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.
Nanoengineered Bioelectronic Systems For All-Optical Control Of Neuron Growth And Stimulation
Funder
National Health and Medical Research Council
Funding Amount
$757,452.00
Summary
Nerve cells are the primary signal carriers of the human body. When they cease to function normally, our bodies ability to function and sense the physical world is influenced catastrophically. We will develop a new bioelectronic system made by printing clever inks that can artificially stimulate nerve cells without the typical requirements for invasive metal electrodes or external power. These new scientific advances will revolutionize nerve cell repair and treatment of neurological disorders.
Silencing Pulmonary Nociceptors To Treat Severe Respiratory Viral Infections
Funder
National Health and Medical Research Council
Funding Amount
$534,173.00
Summary
The lungs receive a rich supply of nerve fibres, many of which play an important role in helping defend against pathogens, including viruses. When viral infections become severe, too much inflammation occurs in the lungs and this creates a serious and difficult to treat clinical problem. Hundreds of thousands of people each year die from the complications of severe lung infections. We are investigating a potential new therapy that targets the lung nerves and relieves excessive inflammation.
Innate Threat Detection Circuits In The Superior Colliculus Co-ordinate Respiratory And Cardiovascular Responses To Visual Stimuli
Funder
National Health and Medical Research Council
Funding Amount
$517,958.00
Summary
Our surroundings affect our bodies: light pollution, traffic, and aircraft noise all significantly affect cardiovascular health. This project will investigate interactions between brain systems that subconsciously scan our surroundings for interesting or threatening features, and those that co-ordinate the cardiovascular and respiratory systems. We will generate new knowledge that describes how the brain detects danger and translates this into signals that contribute to cardiovascular risk.
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.
Intergenerational Impacts Of Paternal Immune Activation On Brain Function And Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$997,690.00
Summary
We recently discovered that infection of male mice with a parasite (Toxoplasma gondii) before conception can change the epigenetic information in the sperm and alter behaviour of the offspring. This is the first evidence that pathogenic infection in males can affect the next generation. We will investigate how infection with other major pathogens, including bacteria and the virus causing COVID-19, may affect sperm epigenetics and offspring health, including their brain function and dysfunction.
Predicting Clozapine Treatment Response In Psychotic Illness
Funder
National Health and Medical Research Council
Funding Amount
$721,526.00
Summary
Not everyone with a psychotic illness gets better when treated with standard antipsychotic medication. We aim to better understand why some people need a different medicine (clozapine), and to develop methods that will let us identify those people early and monitor how effective the treatment is.
Establishing The Neural Basis Of Auditory-verbal Hallucinations In Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$563,020.00
Summary
Auditory-verbal hallucinations (AVH) - or hearing voices when no one is talking - are characteristic and debilitating symptoms of schizophrenia. AVH have been hypothesized to reflect inner speech being misperceived as external speech. Our research team has developed an objective brain marker of inner speech. We will use this marker to determine whether AVH are caused by abnormal inner speech in people with schizophrenia. Findings will inform treatments for this incapacitating disorder.
Narcolepsy With Cataplexy: A Brain Orexin Replacement Strategy
Funder
National Health and Medical Research Council
Funding Amount
$810,784.00
Summary
Narcolepsy with cataplexy is a debilitating, life-long sleep-wake disorder, caused by the irreversible loss of the brain peptide 'orexin'. There is no satisfactory and safe treatment. We aim to develop an orexin analogue, delivered directly to the brain of sheep (relevant in size and translatable to patients) by a programmable pump to timely activate the orexin 'wake-up' switch. This innovative precision medicine project will significantly improve the quality of life of narcolepsy patients.
Creating A Phenotypic Catalogue Of Synaptic Vesicle Cycling Disorders
Funder
National Health and Medical Research Council
Funding Amount
$876,975.00
Summary
Developmental disorders affect 2-5% of children. In order to understand how these mutations will likely affect neurological function in these individuals, and to develop a tailored care and treatment program, we must first understand how these mutations affect neuronal communication. This research program will identify the underlying cause of neurological dysfunction in a subset of these disorders (synaptic vesicle cycle disorders), affecting 1200-3000 children in Australia alone.