Investigating The Clinical And Research Applications Of Whole-genome Sequencing In Parkinson Disease And Other Movement Disorders
Funder
National Health and Medical Research Council
Funding Amount
$266,623.00
Summary
There are many ‘movement disorders’ including Parkinson disease, dystonia, and hereditary spastic paraplegia. These disorders can be caused by mutations (errors in the genetic code) in different genes. The discovery of these genes has improved our understanding of the underlying disease mechanisms. We will use ‘whole genome sequencing’ to read a person’s entire genetic material in a single experiment, allowing us to identify a genetic diagnosis and to discover entirely new disease-causing genes.
Translating Epilepsy Research Into Clinical Practice
Funder
National Health and Medical Research Council
Funding Amount
$188,226.00
Summary
We aim to turn laboratory science into real improvements in the health of people with epilepsy. Firstly, a rise in the acidity of the blood from breathing less and a rise in carbon dioxide, may contribute to seizures finishing. We aim to develop a safe, rapid, non-sedating way to treat seizures using a small amount of carbon dioxide in oxygen. Secondly, inherited problems with transporting sugar from the blood to the brain are increasingly recognised as a cause of epilepsy. We will develop a nat ....We aim to turn laboratory science into real improvements in the health of people with epilepsy. Firstly, a rise in the acidity of the blood from breathing less and a rise in carbon dioxide, may contribute to seizures finishing. We aim to develop a safe, rapid, non-sedating way to treat seizures using a small amount of carbon dioxide in oxygen. Secondly, inherited problems with transporting sugar from the blood to the brain are increasingly recognised as a cause of epilepsy. We will develop a nation-wide program to identify and treat theseRead moreRead less
Human Epilepsy: Understanding Biology To Improve Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$16,657,948.00
Summary
Our team of neurologists, molecular geneticists, physiologists and brain imaging specialists and leads the world in the discovery of the genetic causes of epilepsy. Through this work we will identify genes underlying epilepsy and study how genetic variations result in the development of seizures. Advanced brain imaging will be used to understand the effects of genetic variation on brain structure and function. This study may lead to new diagnostic methods and treatments for epilepsy.
The Role Of Netrin-DCC In The Development Of The Corpus Callosum
Funder
National Health and Medical Research Council
Funding Amount
$512,065.00
Summary
During embryonic development neurons send out axons that connect to other target neurons within the brain. The proper connectivity of these axons is vital to brain function. The largest axon tract in the brain is called the corpus callosum and connects neurons in the left and right cerebral hemispheres. When the corpus callosum does not form, significant cognitive, motor and sensory deficits occur in patients. This condition, known as agenesis of the corpus callosum (ACC), is associated with ove ....During embryonic development neurons send out axons that connect to other target neurons within the brain. The proper connectivity of these axons is vital to brain function. The largest axon tract in the brain is called the corpus callosum and connects neurons in the left and right cerebral hemispheres. When the corpus callosum does not form, significant cognitive, motor and sensory deficits occur in patients. This condition, known as agenesis of the corpus callosum (ACC), is associated with over 50 different human congenital syndromes. Thus understanding how the genes and molecules involved in the formation of the corpus callosum function in normal development can provide the basis for our understanding of what goes wrong in ACC. In this proposal we will investigate the role of the axon guidance molecule Netrin1, and its receptor DCC, in development of the corpus callosum in both a mouse model and in humans with malformations of the corpus callosum. Although Netrin1-DCC signalling has traditionally been associated with mechanisms of axon guidance, we hypothesize that these molecules may play a different role, specifically in cellular adhesion and ultimately in the fusion of the two cerebral hemispheres, in a manner that allows the corpus callosum to form. A second role for Netrin1-DCC signalling may be in the guidance of these axons once the midline has fused correctly and we investigate this in Aim 2 of the proposal. Finally, we are collaborating with a paediatric neurologist at UCSF, who has identified several mutations in the DCC gene in patients with ACC. In Aim 3 we test whether these mutations disrupt the function of DCC in callosal axon pathfinding. Understanding how these genes function during development of the brain and how their function may be altered in ACC is crucial to providing a proper diagnosis and prognosis for these patients. Ultimately, understanding more about how these genes function could also lead to prevention of these disorders.Read moreRead less
How are memories stored in the brain? We know much about the brain regions involved in memory storage but we know little or nothing about how individual memories are represented and stored within those brain areas. The purpose of this project is to label and manipulate the specific subsets of brain cells that store individual memories. We will label memory-bearing cells in multiple brain regions and then ask how the connections between those cells encode learned information in the brain.
Multiple Sclerosis (MS) is an autoimmune disease often diagnosed in early adulthood. Outcomes very enormously, from mild to disabling. This fellowship supports research to improve outcome prediction using genetics and to examine different strategies to optimise treatment outcomes and safety. The main data source is MSBase, which tracks over 31000 people with MS globally and is based in the University of Melbourne's brain Centre at the Royal Melbourne Hospital.
Blood-brain Barrier And White Matter Damage In The Immature Rat Brain Following Systemic Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$353,173.00
Summary
Clinical obstetric and paediatric studies have identified an association between intrauterine infection occurring around two thirds of the way through pregnancy, premature birth and a specific form of damage to the brain of the newborn. This damage mainly affects white matter tracts. These tracts are aggregations of nerve fibres that make the connections between different parts of the brain and may result in cerebral palsy or other neurological disorders. The association between maternal infecti ....Clinical obstetric and paediatric studies have identified an association between intrauterine infection occurring around two thirds of the way through pregnancy, premature birth and a specific form of damage to the brain of the newborn. This damage mainly affects white matter tracts. These tracts are aggregations of nerve fibres that make the connections between different parts of the brain and may result in cerebral palsy or other neurological disorders. The association between maternal infection and brain damage, one form of which is cerebral palsy, is well established from clinical epidemiological studies, but the biological mechanism of this link is unknown. The CIs' group has recently shown that the condition can be reproduced in neonatal rats at a stage of brain development in the rat that is equivalent to the critical time in human brain development when infection may be associated with brain damage. The CIs' group has shown that an induced inflammatory state similar to a bacterial infection, results in damage to blood vessels in the white matter and is associated with changes in white matter, as occurs in affected babies. The purpose of this study is to understand the nature of the damage to white matter blood vessels and the mechanisms by which materials in blood, which in the normal brain do not pass from the blood to the brain across the blood-brain barrier, are able to do so via the inflammation damaged blood vessels. The study also aims to show whether it is components of the blood entering the brain via the damaged blood vessels that are responsible for the damage to white matter in the immature brain. The outcome should lead to development of ways to improve clinical care of women who acquire infections during pregnancy.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120101311
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Role of intrinsic versus extrinsic cues in cell type determination during development and regeneration. During development all of the different cell types are generated by the action of genes and also signals from the embryo that read out which cell types are present or missing. This project studies how much environmental signals affect cell type generation developmentally and if they can be used to regenerate only the types missing in different diseases.
Discovering Deep Sleep Genes And Determining Their Roles For Preserving Cognitive Functions
Funder
National Health and Medical Research Council
Funding Amount
$484,901.00
Summary
Our mental well-being is largely tied to our sleep quality, and most cognitive disorders are also associated with poor sleep processes. Yet, we still do not know how sleep quality safeguards cognitive function. We will uncover genes that play a restorative role during deep sleep, and determine how genetic control of these deep sleep genes modulates selective attention in an animal model. Our results will suggest novel therapies for treating sleep disorders and associated diseases of the brain.