Understanding The Mechanisms Of PTEN Transfer Into Glial Cells Using Exosomes
Funder
National Health and Medical Research Council
Funding Amount
$567,253.00
Summary
This application will develop a new way of treating brain cancer which currently affects 1500 adults in Australia per year with no lasting cures. The average patient with a malignant brain tumour do not survive for more than 12 months. We have discovered a method of restoring a cancer suppressor substance that is lost from brain tumours. If successful, this treatment has the potential to limit or reverse the progression of brain tumours.
Cerebral Palsy (CP) is a devastating, common developmental brain disorder once assumed to be due to lack of oxygen at birth. Using our unique Biobank with DNA and clinical data from families with a CP child, we are examining the genetic origins of CP and how genes and risk factors in pregnancy contribute. We will use computer modelling and testing in animals and brain cells, to understand causes of CP and devise predictive, preventative and therapeutic strategies.
Delayed Radial Glial Maturation Linked To NFI Deficiency As An Underlying Cause Of Cortical Defects In Humans And Mice
Funder
National Health and Medical Research Council
Funding Amount
$801,979.00
Summary
The timely generation of neurons and glia is important for brain development and consequently brain function throughout life. Nuclear factor I (NFI) genes are important for regulating the production of neurons and glia, and people with disrupted NFI genes have severe cognitive and motor deficits. Using human genetic data and mouse models, we will analyse how disrupting these genes affects brain development, and changes the overall structure and wiring of the cerebral cortex as well as behaviour.
Aberrant Ependymal Development And The Formation Of Hydrocephalus
Funder
National Health and Medical Research Council
Funding Amount
$660,005.00
Summary
Foetal hydrocephalus is a prevalent neurodevelopmental condition associated with severe intellectual impairment. Breakdown of the ependymal cell layer, which acts as a barrier between brain tissue and the ventricular space, is a major cause of hydrocephalus. Despite the importance of these cells, we have little understanding of the molecular mechanisms that regulate their production. This project will identify critical signalling pathways governing the establishment of the ependymal layer.
Investigating Early Life Exposure To Plastic Products In Australia And Subsequent Neurodevelopmental Effects
Funder
National Health and Medical Research Council
Funding Amount
$791,376.00
Summary
Child neurodevelopment disorders like autism are becoming more common. Recent work indicates almost all pregnant mothers in Australia harbour plastic chemicals – bisphenols and phthalates and foetus is also exposed. Human evidence is emerging that higher exposure to plastics during pregnancy may be associated with these disorders. Randomised controlled trials are not possible so high quality birth cohort studies, as proposed here, are required to investigate this issue comprehensively.
Pathogenesis And Therapeutic Modulation Of Aggressive Behaviour In A Mouse Model Of Autism Spectrum Disorder
Funder
National Health and Medical Research Council
Funding Amount
$583,015.00
Summary
This project focuses on understanding the causes of aggressive behaviour in mice that have a human gene mutation found in autism. Aggressive behaviour is common in autism patients and can have severe consequences on education and employment opportunities. These mice also show excess dampening of brain function (inhibition). This project will test if aggression in these mice is caused by altered inhibition.
Epigenetic And Neurobehavioural Changes In A New Mouse Model Of Foetal Alcohol Spectrum Disorders.
Funder
National Health and Medical Research Council
Funding Amount
$949,466.00
Summary
Prenatal alcohol exposure can result in foetal alcohol syndrome (FAS) which involves growth restriction, changes to skull morphology, central nervous system defects and intellectual disabilities. At present, diagnosis is difficult and under-reporting is suspected. We are using a mouse model to study the underlying causes of FAS, focussing on changes in brain structure and function. Hopefully we will identify markers that can be used for the early diagnosis of FAS in the future.
Investigating Secondary Effects Of BACE1 Inhibition, A Promising Therapy For Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$700,672.00
Summary
Synapses transfer information between neurons in the brain. In Alzheimer’s disease (AD), synapse loss results in dementia therefore it is imperative that any potential therapeutic drugs do not inadvertently cause further synapse loss. Drugs aimed at blocking production of toxic protein fragments in AD might have adverse secondary effects on synapse development and function. This research will determine whether this is the case and inform new therapeutic approaches aimed at minimizing side effect ....Synapses transfer information between neurons in the brain. In Alzheimer’s disease (AD), synapse loss results in dementia therefore it is imperative that any potential therapeutic drugs do not inadvertently cause further synapse loss. Drugs aimed at blocking production of toxic protein fragments in AD might have adverse secondary effects on synapse development and function. This research will determine whether this is the case and inform new therapeutic approaches aimed at minimizing side effects.Read moreRead less
Neogenin: A Molecular Determinant Of Neural Progenitor Polarity And Function
Funder
National Health and Medical Research Council
Funding Amount
$569,296.00
Summary
The neuroepithelium (NEP) contains the embryonic neural stem cells essential for the production of all neurons in the adult brain. Failure in NEP function leads to devastating neural tube defects and syndromes such as epilepsy, schizophrenia, and mental retardation. This project will identify the molecular mechanisms regulating NEP stem cell activity and the birth of new neurons in the embryonic neocortex.
Understanding The Embryonic Origins Of Cortical Malformations
Funder
National Health and Medical Research Council
Funding Amount
$815,228.00
Summary
Cortical malformation leads to mental retardation and epilepsy. Identification of the aberrant developmental processes contributing to these devastating syndromes is essential for accurate clinical assessment and development of novel therapeutics. Here we investigate a developmentally important receptor, Neogenin, which when mutated, leads to cortical malformations. Determining how Neogenin functions is expected to uncover new signaling pathways contributing to these malformations.