An Investigation Into The Molecular Basis Of MAIT Cell Recognition Of Vitamin B Based Metabolites
Funder
National Health and Medical Research Council
Funding Amount
$883,762.00
Summary
Mucosal associated invariant T cells (MAIT cells) are an abundant T-cell population in humans, that is found mostly in the gastrointestinal mucosa. We have recently shown that MAIT cells can be activated by metabolites of vitamin B. This proposal will investigate how the MAIT cells "see" vitamin B metabolites. This research will pave the way for novel therapeutics that can modulate MAIT cell activity.
KYNURENINE PATHWAY METABOLOMIC PROFILING IN THE PROGRESSION OF MULTIPLE SCLEROSIS: DEVELOPMENT OF NOVEL BIOMARKER TO ASSESS DISEASE SEVERITY AND THERAPEUTIC REGIMEN
Funder
National Health and Medical Research Council
Funding Amount
$450,750.00
Summary
A metabolic process known as the kynurenine pathway (KP) has been found to be dysregulated in multiple sclerosis (MS) patients. We are currently investigating which components of the KP is impaired that put MS patients in jeopardy. Next, we aim to use specific drugs known to manipulate the KP in order to rectify the impairment and stop MS. Outcome of this study may potentially lead to discovery of new biomarkers to assess severity of MS progression and also novel therapeutic regimen.
Neuregulin 1 Type III Overexpression And Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$651,966.00
Summary
Neuregulin (NRG1) is a neuronal growth factor and regulates the development of cortical inhibitory interneurons. Human studies suggest that NRG1 type III overexpression and deficient interneuron development underlie schizophrenia. Thus, we have developed a mouse overexpressing Nrg1 type III to discover mechanisms behind NRG1-related cortical pathology and schizophrenia-like behaviours and to clarify whether NRG1 type III interacts with environmental risk factors for the disorder.
The Involvement Of The Kynurenine Pathway In Blood Brain Barrier Disruption And Its Relevance For Neuroinflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$597,797.00
Summary
We aim to study the involvement of molecules deriving from the degradation of the essential amino acid tryptophan on the breakdown of the ñblood-brain barrierî (the cellular wall separating blood and brain) that is observed in several major brain diseases. Using specific drugs blocking the production or the effects of these toxic compounds we expect to be able to preserve the integrity of the blood brain barrier and so to limit brain inflammation and neuronal loss.
Extracellular Acidification And Its Role In Disease
Funder
National Health and Medical Research Council
Funding Amount
$371,529.00
Summary
This proposal focuses on the diseases cystic fibrosis and acute pancreatitis for which there are currently no treatments. In both diseases the affected organs become strongly acidic. Furthermore, these acid changes can be causal in disease progression. However, the source of this acidification is remains unknown. We will identify the routes of acid secretion, the causal role of acidification in disease progression and the effectiveness of treatments aimed at restoring acid-base balance.
Pharmacological Development Of A Stable Cytochrome P450-mediated Omega-3 Fatty Acid Epoxide Analogue As A Novel Anti-metastatic Agent
Funder
National Health and Medical Research Council
Funding Amount
$599,847.00
Summary
Dietary ?-3 fatty acids decrease the risk of cancer metastasis. We have found that a certain ?-3 fatty acid metabolite inhibits tumour cell migration but is too unstable to be a useful drug. We have now prepared a stable version of this metabolite for in vivo use as a potential anti-metastatic drug. In this project we will define the mechanism of action of this novel agent and evaluate how it may be best used in patient treatments by testing in a range of in vivo animal models of metastasis.
Using Artificial Synapses To Investigate The Functional Pathology Underlying Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$515,256.00
Summary
Epilepsy is a common neurological disorder. Some forms arise from hereditary mutations to GABA-A receptors. To advance our understanding of epileptogenesis, it is necessary to understand how mutations affect GABA-AR function. We will use a novel ‘artificial synapse’ system to characterise these mutant receptors. This will define how epilepsy is caused and inform us how to best tailor drug treatments for different epilepsy conditions.
Oxytocin As A Novel Antagonist Of The Intoxicating And Addictive Effects Of Alcohol
Funder
National Health and Medical Research Council
Funding Amount
$739,106.00
Summary
Alcohol is Australia’s most harmful recreational drug and more effective treatments for alcohol abuse are desperately needed. The CIs have shown that administering oxytocin reduces alcohol intoxication and consumption, and prevents alcohol from acting at specific sites in the brain that are central to alcohol’s intoxicating and addictive effects. This project probes the effects of oxytocin at these sites and the potential utility of targeting this interaction to treat alcohol-use disorders.
Modifying Brain Excitabilty By Upregulating The KCC2 Chloride Transporter
Funder
National Health and Medical Research Council
Funding Amount
$535,662.00
Summary
Brain activity depends upon the fine balance between neuronal excitation and inhibition. When this balance is lost, debilitating seizures can result, such as occurs in epilepsy. We have developed a new gene manipulation approach to enhance neuronal inhibition and prevent seizures in mice. We will examine the physiological mechanisms underlying this effect, and we propose that we can also use this genetic switch to stop the progression into epilepsy that occurs following a brain trauma.
Control Of Anabolic And Catabolic Pathways By AMPK
Funder
National Health and Medical Research Council
Funding Amount
$946,402.00
Summary
This project focuses on the role of the metabolic stress-sensing enzyme AMP-activated protein kinase (AMPK) in the control of glucose and fat metabolism. AMPK has been linked to the regulation of exercise capacity, longevity and the control of insulin sensitivity. This is important for our understanding of the metabolic dimensions of our Nations most important health problems including, type-2 diabetes, cardiovascular disease, obesity, neurodegeneration as well as other age onset diseases.