Functional and structural diversity of the cathepsin L peptidase from the human blood fluke Schistosoma mansoni. Peptidases are enzymes that are important in many infectious and physiological disease states. For example, they are used by infectious pathogens to enter human tissues and survive inside their bodies. The same type of enzymes also contribute to tissue damage in many pathological processes in humans such as cancer, arithritis and osteoporosis. There is an urgent need to define their s ....Functional and structural diversity of the cathepsin L peptidase from the human blood fluke Schistosoma mansoni. Peptidases are enzymes that are important in many infectious and physiological disease states. For example, they are used by infectious pathogens to enter human tissues and survive inside their bodies. The same type of enzymes also contribute to tissue damage in many pathological processes in humans such as cancer, arithritis and osteoporosis. There is an urgent need to define their structure and properties so that we can employ rational approaches to develop new drugs that can combat these diseases and ailments. Read moreRead less
Aminopeptidases involved in regulating the amino acid pool in malaria parasites. Aminopeptidases are pivotal to the normal functions of all cells. Abnormalities in their function and/or structure results in tissue damage in many pathological processes in humans such as cancer, neuronal diseases and hormonal action. They are also critical to viral, bacterial and parasitic infections as they are employed to remove amino acids from the host for use in building their own proteins. This project bring ....Aminopeptidases involved in regulating the amino acid pool in malaria parasites. Aminopeptidases are pivotal to the normal functions of all cells. Abnormalities in their function and/or structure results in tissue damage in many pathological processes in humans such as cancer, neuronal diseases and hormonal action. They are also critical to viral, bacterial and parasitic infections as they are employed to remove amino acids from the host for use in building their own proteins. This project brings national and international expertise together to define the structure and biological properties of these essential enzymes so that in the future we can employ rational approaches to develop new drugs that can combat these diseases and ailments.Read moreRead less
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.
Identification of functionally important autophosphorylation site(s) on ataxia telangiectasia and Rad 3 - related (ATR) protein kinase. The integrity of our genetic material must be maintained so that it can be passed on from one generation to the next and also to minimize the risk of cancer and other pathologies in an individual. There are multiple proteins involved in protecting our DNA including several enzymes that detect and signal DNA damage to a series of pathways involved in halting the ....Identification of functionally important autophosphorylation site(s) on ataxia telangiectasia and Rad 3 - related (ATR) protein kinase. The integrity of our genetic material must be maintained so that it can be passed on from one generation to the next and also to minimize the risk of cancer and other pathologies in an individual. There are multiple proteins involved in protecting our DNA including several enzymes that detect and signal DNA damage to a series of pathways involved in halting the passage of cells through the cell cycle so that repair can occur. This project studies the mechanism of action of one of these enzymes which will be of benefit in designing new compounds to fight disease. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE150100149
Funder
Australian Research Council
Funding Amount
$590,000.00
Summary
Reaching new heights in high-resolution electron microscopy . High-resolution electron microscopy (EM): Direct electron detection cameras are a recent technological breakthrough delivering one of the greatest single advancements to the field of molecular cryo-EM. The aim of this project is to enable a 'first of a kind' cryo-EM platform in Australia enabling high-throughput atomic resolution protein structure determination. This will be achieved by integrating a state-of-the-art Gatan K2 Summit D ....Reaching new heights in high-resolution electron microscopy . High-resolution electron microscopy (EM): Direct electron detection cameras are a recent technological breakthrough delivering one of the greatest single advancements to the field of molecular cryo-EM. The aim of this project is to enable a 'first of a kind' cryo-EM platform in Australia enabling high-throughput atomic resolution protein structure determination. This will be achieved by integrating a state-of-the-art Gatan K2 Summit Direct Electron Detection camera system into the established cryo-EM facility managed by the University of Queensland node of the Australian Microscopy and Microanalysis Facility. This will offer unique and significantly improved capabilities for atomic resolution protein structure analysis, and will support a broad range of projects across the biological sciences.Read moreRead less
Novel human tryptases: their potential role in inflammatory diseases of the young and old. We have discovered a number of novel human tryptases, and while other members of this enzyme family have been implicated in the development of inflammatory diseases (including rheumatoid arthritis), little is known about these new molecules. We aim to characterise these new enzymes by determining what part of the body they are produced in, whether they are associated with specific inflammatory diseases, an ....Novel human tryptases: their potential role in inflammatory diseases of the young and old. We have discovered a number of novel human tryptases, and while other members of this enzyme family have been implicated in the development of inflammatory diseases (including rheumatoid arthritis), little is known about these new molecules. We aim to characterise these new enzymes by determining what part of the body they are produced in, whether they are associated with specific inflammatory diseases, and what target molecules they act on. A better understanding of these factors will increase the chances of finding cures and developing better treatments for important inflammatory diseases of the ageing population.Read moreRead less
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