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
The Effect Of Cytochrome P450 Genotype On Blood Pressure And 20-HETE Responses To Lifestyle Interventions
Funder
National Health and Medical Research Council
Funding Amount
$743,665.00
Summary
The effectiveness of treatments to reduce heart disease risk can vary enormously between individuals. This is partly due to a persons genetic makeup. Fatty acid metabolites called cytochrome P450 metabolites of arachidonic acid (CYP450-AAM) can act on blood vessels and the kidney to regulate blood pressure. We will study the effect of having a variation in a gene that regulates CYP450-AAM on blood pressure and heart disease risk in combination with a high salt diet or weight reduction.