Developing Exon Replacement Gene Therapy To Cure Rett Syndrome: An Innovative Model For Neurodevelopmental Disorders
Funder
National Health and Medical Research Council
Funding Amount
$475,105.00
Summary
There is no cure for neurodevelopmental disorders such as Rett syndrome which is caused by mutations in the MECP2 gene. Gene therapy is ineffective due to the 'Goldilocks' effect where too little, as well as too much expression of MECP2 causes disease. Here a gene editing therapy will be tested in patient cells and mouse model that will maintain the normal cellular expression of MECP2 by cutting out the mutated regions of the gene (exons) and replacing them with repaired copies.
Vascular Changes Are A Key Contributor To And Novel Drug Target For Interferon-alpha Induced Neurological Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,245,401.00
Summary
Type I interferons (IFN-Is) contribute to wide range of neurological diseases including ageing and neurodegeneration. At its extreme IFN-I-mediated neurodegeneration is known as 'interferonopathy'. The mechanisms of how IFN-Is drive disease are unclear, making causal treatment difficult. We have recently uncovered ground-breaking evidence that abnormal blood vessels are a key contributor to the disease. Here, we will investigate novel treatment targets for patients with interferonopathies.
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.