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
Allosteric regulation, molecular structure and function of transglutaminase 2. With Australia's ageing population, we can expect to see increasing prevalence of pathologies such as cancer, Alzheimer's disease, and cataracts. The ubiquitous enzyme transglutaminase 2 (TG2) has been implicated in all of these age-related diseases, as well as in chronic disorders such as coeliac disease and diabetes, and may contribute in a positive way to wound healing. Understanding how TG2 is activated and inac ....Allosteric regulation, molecular structure and function of transglutaminase 2. With Australia's ageing population, we can expect to see increasing prevalence of pathologies such as cancer, Alzheimer's disease, and cataracts. The ubiquitous enzyme transglutaminase 2 (TG2) has been implicated in all of these age-related diseases, as well as in chronic disorders such as coeliac disease and diabetes, and may contribute in a positive way to wound healing. Understanding how TG2 is activated and inactivated, and how it selects its targets, will be a critical addition to current knowledge of this enzyme, and will be an essential prerequisite for the development of TG2-targetted drugs and other TG2-related therapies.Read moreRead less
Guarding and evolving the genome: interactions between DNA-repair enzymes and damaged DNA. The application of structural biology techniques to the area of DNA repair allows us to understand the full implications linking genes and proteins to the molecular mechanisms of diseases such as cancer and hereditory conditions. Studies in this highly internationally competitive area are already established in the Bond laboratory, which has recently relocated to Australia. The use of forward-thinking stru ....Guarding and evolving the genome: interactions between DNA-repair enzymes and damaged DNA. The application of structural biology techniques to the area of DNA repair allows us to understand the full implications linking genes and proteins to the molecular mechanisms of diseases such as cancer and hereditory conditions. Studies in this highly internationally competitive area are already established in the Bond laboratory, which has recently relocated to Australia. The use of forward-thinking structural biology approaches to solve difficult technical problems will foster collaborations within Australia and with leading laboratories abroad, providing excellent up-to-date research training for students and postdoctoral researchers.
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