Characterising Novel Alternative Splicing Networks That Promote Tumour Cell Plasticity
Funder
National Health and Medical Research Council
Funding Amount
$609,329.00
Summary
During cancer progression, tumour cells can change their properties and become more aggressive and resistant to therapies. We have identified an important regulator of this tumour cell transition, called “Quaking”, which causes widespread changes in gene splicing. We aim to investigate how "Quaking" causes changes in gene splicing and what the effects of these splicing changes are in tumour cells.
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
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
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
Improved methods for quantitation of acute phase proteins in biological samples. Using monoclonal antibodies and fluorescence polarisation, we aim to develop improved quantitative analytical methods that are superior to the current clinical assays. The initial targets will be C-reactive protein (CRP) and serum amyloid precursor protein (SAP), but the technology should be readily adaptable to other serum proteins. Better assays for CRP and SAP will greatly facilitate improved clinical management ....Improved methods for quantitation of acute phase proteins in biological samples. Using monoclonal antibodies and fluorescence polarisation, we aim to develop improved quantitative analytical methods that are superior to the current clinical assays. The initial targets will be C-reactive protein (CRP) and serum amyloid precursor protein (SAP), but the technology should be readily adaptable to other serum proteins. Better assays for CRP and SAP will greatly facilitate improved clinical management of those at risk of heart attack, the single biggest contributor to healthcare costs in Australia. We further aim to adapt this technology to enable "point-of-care" assays that would help medical practitioners, especially in rural areas, to make informed diagnoses immediately.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE210100604
Funder
Australian Research Council
Funding Amount
$436,600.00
Summary
How do cells sense and react to mechanical forces? There is accumulating evidence that mechanical forces exerted on tissues and cells strongly influences their behaviour. My research aims to understand how cells sense and respond to forces experienced throughout life. Using a combination of three-dimensional cell and tissue culture methods, I will investigate how compressive forces change the biochemistry of cells and their functionality. This work is aimed at generating fundamental knowledge to ....How do cells sense and react to mechanical forces? There is accumulating evidence that mechanical forces exerted on tissues and cells strongly influences their behaviour. My research aims to understand how cells sense and respond to forces experienced throughout life. Using a combination of three-dimensional cell and tissue culture methods, I will investigate how compressive forces change the biochemistry of cells and their functionality. This work is aimed at generating fundamental knowledge to improve our comprehension of how cells respond to force. The expected outcome is a greater understanding of mechanical and biochemical relationships between cells and the environment, to inform fields of tissue engineering of culture scaffolds to better mimic natural cell-tissue settings.Read moreRead less
Molecular mechanisms for seminal fluid signalling in reproduction. Male seminal fluid regulation of the female reproductive process influences fertility and fecundity in humans and animal species. Infertility and impaired reproductive function is a major economic constraint in livestock industries, and carries a substantial social and public health cost in humans. This research will identify the active signalling molecules in seminal fluid and quantify their importance in reproductive success ....Molecular mechanisms for seminal fluid signalling in reproduction. Male seminal fluid regulation of the female reproductive process influences fertility and fecundity in humans and animal species. Infertility and impaired reproductive function is a major economic constraint in livestock industries, and carries a substantial social and public health cost in humans. This research will identify the active signalling molecules in seminal fluid and quantify their importance in reproductive success and health of offspring. The outcomes will inform development of new diagnostic assays for male fertility, and underpin strategic design of novel fertility treatments and products with applications in the human health and animal breeding industries. Read moreRead less
The mechanochemical basis of cell polarity. This project aims to study how epithelial cells initiate polarisation, a major question in biology that conventional biochemical, cell biological and genetic approaches have not answered. This project will investigate the mechanochemical basis of symmetry breaking in the cellular cortex, a thin layer of actomyosin filaments underneath the plasma membrane, and how this forms signalling zones. Understanding polarity is expected to improve epithelia manip ....The mechanochemical basis of cell polarity. This project aims to study how epithelial cells initiate polarisation, a major question in biology that conventional biochemical, cell biological and genetic approaches have not answered. This project will investigate the mechanochemical basis of symmetry breaking in the cellular cortex, a thin layer of actomyosin filaments underneath the plasma membrane, and how this forms signalling zones. Understanding polarity is expected to improve epithelia manipulation in disciplines from tissue engineering to regenerative biology and reveal how epithelial architecture and physiology are generated.Read moreRead less