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.
Novel Serological Tools To Aid Malaria Elimination In The Asia-Pacific
Funder
National Health and Medical Research Council
Funding Amount
$1,362,749.00
Summary
In 2014 Asia-Pacific leaders pledged a malaria free Asia-Pacific by 2030. We will contribute to this goal by developing novel antibody detection tests that can identify people with current and recent past infections. We will then evaluate the utility of these tests both in mass screening and treatment programs and for the rapid delineation of areas where transmission persists from those where it has been eliminated. This will address two major roadblocks to malaria elimination in our region.
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.
Monitoring Cortical Excitability Using A Probing Stimulus For Epileptic Seizure Anticipation
Funder
National Health and Medical Research Council
Funding Amount
$392,997.00
Summary
Millions of people with epilepsy suffer from seizures that cannot be controlled by medication. Life-threatening seizure may strike at any time, restricting patients from leaving their homes due the constant fear of a seizure. This research offers hope for people with epilepsy by developing a method of anticipating seizures. Successful outcomes will not only provide a warning of impending seizures, but also an opportunity for intervention, thereby preventing seizures.
Understanding The Roles Of Dendritic Domains In Neuronal Function
Funder
National Health and Medical Research Council
Funding Amount
$491,509.00
Summary
We aim to find cellular basis to cognitive function and dysfunction by understanding the input/output characterstics of individual neurons. Since neurons are fundamental computational units in the brain, we aim to understand how synaptic inputs to different dendritic regions are processed prompting the neuron to fire an output. We also aim to seek distinct roles of certain dendritic branches in gating sensory inputs onto the neuron.
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.
Molecular Networks And Genomics Of Host Response In Typhoid Fever
Funder
National Health and Medical Research Council
Funding Amount
$487,814.00
Summary
Typhoid fever affects 25 million people annually and is caused by systemic infection with Salmonella Typhi or Paratyphi. With this proposal, we will characterise how different individuals respond differently to typhoid, what ramifications this has for systemic Salmonella infection in humans, and how typhoid can be clinically identified early on, thus giving the patient the best possible chance to avoid complications, injury and potential death.
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