Predicting Drug-drug Interactions Due To Tyrosine Kinase Inhibitors: Inhibition Of Drug Metabolising Enzymes And Transporters
Funder
National Health and Medical Research Council
Funding Amount
$535,495.00
Summary
Tyrosine kinase inhibitors (TKIs) are a new class of anticancer agents. Cancer patients typically receive multiple drugs, for the treatment of cancer and other diseases, increasing the probability of interactions between coadministered drugs. Despite the widespread use of TKIs, their potential to cause drug interactions is poorly understood. Using novel in vitro approaches, this project will identify drug interactions precipitated by TKIs thereby improving drug efficacy and patient safety.
Synthesis of substrate analogues for probing catalytic mechanisms and specificity of enzymes involved in the metabolism of plant polysaccharides. The project is aimed at strengthening collaborations between research groups in Adelaide and France, with the specific objective of synthesizing substrate analogues as probes of enzymatic mechanisms and substrate specificity in polysaccharide hydrolases and synthases of barley. The chemical expertise resides in France, while the enzymatic work will be ....Synthesis of substrate analogues for probing catalytic mechanisms and specificity of enzymes involved in the metabolism of plant polysaccharides. The project is aimed at strengthening collaborations between research groups in Adelaide and France, with the specific objective of synthesizing substrate analogues as probes of enzymatic mechanisms and substrate specificity in polysaccharide hydrolases and synthases of barley. The chemical expertise resides in France, while the enzymatic work will be conducted largely in Australia. Exchange of research staff, particularly at the postgraduate student and research associate levels, is considered essential to capture the benefits of the complementary expertise and to extend an existing international collaboration. The target enzymes are of central importance in cell wall metabolism during development of higher plants.Read moreRead less
How Does Inflammation Of The Gut Change Its Sensory Innervation?
Funder
National Health and Medical Research Council
Funding Amount
$613,767.00
Summary
A large number of patients that are referred to gastroenterologists for pain and discomfort from the bowel are offered no effective treatment. This has a large impact on quality of life and often involves invasive tests to rule out inflammatory or cancerous causes. These patients are classified as suffering from irritable bowel syndrome (IBS). Patients who have diagnosable inflammatory bowel disease (IBD) where colonoscopy is positive may suffer similar symptoms but also have no treatment for th ....A large number of patients that are referred to gastroenterologists for pain and discomfort from the bowel are offered no effective treatment. This has a large impact on quality of life and often involves invasive tests to rule out inflammatory or cancerous causes. These patients are classified as suffering from irritable bowel syndrome (IBS). Patients who have diagnosable inflammatory bowel disease (IBD) where colonoscopy is positive may suffer similar symptoms but also have no treatment for this type of symptom. It is becoming apparent that a large subgroup of IBS patients have undergone prior infection or inflammation, and that there are in fact changes in the types of cells in biopsies from their gut. Thus there are common features to IBS and inflammation. These may provide a means for us to find new treatments for IBS and IBD symptoms. Mice develop similar microscopic changes in the colon after experimental inflammation to those seen in humans, so we can discover more from this model. We have recently established that there are several types of sensory nerve fibres from the mouse colon and rectum that convey information about contractions, distension and chemical mediators released from tissue to the central nervous system. These are almost certainly responsible for generating symptoms in patients. We aim in this project to discover how these sensory nerves change in their responsiveness to mechanical and chemical stimuli in experimental inflammation. Importantly we shall investigate the mediators that are present in the tissue which may activate sensory nerves and-or the receptors on sensory nerves that may be increased. These experiments we hope will provide a target at which to aim novel drug treatments for symptoms of IBS and IBD.Read moreRead less
Molecular mechanisms of catalysis and the basis of substrate specificity in polysaccharide hydrolases. Reaction intermediates along hydrolytic pathways and molecular determinants of substrate specificity of barley B-glucan exo- and endohydrolases will be defined using crystallographic and kinetic analyses. These enzymes are of central importance in cell wall metabolism during development of higher plants, and in plant-pathogen interactions. Realization of the project objectives will not only pro ....Molecular mechanisms of catalysis and the basis of substrate specificity in polysaccharide hydrolases. Reaction intermediates along hydrolytic pathways and molecular determinants of substrate specificity of barley B-glucan exo- and endohydrolases will be defined using crystallographic and kinetic analyses. These enzymes are of central importance in cell wall metabolism during development of higher plants, and in plant-pathogen interactions. Realization of the project objectives will not only provide fundamental information on catalytic mechanisms, but will also provide opportunities to manipulate enzyme specificity. Further, site-directed mutagenesis of the enzymes will be used to generate glycosynthases, which will be evaluated for their ability to synthesise novel oligosaccharide and polysaccharide products, some of which might show immunomodulating activity.Read moreRead less
