Chemical synthesis of cancer-associated glycoproteins. Glycosylation of proteins is an extremely common event which plays an important role in a variety of biological processes. Aberrant glycosylation and over-production of glycoproteins is associated with numerous cancer types (including breast, prostate, ovarian and small lung) and are recognised as promising agents for disease diagnosis and vaccine development. A range of cancer-associated glycoproteins will be synthesised in this research p ....Chemical synthesis of cancer-associated glycoproteins. Glycosylation of proteins is an extremely common event which plays an important role in a variety of biological processes. Aberrant glycosylation and over-production of glycoproteins is associated with numerous cancer types (including breast, prostate, ovarian and small lung) and are recognised as promising agents for disease diagnosis and vaccine development. A range of cancer-associated glycoproteins will be synthesised in this research program using a number of novel chemical technologies. These glycoproteins will be used to develop cancer vaccines and diagnostics. Cancer is a severe burden on the Australian community and on the economy, therefore this research will be of significant benefit to Australia.Read moreRead less
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
Enhancing the performance of existing industrial enzymes through the application of new chemical modification technology. Enzymes have many uses in industry, replacing undesirable chemicals which adversely effect human & animal health & the environment. Enzymes offer advantages in effectiveness, biodegradability, specificity and safety. The concern with enzymes, in industrial applications, is that enzyme performance is degraded by a harsh chemical and/or physical environment. The aim of this stu ....Enhancing the performance of existing industrial enzymes through the application of new chemical modification technology. Enzymes have many uses in industry, replacing undesirable chemicals which adversely effect human & animal health & the environment. Enzymes offer advantages in effectiveness, biodegradability, specificity and safety. The concern with enzymes, in industrial applications, is that enzyme performance is degraded by a harsh chemical and/or physical environment. The aim of this study is to improve the performance of industrially significant enzymes by enhancing resistance to chemical & physical degradation or inactivation. This will be achieved by modifying the enzymes using new technology that we have developed. This will improve cost effectiveness of existing industrial enzymes & create opportunities for new uses of enzymes.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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The control of elongation factor 2 and its role in the regulation of protein synthesis. Protein synthesis is a key process in living cells. The main stage, elongation, is regulated through phosphorylation of elongation factor eEF2 in response to hormones, amino acids and cellular energy status, via changes in the activity of eEF2 kinase. We will study how these conditions control eEF2 kinase by studying its phosphorylation and identifying new kinases that regulate it. We will explore the role of ....The control of elongation factor 2 and its role in the regulation of protein synthesis. Protein synthesis is a key process in living cells. The main stage, elongation, is regulated through phosphorylation of elongation factor eEF2 in response to hormones, amino acids and cellular energy status, via changes in the activity of eEF2 kinase. We will study how these conditions control eEF2 kinase by studying its phosphorylation and identifying new kinases that regulate it. We will explore the role of eEF2 in controlling protein synthesis, seek new substrates for eEF2 kinase and initiate work to elucidate the structure of this unusual enzyme. This will enhance, in a range of ways, fundamental understanding of cell physiology.Read moreRead less
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
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
Australian Laureate Fellowships - Grant ID: FL140100027
Funder
Australian Research Council
Funding Amount
$2,898,150.00
Summary
Under the hood: single-molecule studies of multi-protein machines. Under the hood: single-molecule studies of multi-protein machines. Living cells are filled with complex protein machines that are responsible for the molecular processes supporting life. This project is aimed towards the development of physical tools that enable the study of these protein complexes at the level of single molecules. This project aims to study the protein machinery responsible for DNA replication, the process of du ....Under the hood: single-molecule studies of multi-protein machines. Under the hood: single-molecule studies of multi-protein machines. Living cells are filled with complex protein machines that are responsible for the molecular processes supporting life. This project is aimed towards the development of physical tools that enable the study of these protein complexes at the level of single molecules. This project aims to study the protein machinery responsible for DNA replication, the process of duplicating genomic information before cell division. By making real-time single-molecule movies of the replication process, this project aims to unravel the molecular mechanisms of this important process and provide the knowledge required to understand disease mechanisms and catalyse drug development.Read moreRead less