Problems in learning, memory and other complex mental processes are common to many brain disorders. This project will study the impact of mutations on a family of genes reported in autism and schizophrenia, on complex cognitive behaviours using novel behavioural technologies. This will not only shed fundamental insights into the specific mental processes regulated by these genes and their role in disease, but importantly provide novel targets for the development of therapies.
Slowing Progression Of Alzheimer’s Disease By Modulating The Kynurenine Pathway
Funder
National Health and Medical Research Council
Funding Amount
$578,460.00
Summary
Chronic inflammation in the brain in known to be a factor in the progression of Alzheimer's disease. We are exploring if blocking a particular enzyme in a biochemical pathway involved in inflammation, can improve symptoms, or slow progression, of the disease in animal models of AD. If results are as expected, our proposal has the potential to generate a new a therapy for AD.
The majority of stroke results from focal brain infarction, followed by substantial secondary excitotoxic damage in the surrounding areas. Tau has been shown to contribute to excitotoxicity and neurodegeneration in mouse models of Alzheimer’s disease (AD). Preliminary data show that tau reduction also protects against excitotoxic damage after experimental stroke. We aim to dissect the molecular mechanisms of stroke using a tau-deficient mouse model.
Assessing The Efficacy Of Safe And Simple Neuroprotective Treatments For Chronic Degenerative Conditions Of The Central Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$311,860.00
Summary
Current treatments for age-related diseases of the central nervous system (CNS) are limited. We have shown in animal models of acute CNS degenerations that treatment with saffron or low energy infrared light is strongly protective. This project will determine if these treatments prevent CNS damage and dysfunction in animal models of chronic degenerations and add to knowledge of how these treatments work. This research should lay the foundation for testing these novel treatments in humans.
Targeting Autism With Macrocephaly Using Mechanism Based Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$831,652.00
Summary
Autism affects a large number of children in our community and currently there is a lack of any medication to treat its core pathology. In this grant we will study the underlying biochemical changes in the brain that result in autism through the development of a new mouse model of the disorder. This mouse model will then be used test drugs to identify therapeutic targets for the treatment of autism.
NOVEL MECHANISMS UNDERLYING THE SPREADING OF TAU PATHOLOGY IN ALZHEIMER’S DISEASE AND OTHER TAUOPATHIES
Funder
National Health and Medical Research Council
Funding Amount
$640,106.00
Summary
Alzheimer’s disease and related dementias affect 230,000 people in Australia, with numbers expected to grow to three times that by 2050. The direct costs for health and residential care alone already exceed $6.6 billion per annum. The underlying pathomechanisms and the processes that drive the progression of neurodegeneration in these devastating disorders remain largely unknown. Here, we will identify novel therapeutic targets and assist in developing therapies for yet incurable diseases.
Long-term Outcomes After Paediatric Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Traumatic brain injuries during early childhood often result in long-lasting issues including social behaviour problems and post-traumatic epilepsy. Using a unique model of brain injury in young mice, my research aims to identify the biology underlying the changes that cause these issues, and evaluate novel approaches to improve long-term outcomes after brain injury.
The Missing Link: MGluR5 As A Therapeutic Target For Cognitive Decline In Dementia
Funder
National Health and Medical Research Council
Funding Amount
$563,622.00
Summary
Cognitive decline is a core feature of Alzheimer’s Disease (AD), yet there is no cure or treatment. Recent evidence suggests that a protein called mGluR5 could cause brain cells to lose function, leading to memory loss. This project will investigate whether disrupting mGluR5 function can improve cognition in mice with genetic AD. Memory will be assessed in mice using innovative touchscreen tests that closely mimic the tests used in humans.
The Role Of The Gtf2i Gene Family In Behaviour And Williams Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$629,396.00
Summary
Williams Syndrome (WS) is a complex neurodevelopmental disorder in humans caused by a deletion of 21 genes on chromosome 7. This results in a reduced IQ and marked visuospatial deficiencies. However, unlike other forms of mental retardation, some important cognitive abilities are completely normal. WS patients show normal development of linguistic abilities and anecdotal evidence suggests they possess an above average musical ability. In addition, these individuals also possess a characteristic ....Williams Syndrome (WS) is a complex neurodevelopmental disorder in humans caused by a deletion of 21 genes on chromosome 7. This results in a reduced IQ and marked visuospatial deficiencies. However, unlike other forms of mental retardation, some important cognitive abilities are completely normal. WS patients show normal development of linguistic abilities and anecdotal evidence suggests they possess an above average musical ability. In addition, these individuals also possess a characteristic overfriendly, gregarious personality with little inhibition towards strangers. Such a characteristic cognitive and behavioral profile in a genetic disorder has provided convincing evidence that genes play a role in specifying cognitive abilities and behavior. This interesting syndrome gives us an insight into the perplexing debate of Nature vs Nurture. It also provides a unique and invaluable opportunity to dissect the role of certain genes in complex neurodevelopmental pathways that result in cognition and behavior. Recently, patients with smaller (atypical) deletions of genes in the WS region have been described. These patients do not display the full 'classical' range of WS characteristics. The identification of which genes are deleted in these patients suggests that two genes in particular, GTF2IRD1 and GTF2I, are involved in visuospatial abilities, sociability and specific anxieties and phobias. Our laboratory was the first to identify proteins encoded by GTF2IRD1, known as MusTRDs, that act for the most part to suppress gene expression. Furthermore, our laboratory has been studying a mouse model in which the Gtf2ird1 gene has been deleted, similar to the situation in WS, and have found that the mice are more 'social' and exploratory. In this project, we want to determine if other behavioural features of WS are contributed to by this gene and-or its related gene, Gtf2i, and to characterize the role that these genes play in neuronal cell function.Read moreRead less