Harnessing Tyrosine Metabolism To Combat Respiratory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$866,467.00
Summary
Cross-talk between our immune system and the microbiome is central to health and disease. In particular, the gut microbiome has wide-ranging effects throughout the body, in part through the production of metabolites with immunomodulatory activity. We have discovered a novel subset of microbial metabolites which can protect mice against allergic airway inflammation, a model of asthma. We now aim to discovery how these metabolites work with a view towards developing them as therapeutics.
Presentation Of Metabolite Antigens By MR1 Molecules: A Fundamental System Of Immune Priming
Funder
National Health and Medical Research Council
Funding Amount
$883,832.00
Summary
Our immune system constantly monitors our body for disease-causing microbes, such as bacteria that cause illnesses like pneumonia or tuberculosis. Our cells have a molecular alarm-system called 'MR1' which alerts white blood cells that an infection by microbes is occurring, however this process is not well understood. This grant will allow me to discover the cells and molecular pathways that govern the MR1 alarm system, which may lead to new treatments against common diseases in our community.
The body’s normal function depends upon maintaining energy balance matching demand and supply. The body senses its energy status by monitoring metabolite concentrations. I have discovered a metabolite that controls multiple enzymes critical for energy homeostasis and appetite in the body that may provide new approaches to tackle obesity related disease. I have found the metabolite-binding pocket in many proteins and it may represent a major new regulatory network.
The dramatic increase in obesity and age-related metabolic disorders demonstrates the importance of gaining a better understanding of how cells and organisms regulate their energy stores. This project will identify novel molecular mechanisms that control the enzyme CaMKK2, which is a key regulator of whole-body energy metabolism. This will provide new opportunities to inform more effective strategies to tackle metabolic diseases, and improve health in an increasingly ageing population.
Polymicrobial Interactions In Chronic Periodontitis
Funder
National Health and Medical Research Council
Funding Amount
$413,133.00
Summary
In this study we will determine how three pathogenic species of bacteria interact. Together these species are associated with periodontitis and they produce toxic compounds that may cause tissue damage. Using the newly emerging technologies of metabolomics and transcriptomics we will characterise these interactions. This will identify potential diagnostic biomarkers of disease and therapeutic targets.
The Role Of Cytochrome P-450 Metabolites Of Arachidonic Acid In Human Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$552,610.00
Summary
Alcohol consumption is known to raise blood pressure but the mechanism by which it does this is not known This project examines the role of certain fatty acid metabolites called cytochrome P450 metabolites of arachidonic acid (CYP450AA-M) during periods of alcohol consumption and periods of abstinance from alcohol. These fatty acid metabolites act on blood vessels causing them to constrict or dilate. In doing this they affect blood pressure regulation. The results of this study will determine ho ....Alcohol consumption is known to raise blood pressure but the mechanism by which it does this is not known This project examines the role of certain fatty acid metabolites called cytochrome P450 metabolites of arachidonic acid (CYP450AA-M) during periods of alcohol consumption and periods of abstinance from alcohol. These fatty acid metabolites act on blood vessels causing them to constrict or dilate. In doing this they affect blood pressure regulation. The results of this study will determine how important CYP450AA-M are in the development of alcohol related hypertension. We will study CYP450AA-M in cells as well as in plasma and urine to see if cellular levels of CYP450AA-M are better determinants of blood pressure regulation than plasma or urinary levels of CYP450AA-M. This project will help scientists decide how important these metabolites are for blood presssure regulation. If these metabolites are found to be important then it should be possible to alter their levels either by diet or drug treatment.Read moreRead less