Targeting MicroRNA-driven Mesenchymal To Epithelial Transition To Suppress Prostate Cancer Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$741,831.00
Summary
Prostate cancer kills ~3,000 men per year in Australia. The development of metastasis is the major cause of prostate cancer-associated death and has limited treatment options. In this study, we will characterise the role of a group of molecules, termed microRNAs, in prostate cancer metastasis. We will also test whether targeting microRNAs using novel drugs termed antagomiRs is an effective strategy to inhibit metastasis and thereby improve prostate cancer mortality.
MicroRNAs are small molecules that modulate the expression of most genes and so affect nearly every biological process and pathology although, they were only discovered in humans less than 10 years ago. The bottleneck in discovering the functions of miRNAs is in identifying their molecular targets, the majority of which remain unknown. We aim to comprehensively identify direct target genes of epithelial-specific microRNAs and to confirm a number of them by gene target validation approaches.
Role Of The MiR-200 Target Quaking In Alternative Splicing During EMT And Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$443,160.00
Summary
The spread of cancer to other organs involves cancer cells changing to a more aggressive state and is a major cause of cancer related death. MicroRNAs are a class of genes that control whether cancer cells become more aggressive by regulating other genes. In this project we will examine the function of a new microRNA target which controls the cancer cell aggression. The outcome will be a better understanding of how cancers spread and the identification of new therapeutic targets.
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
How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misf ....How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misfolded proteins during ageing, within the nervous system of a living animal. Expected outcomes of this project will generate new knowledge of brain physiology and ageing relevant to all animals. This should provide significant benefits, such as a greater understanding of long-term brain functions including memory.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
Glucose is a critical fuel for living organisms and its presence in the gut triggers nerves that slow stomach emptying. However, little is known of how glucose is actually detected in the gut. We have established that sweet taste molecules of the tongue are also present in the gut, where they may detect glucose. This research will measure the expression and function of these molecules in the gut of humans and mice, and reveal key information on their potential as targets in health and disease.
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