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The Role Of Non-classical MHC Class I Molecules In Adaptive Immunity
Funder
National Health and Medical Research Council
Funding Amount
$443,834.00
Summary
Specialised proteins called MHC class Ia molecules (MHC-Ia) stimulate killer T cells to lyse virus infected cells. In contrast, the function of the closely related MHC-Ib is uncertain. Recent findings have demonstrated that MHC-Ib can also be recognised by T cells and this interaction is important in the control of viral infections. However, despite the similarity to MHC-Ia, it is unclear how this interaction occurs. This project aims to investigate how killer T cells recognise MHC-Ib molecules.
Dysfunction In Anterior Cingulate Brain Networks: Implementations For Psychiatric And Substance Use Disorders
Funder
National Health and Medical Research Council
Funding Amount
$380,558.00
Summary
Psychiatric and substance use disorders are associated with significant morbidity and mortality. Recent evidence points to discrete brain networks as being critically involved in the neurobiology of these disorders. Using novel brain imaging techniques, this research will increase our knowledge of how these brain networks are involved in these disorders. This will represent an important step towards elucidating their biological underpinnings and improving outcomes for affected patients.
This research proposal will identify changes in liver-secreted proteins during the development of fatty liver, and in the transition from fatty liver to the more advanced form of liver disease, non-alcoholic steatohepatitis (NASH). Understanding the differences in protein secretion between NASH patients and patients with normal/fatty liver will provide the opportunity to identify disease biomarkers that could be determined from a blood sample. This will provide a major shift in clinical care.
The Role Of The Zinc Finger Transcriptional Repressor Znf238 During Nerve Cell Maturation
Funder
National Health and Medical Research Council
Funding Amount
$394,264.00
Summary
Proper foetal brain assembly is critical for brain function, but the underlying genetic mechanisms remain poorly defined. In this study, I will investigate a family of proteins that “turn on” neural gene expression in combination with another protein that “turns off” their expression during nerve cell development. Understanding this novel on/off mechanism for controlling gene expression in newborn nerve cells will further our understanding of how the brain is assembled.
Discovering And Targeting Genes Regulating Skeletal Muscle Function, Metabolism, And Adaptations To Exercise Interventions
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Muscle wasting and decreased in mitochondrial function due to ageing or lack of physical activity are associated with reduced quality of life. The overarching aim is to develop a unique research program focusing on targeting specific genes, and to discover novel genes regulating muscle wasting and mitochondrial (dis)function. I anticipate this approach to assist in the development of targeted and personalised prevention and therapy for diseases associated with muscle (dis)function.
Wnt Signaling In Dopaminergic Neuronal Connectivity
Funder
National Health and Medical Research Council
Funding Amount
$387,489.00
Summary
During development, the brain establishes intricate and precise connections. In several brain pathways, little is known about the processes regulating this connectivity. Furthermore, it is likely that the same processes will be required to repair the injured- diseased brain. This project builds on our preliminary data, that Wnt proteins are important regulators of developing dopamine pathways, and has implications for dopamine disorders including Parkinson’s disease and addiction.
Enabling Personalised Risk Assessment For Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Bowel cancer screening will be most effective in disease prevention if it is applied proportionately to individual person's risk. Risk-based screening requires a risk calculator to assess personal risk. By utilising existing large, international datasets, I will identify the risk factors specific for different bowel cancer types and incorporate them to upgrade the prediction model that I have developed. This will achieve more accurate risk prediction to enable personalised risk-based screening.
Functional Genomics Of Malaria Liver Infection And Transmission
Funder
National Health and Medical Research Council
Funding Amount
$470,144.00
Summary
Chemotherapy is the front line defense against malaria but resistance is emerging. The WHO has advised that new drugs should target parasite stages that perpetuate the transmission of malaria to break the cycle of infection. We have identified proteins that are essential for the two transmissive stages of the most deadly parasite to infect their hosts. We will determine the precise function of these proteins and the mechanisms they govern. This may guide the development of new interventions.
Development Of Cancer Immunotherapy Using Gene-engineered T Cells In A Self-antigen Mouse Model
Funder
National Health and Medical Research Council
Funding Amount
$428,602.00
Summary
Killer T lymphocytes can penetrate tumours and their transfer into cancer patients has demonstrated some encouraging results, but this form of therapy and other approaches including vaccination remain ineffective in most cancer patients. In this project, we propose to improve the tumour trafficking and anti-tumour activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells.