Function and regulation of the Na+,K+-ATPase. The Na+,K+-ATPase is the major energy-consuming enzyme of animal cells. Its ion pumping is essential for numerous physiological functions (e.g. heart, kidney, brain). Molecular detail of its pumping mechanism is, however, lacking and its regulation is still unclear. We will use rapid reaction methods on purified enzyme in vitro to locate the rate-determining step of the enzyme cycle, determine its mechanism, investigate its regulation by sodium conce ....Function and regulation of the Na+,K+-ATPase. The Na+,K+-ATPase is the major energy-consuming enzyme of animal cells. Its ion pumping is essential for numerous physiological functions (e.g. heart, kidney, brain). Molecular detail of its pumping mechanism is, however, lacking and its regulation is still unclear. We will use rapid reaction methods on purified enzyme in vitro to locate the rate-determining step of the enzyme cycle, determine its mechanism, investigate its regulation by sodium concentration, phosphorylation and membrane composition, and isolate its charge-transporting steps. The results will have immediate impact on the understanding of the enzyme's mechanism, its metabolic control and its role in disease.Read moreRead less
Novel mass spectrometry methods to assess cellular oxidative stress. This project will provide fundamental understanding to the biology of cell stress that may lead to novel approaches for treating age-related diseases. It has the potential to have a significant economic and social impact nationally and internationally and provide Australian scientists with new technologies to study challenging issues in biology.
Discovery Early Career Researcher Award - Grant ID: DE190100668
Funder
Australian Research Council
Funding Amount
$422,574.00
Summary
Cysteamine dioxygenases: novel oxygen sensors implicated in hypoxia? This project aims to characterise and manipulate a novel oxygen sensing system, the cysteamine dioxygenases, to help understand how mammalian cells respond to low oxygen concentrations, a condition known as hypoxia. A number of the world’s most destructive diseases can impair oxygen delivery, altering biochemical landscapes. By understanding how cells respond to fluctuations in oxygen, the project expects to develop effective m ....Cysteamine dioxygenases: novel oxygen sensors implicated in hypoxia? This project aims to characterise and manipulate a novel oxygen sensing system, the cysteamine dioxygenases, to help understand how mammalian cells respond to low oxygen concentrations, a condition known as hypoxia. A number of the world’s most destructive diseases can impair oxygen delivery, altering biochemical landscapes. By understanding how cells respond to fluctuations in oxygen, the project expects to develop effective methods to treat these detrimental conditions. Characterisation of the cysteamine dioxygenases could establish a novel mechanism by which cells monitor changes in oxygen, assisting in understanding hypoxia and disease. The project will also enable new cysteine initiating substrates to be identified, allowing the full impact of this regulatory process to be appreciated in mammals.Read moreRead less
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
Heme oxygenase integrates cellular responses to oxygen stress. A deficiency in the protein heme oxygenase-1 causes severe biological consequences including retarded development, chronic inflammation and increased susceptibility to age-associated diseases. By illuminating how heme oxygenase-1 improves cell function the project will eventually assist in preventing or slowing the serious age-associated disorders.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100181
Funder
Australian Research Council
Funding Amount
$650,000.00
Summary
Strengthening merit-based access and support at the new National Computing Infrastructure petascale supercomputing facility. World-leading high-performance computing is fundamental to Australia's international research success. This facility will provide access to the new National Computational Infrastructure facility by world-leading researchers from six research universities, and sustain ground-breaking work in an increasingly competitive environment.