Investigating The Role Of Mitochondrial Tom40 In Regulated Cell Death And Neurodegeneration.
Funder
National Health and Medical Research Council
Funding Amount
$972,660.00
Summary
Mitochondria are internal compartments of cells, separated by bounding membranes. They are crucial to the life and death of cells, and to quality of human life and ageing. Diseases of the nervous system can be caused when mitochondria do not function properly. Our aim is to discover why a protein complex called TOM embedded in the bounding membrane is linked to dementia in some people. This will also lead to a better general understanding of the connection between mitochondria and human health.
Are Oligodendrocytes The Missing Link In Amyotrophic Lateral Sclerosis Pathogenesis?
Funder
National Health and Medical Research Council
Funding Amount
$1,054,405.00
Summary
Amyotrophic Lateral Sclerosis (ALS) is a debilitating and progressive neurodegenerative disease. Recent research suggests important cells of the central nervous system called glia play a role in disease onset and progression. We are interested in a type of glia called oligodendrocytes; they are crucial for supporting the survival of the cells that die in ALS. Only through understanding the underlying biology of ALS can we aim to identify effective therapies that will benefit patients.
Bivalent Analgesics: Rational Design Of Selective Ion Channel Inhibitors With Optimised Mechanism Of Action
Funder
National Health and Medical Research Council
Funding Amount
$904,890.00
Summary
The so-called 'opioid crisis' leading to the death of millions of people worldwide has highlighted the urgent need for development of novel safe and efficacious pain killers without addictive potential. This proposal aims to rationally design novel analgesic compounds by linking different classes of ion channel modulators with desirable properties.
Investigating The Consequences Of Dysregulated Lipogenesis In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$600,647.00
Summary
Reprogramming of cellular metabolism is a hallmark of cancer. As such, there has been growing interest in developing strategies to exploit metabolism for therapeutic gain. Our ability to do this is dependent on a thorough understanding of the mechanisms by which dysregulation of cellular metabolism contributes to tumour progression. In this project, we seek to the investigate the fundamental mechanisms by which aberrant activation of lipid metabolism contributes to the tumourigenic process.
Oleoyl-ACP-hydrolase As An Early Predictive Biomarker For Severe And Fatal Influenza
Funder
National Health and Medical Research Council
Funding Amount
$866,807.00
Summary
Millions are hospitalized with severe influenza disease and ~500K die annually but the underlying mechanisms that drive disease are still not fully understood. We have identified a key role for an enzyme involved in fatty acid metabolism, which is profoundly elevated in patients who succumb to influenza and is thus a predictor for fatal outcomes. This research aims to investigate how this enzyme affects infection and impairs immune responses to drive severe respiratory viral disease.
The Interactive Effects Of Dietary Saturated Fat And Apolipoprotein-E Genotype On Peripheral Metabolism Of Lipoprotein-amyloid And Neurovascular Integrity.
Funder
National Health and Medical Research Council
Funding Amount
$637,536.00
Summary
This project is based on a remarkable discovery which suggests that in some individuals, Alzheimer's disease may be a consequence of corruption of microscopic blood vessels that supply brain, damaged as a consequence of exaggerated exposure in blood to a protein produced principally in liver. The project will explore this pathway further in subjects at heightened risk of Alzheimer's disease and in humanised animal models. The findings may provide new opportunities for prevention and treatment.
Characterisation And Targeting T Cellular Metabolism To Improve Control Of Chronic Viral Infections
Funder
National Health and Medical Research Council
Funding Amount
$791,427.00
Summary
CD8+ T cells are the frontline warriors of our immune system that can eliminate infected or cancerous cells. However, diseases caused by overwhelming viral infections are associated with widespread impairments in immunity and cellular metabolism. Here, we propose to examine molecular pathways involved in cellular metabolism that could be utilized to improve therapies against viral infection and cancer.
Biosensor Based Clinical-decision Support For Patients With Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$691,933.00
Summary
Heart Failure (HF) is a progressive disease and a major global public health concern. HF accounts for a substantial number of hospitalisations, major healthcare resource utilisation and costs. We aim to engineer biosensor platform to stratify the risk in HF patients will revolutionise current management of HF by providing the cardiologist information to risk stratify patients based on protein signature. This will lead to a substantial paradigm shift in clinical practice.
Molecular Characterisation Of The DBHS Proteins In Telomerase Assembly
Funder
National Health and Medical Research Council
Funding Amount
$686,246.00
Summary
Telomerase is an enzyme that is active in over 90% of cancers. Telomerase activity allows cancer cells to divide an indefinite number of times. We have identified a novel role for the DBHS protein family in regulating telomerase activity. We aim to investigate the mechanisms by which these proteins function to assemble and transport telomerase to its site of action in the cell. We then aim to develop chemical inhibitors of these proteins, and test their utility in preventing cancer cell growth.
Validating CaMKK2 As A Rational Treatment Target For Bipolar Disorder
Funder
National Health and Medical Research Council
Funding Amount
$688,175.00
Summary
Bipolar disorder is a disabling, chronic mental illness that profoundly impairs the ability of affected individuals to function in daily life. Existing treatments for bipolar disorder are inadequate and lack the necessary efficacy and tolerability required for long-term therapy. This project will validate the enzyme, CaMKK2, as a rational treatment target for bipolar disorder, which will guide the development of more effective and safer drugs to improve patient outcomes.