Polysaccharide Synthase Genes in Agro-Industrial Applications. Achievement of the project aims will generate valuable intellectual property and meet National Research Priorities by: enhancing our knowledge base for the production of renewable bio-fuels from crop residues, for an environmentally sustainable Australia; developing preventative healthcare through adoption of healthier diets, rich in non-starchy cell wall polysaccharides that help reduce the incidence and severity of cardiovascular d ....Polysaccharide Synthase Genes in Agro-Industrial Applications. Achievement of the project aims will generate valuable intellectual property and meet National Research Priorities by: enhancing our knowledge base for the production of renewable bio-fuels from crop residues, for an environmentally sustainable Australia; developing preventative healthcare through adoption of healthier diets, rich in non-starchy cell wall polysaccharides that help reduce the incidence and severity of cardiovascular disease, obesity, diabetes and some cancers; and by developing breakthrough science in emerging agricultural technologies. The alliance will foster an intellectual environment to provide world-class basic research outcomes and training of highly skilled graduates, thereby contributing to the 'knowledge nation'.Read moreRead less
Disruptive approaches to biological sensing. Optical fibre-based biosensors have the potential to transform our ability to monitor our environment, protect our nation's assets and safeguard our citizens, and to offer improved clinical diagnostics and food quality control by creating tools that can detect biomolecules in real-time within complex samples. To fulfil this mission, we propose to develop new fibre-based sensing architectures for sensing biomolecules that have the potential to be sensi ....Disruptive approaches to biological sensing. Optical fibre-based biosensors have the potential to transform our ability to monitor our environment, protect our nation's assets and safeguard our citizens, and to offer improved clinical diagnostics and food quality control by creating tools that can detect biomolecules in real-time within complex samples. To fulfil this mission, we propose to develop new fibre-based sensing architectures for sensing biomolecules that have the potential to be sensitive, selective, fast and compact.Read moreRead less
Regulation of Cellulose Biosynthesis in Commercially Important Cereal Crop Species. The long term strategic research alliance with DuPont Pioneer will lead to the development of breakthrough science in emerging technologies that are relevant: a) to agricultural production, b) to human health and c) to renewable bio-fuel production from crop residues. The alliance will attract significant international investment in Australian research and foster an intellectual environment for world-class resear ....Regulation of Cellulose Biosynthesis in Commercially Important Cereal Crop Species. The long term strategic research alliance with DuPont Pioneer will lead to the development of breakthrough science in emerging technologies that are relevant: a) to agricultural production, b) to human health and c) to renewable bio-fuel production from crop residues. The alliance will attract significant international investment in Australian research and foster an intellectual environment for world-class research training of postgraduate students and postdoctoral scientists, in both a higher education and an industry context.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120102821
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Molecular genetic adaptive processes in natural co-evolution between rabbits and the rabbit haemorrhagic disease virus. This project will use extensive sampling and long-term field data to reveal ongoing co-evolutionary mechanisms behind the increasing resistance of pest Australian wild rabbits against a viral pathogen. The results will increase the understanding of evolutionary mechanisms in nature and will provide basic information for biological pest control of rabbits.
The molecular interactome and functions of circular RNAs. This project aims to identify the functions of circular RNAs, the most contemporary and enigmatic family of RNA molecules. While their abundance suggests they are important, it is unclear how they function at the molecular level. This project aims to delineate circular RNA function by systematically identifying their interacting partners at the DNA, RNA and protein levels, the so-called molecular interactome. This project will reprogram e ....The molecular interactome and functions of circular RNAs. This project aims to identify the functions of circular RNAs, the most contemporary and enigmatic family of RNA molecules. While their abundance suggests they are important, it is unclear how they function at the molecular level. This project aims to delineate circular RNA function by systematically identifying their interacting partners at the DNA, RNA and protein levels, the so-called molecular interactome. This project will reprogram embryonic stem cells to model developmental processes and is designed to validate circular RNA research. Together, the benefits include a higher-quality research workforce by mentoring students, refining fundamental tenets of RNA biology and may extend to improving health in the long-term.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120100390
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Characterisation of collagenous lectins and their roles in ovine infectious diseases. Specific proteins involved in immunity against infections will be studied in sheep to enhance their immune response against specific infections, such as ovine Johne's disease and footrot. This may lead to selective breeding of sheep that are more resistant to disease, minimising production losses and use of medications.