THE EFFECT OF STRESS AND ENVIRONMENTAL ENRICHMENT ON DISEASE PROGRESSION IN MESIAL TEMPORAL LOBE EPILEPSY
Funder
National Health and Medical Research Council
Funding Amount
$578,201.00
Summary
Mesial temporal lobe epilepsy, the most common form of drug-resistant epilepsy in adults, is a progressive neurodegenerative condition for which there is currently no effective disease modifying treatment. This proposal will explore whether co-morbid stress accelerates disease progression in MTLE, and whether targeting stress pathways by medical and environmental manipulations can mitigate against this.
Motivational drive and reward are survival processes that underpin the maintenance of homeostasis. In humans, dysregulation of these brain circuits manifests in disorders such as depression and addictions. Our projects is focused on a key subgroup of neurons in the hypothalamus that modulates reward and motivation. We aim to understand how potent reward experience (e.g. drugs) or stress modifies these circuits and to identify potential entry points for therapeutic interventions.
A Novel Role For Proteolysis In Promoting Inner Ear Cell Injury And Hearing Loss
Funder
National Health and Medical Research Council
Funding Amount
$972,818.00
Summary
Nearly 40% of hearing loss is attributable to traumatic noise exposure. This project will test a new idea that cells in the inner ear are damaged and die via noise-induced proteolysis, and investigate whether a similar mechanism operates during age-related hearing loss. It will open new avenues for therapies to preserve hearing where trauma is unavoidable, or has occurred through accident or incident.
The choice of anaesthetic agent used during cancer surgery could reduce the chances that the tumour will relapse, according to our preliminary findings. Surgery releases stress hormones and inflammatory molecules, which we have shown to increase the chance of cancer recurrence. The proposed study explores how the choice of anaesthetic agent used in cancer surgery can block the adverse effects of surgical stress, and stop cancer coming back.
Stress-induced Genomic Instability As A Driver Of Adaptive Responses In Human Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$690,426.00
Summary
Growing experimental evidence suggests human cancer cells use evolutionary conserved programs to regulate their mutation rates in response to pharmacological agents, accelerating adaptation and the emergence of resistance. The purpose of our study is to identify the common molecular pathways and genetic mechanisms driving the regulation of mutation rates. Targeting of these pathways using a new generation of “anti-evolution” drugs is an attractive possibility for novel therapeutic approaches.
Validating Novel Biomarkers Relevant To Major Depression
Funder
National Health and Medical Research Council
Funding Amount
$515,550.00
Summary
Depression prevention and treatment are public health priorities; therefore, it is critical to improve and personalise treatments, which can only be achieved by advancing knowledge of its underlying biology. This research project will contribute to validating potentially relevant genes for MDD risk or antidepressant response and to provide the scientific foundation for future strategies to test their products as MDD biomarkers in the clinical setting.
Skeletal Disease In A Dish: Using Novel In Vitro Disease Models Produced From Patient Induced Pluripotent Stem Cells To Reveal Pathogenic Mechanisms And Explore Treatments For Genetic Skeletal Disorders
Funder
National Health and Medical Research Council
Funding Amount
$808,551.00
Summary
Inherited skeletal disorders are a significant disease burden. Many gene mutations have been defined but we only have limited understanding about how they cause the disease. We will use patient skin cells and a new in vitro cell reprogramming technology to induce them to form cartilage and bone cells to produce mutation-specific “disease in a dish” models. These models will allow us to answer questions about how specific mutations cause disease and test novel drug therapies
Altered Nuclear Trafficking And Nuclear Body Dynamics As Drivers Of Ataxin-1 Toxicity
Funder
National Health and Medical Research Council
Funding Amount
$755,190.00
Summary
Ataxias are a large group of neurodegenerative disorders in which balance, motor skills and memory are progressively lost. While mutations in specific proteins do cause certain hereditary ataxias, the mechanisms of their detrimental actions is unclear. Our studies probe the toxic mechanisms of the ataxin-1 protein, focusing on its partners and stress-initiated formation of a toxic hydrogel state. The outcomes will define impacts on cellular protein movement in neurodegeneration more broadly.
Host Metabolism And Responses Contributing To Flavivirus Replication And Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$592,772.00
Summary
We aim to determine how viruses affect the cells they infect, In particular how they can alter the metabolism and balance of lipids in cells and how this impacts the bodies capability to respond immunologically. We believe that by understanding these basic principles we can target ares fr antiviral therapeutic potential.
Biological, Phenotypic And Public Health Costs Of Risk And Protective Pathways To Non-communicable Disease In Children And Adults: The National Longitudinal Study Of Australian Children
Funder
National Health and Medical Research Council
Funding Amount
$1,521,590.00
Summary
Although a late event for most Australians, chronic diseases present a crippling burden for Australia. This project explores their early roots, before overt disease emerges, in 3500 parents and their children in the Longitudinal Study of Australian Children. We will measure how accumulated stress and buffering characteristics play out in the biology of cell ageing and inflammation, in developing heart, lung, kidney and bone health, and in quality of life and health costs to the population.