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Inhibitors Of Secretory Phospholipases In Diet Induced Obese Rats
Funder
National Health and Medical Research Council
Funding Amount
$581,051.00
Summary
A new drug given to rats fed a high fat-carbohydrate diet shows very promising effects in preventing and treating abdominal obesity, insulin resistance, glucose intolerance, and other risk factors for diabetes and cardiovascular disease. This project will profile biochemical and pharmacological properties of the drug in more detail in order to track down molecular mechanisms of its action and potential therapeutic benefits, guided by studies on rats, biochemical markers, rat and human fat cells.
Improving Endothelial Dysfunction In Diabetes-associated Vascular Diseases With Nrf2 Activators
Funder
National Health and Medical Research Council
Funding Amount
$340,039.00
Summary
Diabetic patients have a greater risk of developing cardiovascular diseases as compared to the general population. This is largely attributed to the impact the diabetic environment has on the endothelium (inner layer of the blood vessel). Indeed, clinical studies have shown that impaired endothelial function occurs prior to the development of cardiovascular diseases. Hence, we propose to study a novel way to improve endothelial function by limiting oxidative stress and inflammatory pathways.
Investigating the functional interaction between vasopressin and angiotensin receptors. Kidney disease resulting from diabetes is a major health issue for Australians, and indigenous Australians in particular. This project aims to enable improved therapies to be developed, as well as better inform doctors regarding the use of potential combinations of existing pharmaceuticals to treat this condition.
Understanding The Physiological Consequences Of Biased Signalling Mediated By The Glucagon-like Peptide-1 Receptor
Funder
National Health and Medical Research Council
Funding Amount
$636,508.00
Summary
The glucagon-like peptide 1 receptor is a major target for treatment of Type 2 diabetes and obesity. However, the development of drugs targeting this receptor is challenging as activation by different ligands can result in distinct signalling biases, a paradigm for which there is limited understanding of the physiological consequences. This project will address this critical knowledge gap and may allow for development of novel drugs with improved therapeutic outcomes.
Understanding Allosteric Modulation And Biased Signalling At Family B GPCRs
Funder
National Health and Medical Research Council
Funding Amount
$428,065.00
Summary
Family B GPCRs are therapeutic targets for drugs treating osteoporosis, hypercalcaemia, Paget’s disease, type II diabetes and are being actively pursued for other diseases that represent major global health burdens. Despite huge financial input, there are no orally available drugs that act on these receptors. This speaks to a lack of mechanistic understanding of how they work. My research focuses on addressing this question and how to exploit these receptors to design and identify better drugs.
G Protein-Coupled Receptors (GPCRs) form the largest family of receptors and drug targets in living organisms. Currently, the major reason that new drugs fail to reach the clinic is lack of appropriate drug effect (approx. 30%). Thus, we need a better understanding of how GPCRs work and how this relates to disease. Work within my fellowship will address this knowledge gap, using GPCR models that are relevant to treatment of metabolic, inflammatory, cardiovascular and central nervous system disea ....G Protein-Coupled Receptors (GPCRs) form the largest family of receptors and drug targets in living organisms. Currently, the major reason that new drugs fail to reach the clinic is lack of appropriate drug effect (approx. 30%). Thus, we need a better understanding of how GPCRs work and how this relates to disease. Work within my fellowship will address this knowledge gap, using GPCR models that are relevant to treatment of metabolic, inflammatory, cardiovascular and central nervous system disease.Read moreRead less
Novel sources of nitric oxide (NO) in cells: Implications for an endocrine role for NO. Communication between cells is essential for coordinating and controlling a healthy body. A key regulator and cell-communicating molecule is the gas, nitric oxide. Although nitric oxide is a simple substance we still do not fully understand all aspects of its cellular functions. It is assumed that nitric oxide is synthesised in the body and, after release, is rapidly metabolized and eliminated. Reductions in ....Novel sources of nitric oxide (NO) in cells: Implications for an endocrine role for NO. Communication between cells is essential for coordinating and controlling a healthy body. A key regulator and cell-communicating molecule is the gas, nitric oxide. Although nitric oxide is a simple substance we still do not fully understand all aspects of its cellular functions. It is assumed that nitric oxide is synthesised in the body and, after release, is rapidly metabolized and eliminated. Reductions in the levels of nitric oxide in the body are associated with several diseases states and states of dysfunction including cardiovascular disease, diabetes and also impotence. Professor Triggle's study seeks to characterize how tissues may store nitric oxide, thus prolonging the life of nitric oxide, and how such stores are released. Read moreRead less
Molecular Characterisation Of The Glucagon-like Peptide 1 Receptor
Funder
National Health and Medical Research Council
Funding Amount
$681,953.00
Summary
The glucagon-like peptide 1 receptor is a major target for treatment of Type 2 diabetes and obesity. However, the development of drugs for this receptor is challenging due to limited understanding of potential sites of drug interaction and how individual drugs may differentially change signalling from the receptor. This project will address these critical knowledge gaps, which may allow for improved therapeutic outcomes.
Pharmacological Investigation Of The Glucagon-Like Peptide-1 Receptor (GLP-1R)
Funder
National Health and Medical Research Council
Funding Amount
$367,948.00
Summary
Family B G protein-coupled receptors represent key therapeutic targets for many conditions, including metabolic, bone, growth and neuronal disorders. However, poor mechanistic understanding of this receptor family impacts on their clinical value. Consequently, this research is aimed at gaining a more comprehensive understanding of the structure and function of the family B glucagon-like peptide-1 receptor through use of new and novel pharmacological techniques.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0883078
Funder
Australian Research Council
Funding Amount
$356,000.00
Summary
Liquid Chromatography Tandem Mass Spectrometry Steroid Analysis Facility. This first of a new generation of ultra-sensitive analytical mass spectrometers for small molecules will be established as a national assay facility allowing all Australian researchers open access to a new dimension of highly accurate and simultaneous measurements of multiple bodily chemicals such as steroids, vitamins and hormones. It is crucial to developing new knowledge in basic, developmental and pathological cell bio ....Liquid Chromatography Tandem Mass Spectrometry Steroid Analysis Facility. This first of a new generation of ultra-sensitive analytical mass spectrometers for small molecules will be established as a national assay facility allowing all Australian researchers open access to a new dimension of highly accurate and simultaneous measurements of multiple bodily chemicals such as steroids, vitamins and hormones. It is crucial to developing new knowledge in basic, developmental and pathological cell biology and for underpinning commercial developments of new molecular targets for therapeutic drugs for many diseases including cancer, cardiovascular disease and reproductive disorders. This facility is pivotal to maintaining international competitiveness in many areas of biological research in national priority areas.Read moreRead less