovative antiviral strategies to combat viral infections of the FRT.
Exploiting Anti-capsid Humoral Immunity Induced In Infants Receiving Gene Therapy For Spinal Muscular Atrophy To Engineer The Next Generation Of Gene Transfer Vectors
Funder
National Health and Medical Research Council
Funding Amount
$1,105,993.00
Summary
After 25 years of incremental progress the possibility of treating genetic disease by gene therapy has become a therapeutic reality. This has been achieved by harnessing the gene transfer power of viruses made harmless by genetic engineering. A major limitation is that up to 50% of patients are currently excluded by pre-existing immunity to these powerful tools. Using 'evolution in a dish', we will engineer a new generation of these tools capable of bypassing pre-existing immunity by stealth.
THE IMMUNOLOGICAL LEGACY OF OBESITY ON VIRAL PATHOGENESIS
Funder
National Health and Medical Research Council
Funding Amount
$652,275.00
Summary
Obesity is a key risk factor for severe viral infections. Our preliminary data suggest that in mice this susceptibility is not reduced by weight loss. In this grant we will investigate a) the mechanisms driving the legacy effect of obesity on antiviral immunity b) whether or not we can reverse this legacy effect by treatment with the drug MCC950 and c) the antiviral response of overweight children and adults who have and haven't recently lost weight.
Developing New Immunotherapeutics Through Studying Immune Effectors In Situ
Funder
National Health and Medical Research Council
Funding Amount
$1,369,054.00
Summary
The immune system deploys pore forming proteins to clear viral and bacterial infections and to eliminate cancerous cells. The unwanted activities of these molecules, however, results in chronic disease and in transplant rejection. We aim to understand how pore forming immune weapons interact with our own cells, with the goal of using this information to develop new approaches to treat immune driven disease and to improve the success of transplantation therapy.
Hepatitis B is a leading cause of cirrhosis and liver cancer. Treatments for hepatitis B control the virus, but do not cure it, so people stay on treatment for many years. We have identified an exciting new treatment approach by targeting a gene that controls liver metabolism, called TM6SF2. We will target this gene to develop a cure for hepatitis B.
Targeting Neurovascular Communication As A Novel Way Of Reducing Vision Loss In Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$986,663.00
Summary
Diabetes is a leading cause of blindness. Here, we evaluate whether diabetes causes changes in the way neurons signal to blood vessels, and whether blocking some of the signals from neurons reduces blood vessel abormalities. Overall, this information is critical to our understanding of the early changes that occur during diabetes and whether novel treatments used early in diabetes can prevent long term changes and vision loss.
Dissecting Brain Network Ageing Using Whole Brain Imaging
Funder
National Health and Medical Research Council
Funding Amount
$692,964.00
Summary
In this proposal, we will make the first attempt to map the whole brain activity change during ageing using a series of state-of-the-art techniques. We will also identify genetic and pharmacological interventions that improve brain network function during ageing. Outcomes from this research will provide an unprecedented understanding of functional ageing within the brain and identify therapeutic interventions to prevent this process.
Organisation Of The Genome During The Development Of Antibody-secreting Cells
Funder
National Health and Medical Research Council
Funding Amount
$886,155.00
Summary
Each cell of our body contains over two metres of DNA that must be correctly packaged in order for our cells to function. We are using cutting-edge molecular biology techniques to study how this DNA circuitry is established in the white blood cells of our immune system that produce antibodies. Our novel approaches will reveal unique strategies to modulate immune responses to our benefit.
A Novel Interaction Between The Immune And Vascular Systems In Early-onset Preeclampsia; An Opportunity For New Treatments?
Funder
National Health and Medical Research Council
Funding Amount
$921,623.00
Summary
Preeclampsia is a pregnancy complication that leads to poor birth outcomes and elevated lifelong cardiovascular disease risk in 4 million women each year. It has no cure and treatments are limited because the causal mechanisms are not understood. We have identified a specialised immune cell in the mother's blood that assists blood vessels to function properly in pregnancy. We will assess whether interventions to enhance these cells can improve poor blood vessel function and pregnancy outcomes.
About one in eight known genetic disorders involve DNA alteration that activates a cellular quality control mechanism that disables the affected gene. This mechanism is more efficient in some individuals than others. It can influence disease outcomes and severity. We will engineer and apply tools and models to measure and manipulate this crucial cellular mechanism. This will allow us to predict disease severity as well as to intervene where a manipulation of this mechanism will be beneficial.