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
High-throughput single-molecule directed evolution. DNA polymerases are essential enzymes in many biotechnological tools, including DNA sequencing and PCR tests. However, existing DNA polymerases have limitations, resulting in inaccuracies and inefficiencies. Existing methods to improve polymerases lack sensitivity to screen for subtle, yet pivotal traits. This project aims to overcome this limitation by developing a new single-molecule directed-evolution system to evolve better polymerases. Wit ....High-throughput single-molecule directed evolution. DNA polymerases are essential enzymes in many biotechnological tools, including DNA sequencing and PCR tests. However, existing DNA polymerases have limitations, resulting in inaccuracies and inefficiencies. Existing methods to improve polymerases lack sensitivity to screen for subtle, yet pivotal traits. This project aims to overcome this limitation by developing a new single-molecule directed-evolution system to evolve better polymerases. With this new technology we aim to identify DNA polymerases with improved performance that benefit biotechnological applications. Additionally, these single-molecule directed-evolution methods will benefit the wider scientific community and lay the foundation for further advances in directed evolution.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
Roadblocks in DNA replication. This project aims to develop the technology to visualise and understand the molecular processes responsible for the faithful copying of cellular DNA in the presence of roadblocks caused by chemical pressures and competing intracellular events. Understanding this process is important as DNA replication is responsible for copying the DNA genetic blueprint of cells and is crucial to all life on earth. This project will have as key outcomes the development of novel mol ....Roadblocks in DNA replication. This project aims to develop the technology to visualise and understand the molecular processes responsible for the faithful copying of cellular DNA in the presence of roadblocks caused by chemical pressures and competing intracellular events. Understanding this process is important as DNA replication is responsible for copying the DNA genetic blueprint of cells and is crucial to all life on earth. This project will have as key outcomes the development of novel molecular visualisation technology and the first molecular description of the dynamic processes used by the DNA-replication machinery to navigate roadblocks. These outcomes should provide significant benefits including enhanced collaboration and scientific capacity in Australia.Read moreRead less