Discovery Early Career Researcher Award - Grant ID: DE180101165
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Structural insights into adenosine receptors. This project aims to investigate mechanisms underlying ligand binding and signal transduction at G protein-coupled receptors (GPCRs) by utilising the adenosine receptor family as a model system. This interdisciplinary project will use structural biology, pharmacology and biochemistry. The expected outcomes include understanding ligand selectivity across the four adenosine receptor family members. This should provide significant benefits, such as adva ....Structural insights into adenosine receptors. This project aims to investigate mechanisms underlying ligand binding and signal transduction at G protein-coupled receptors (GPCRs) by utilising the adenosine receptor family as a model system. This interdisciplinary project will use structural biology, pharmacology and biochemistry. The expected outcomes include understanding ligand selectivity across the four adenosine receptor family members. This should provide significant benefits, such as advancement of fundamental knowledge that could also lead to therapeutic development.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE130100117
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Allosteric fingerprinting of G protein-coupled receptor monomers and oligomers. Allosteric modulation describes interactions between distinct, but conformationally linked, binding sites. Research will develop enabling technology using the unique profile, or 'fingerprint', of allosteric modulation at interacting and non-interacting G protein-coupled receptors to probe for receptor complexes within healthy and diseased tissue.
Discovery Early Career Researcher Award - Grant ID: DE200101511
Funder
Australian Research Council
Funding Amount
$424,816.00
Summary
Structural insights into activation, dynamics and bias of GPCRs. The project aims to investigate the mechanisms underlying activation, biased agonism and G protein selectivity of G protein-coupled receptors (GPCRs) by utilising the adenosine A1 receptor as a model system. This project expects to generate knowledge in the area of GPCR biology using an interdisciplinary approach including structural biology, pharmacology, biochemistry and protein engineering. The expected outcomes include (i) unde ....Structural insights into activation, dynamics and bias of GPCRs. The project aims to investigate the mechanisms underlying activation, biased agonism and G protein selectivity of G protein-coupled receptors (GPCRs) by utilising the adenosine A1 receptor as a model system. This project expects to generate knowledge in the area of GPCR biology using an interdisciplinary approach including structural biology, pharmacology, biochemistry and protein engineering. The expected outcomes include (i) understanding the structural mechanisms underlying GPCR activation, (ii) biased agonism and (iii) G protein selectivity. This should provide significant benefits, such as advancement of fundamental knowledge in GPCR biology and pharmacology that could also one day lead to therapeutic development.Read moreRead less
Molecular mechanisms of cyclic Adenosine Monophosphate (AMP) induced apoptosis. Cyclic Adenosine Monophosphate (cAMP) is an important cellular chemical necessary for cell growth. However, de-regulated cAMP production in response to altered physiology can result in cellular death or apoptosis. This is attributed to the development of certain human diseases and this project aims to understand the molecular mechanism behind this process.
How cholesterol optimises ion pump function in animal membranes. This project aims to determine how cholesterol optimises ion pump function in animal membranes and to identify the major effects of cholesterol and its derivatives on membranes’ physical properties. All animal cells need high levels of cholesterol in the plasma membrane for survival. Insufficient cholesterol biosynthesis leads to severe birth defects. The need for cholesterol is likely linked to its acceleration of sodium pump acti ....How cholesterol optimises ion pump function in animal membranes. This project aims to determine how cholesterol optimises ion pump function in animal membranes and to identify the major effects of cholesterol and its derivatives on membranes’ physical properties. All animal cells need high levels of cholesterol in the plasma membrane for survival. Insufficient cholesterol biosynthesis leads to severe birth defects. The need for cholesterol is likely linked to its acceleration of sodium pump activity, essential to physiological processes including cell division, nerve, muscle and kidney activity. An expected benefit of the project is knowledge on the molecular origin of diseases associated with inhibition of cholesterol production, and a more complete understanding of the crucial role played by cholesterol via its effect on ion pumping towards the healthy functioning of vital organs, particularly in heart muscle and nerves.Read moreRead less
Lipid-protein interplay in the mechanism of the sodium pump. The sodium pump is the major energy-consuming enzyme of animal cells. Its ion pumping is essential to numerous physiological processes (e.g. nerve, muscle and kidney activity and the maintenance of cell volume). Because of its importance in so many cell functions, the enzyme must be able to respond to cellular conditions. Using measurements of the enzyme's activity in isolated membrane fragments and comparison with its behaviour in liv ....Lipid-protein interplay in the mechanism of the sodium pump. The sodium pump is the major energy-consuming enzyme of animal cells. Its ion pumping is essential to numerous physiological processes (e.g. nerve, muscle and kidney activity and the maintenance of cell volume). Because of its importance in so many cell functions, the enzyme must be able to respond to cellular conditions. Using measurements of the enzyme's activity in isolated membrane fragments and comparison with its behaviour in living cells, this project aims to determine how sodium pump activity is modulated by transmembrane electric potential and intramembrane electric field strength. Our project could provide fundamental new knowledge on how membrane protein function in general can be controlled by electrical properties of their lipid surroundings.Read moreRead less
Structural basis of gating in hERG potassium ion channel proteins. This project aims to use cryo-electron microscopy to determine atomic resolution structures of open, closed and inactivated states of an ion channel important for regulating activity in the heart and the brain. This work will provide fundamental insights into how ion channel proteins utilise electrochemical energy to mechanically open and close gates that regulate ion flow across cell membranes. Electrical signalling is ubiquitou ....Structural basis of gating in hERG potassium ion channel proteins. This project aims to use cryo-electron microscopy to determine atomic resolution structures of open, closed and inactivated states of an ion channel important for regulating activity in the heart and the brain. This work will provide fundamental insights into how ion channel proteins utilise electrochemical energy to mechanically open and close gates that regulate ion flow across cell membranes. Electrical signalling is ubiquitous in biology but is of particular importance in the brain and heart where ion channels are important therapeutic targets for cardiovascular and psychiatric diseases. Read moreRead less
Electrochemical biosensors for detection of cardiac disease markers in blood. Cardiovascular diseases leading to heart failure have a prevalence of over 16 per cent in Australia. The social, economic and health burden is higher than for any other disease group. Hence, it is critically important to develop fit-for-purpose sensors of known cardiac biomarkers, which alert patients and clinicians of the risk of imminent heart failure.