KLK4 Is A Master Regulator Of Tumour Microenvironment Remodelling In Prostate Cancer And Bone Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$596,305.00
Summary
The current biomarker for prostate cancer, PSA, belongs to a large family of related proteins called KLK enzymes. We have evidence that one of these enzymes, KLK4, regulates many different pathways involved in tumour spreading especially to bones. This project will determine the specific components involved with a view to finding better biomarkers of tumour spread and bone metastasis and designing better treatments for these aspects of the disease.
Polarized Trafficking Of E-cadherin In Epithelial Cells.
Funder
National Health and Medical Research Council
Funding Amount
$515,564.00
Summary
The cell adhesion protein E-cadherin is expressed in all epithelial tissues of the body where it has essential functions during development and in the adult in establishing and maintaining polarized cell monolayers. E-cadherin is also a vital tumour suppressor, its normal function guarantees that cells or even early tumours cannot metastasise; in contrast E-cadherin is always lost or malfunctions in malignant tumours. Earlier studies showed that E-cadherin is constantly moved, or trafficked, to ....The cell adhesion protein E-cadherin is expressed in all epithelial tissues of the body where it has essential functions during development and in the adult in establishing and maintaining polarized cell monolayers. E-cadherin is also a vital tumour suppressor, its normal function guarantees that cells or even early tumours cannot metastasise; in contrast E-cadherin is always lost or malfunctions in malignant tumours. Earlier studies showed that E-cadherin is constantly moved, or trafficked, to and from the surface of epithelial cells. This trafficking has dual roles, firstly in delivering newly-made E-cadherin to the surface where it functions and secondly, in regulating its adhesive function. Our research in this project is focussed on the molecules and intracellular compartments that control the delivery of E-cadherin to the cell surface. E-cadherin must be sorted in order to be delivered to the correct side of the cell. Having previously discovered the sorting signal in E-cadherin, we will now identify the cognate adaptor protein(s) that accomplish this sorting. New imaging techniques allow us to study protein trafficking inside live cells. Such studies have recently revealed that E-cadherin passes through a recycling endosome compartment on its way to the cell surface. This unexpected route, and the structure and role of the recycling endosome will now be studied in detail in live cells. Finally we will compare the sorting and trafficking of E-cadherin with the closely-related N-cadherin protein, to determine whether there are inherent differences in their trafficking that could explain their opposite roles in tumour cells, where N-cadherin is substituted for E-cadherin and allows metastatic behaviour. These studies will provide important information for understanding the adhesive and tumour suppressive roles of E-cadherin. In addition our findings will generate information fundamental to our understanding of cell polarity and protein sorting.Read moreRead less
Intervalence Transfer in Dinuclear and Oligonuclear Polymetallic Assemblies. Mixed-valence compounds (such as the pigment Prussian Blue) have been known for over two centuries, and possess important conductivity, magnetic and spectral properties. Electron transfer between the elements of different valency (intervalence charge transfer, IVCT) gives rise to absorbances in the red or near-infrared region of the spectrum which provide fundamental information on the electron migration. By design of ....Intervalence Transfer in Dinuclear and Oligonuclear Polymetallic Assemblies. Mixed-valence compounds (such as the pigment Prussian Blue) have been known for over two centuries, and possess important conductivity, magnetic and spectral properties. Electron transfer between the elements of different valency (intervalence charge transfer, IVCT) gives rise to absorbances in the red or near-infrared region of the spectrum which provide fundamental information on the electron migration. By design of target di- and higher nuclearity polymetallic species, the project will study IVCT phenomena to understand electron movement, allowing rational development of applicable materials such as catalysts, light-activated devices and non-linear optical materials.Read moreRead less
Pro-Fluorescent Aryl Nitroxides: New Probes for Polymer Lifetime and Kinetics Research. Internal aryl rings present in novel probes developed for this project impart fluorescence which is efficiently and internally quenched by the presence of a paramagnetic nitroxide group. Scavenging of radicals by the nitroxide however "switches on" the fluorescence and this enables powerful new fluorescence-based detection levels for the technique of nitroxide free radical scavenging. Such sensitivity is a ....Pro-Fluorescent Aryl Nitroxides: New Probes for Polymer Lifetime and Kinetics Research. Internal aryl rings present in novel probes developed for this project impart fluorescence which is efficiently and internally quenched by the presence of a paramagnetic nitroxide group. Scavenging of radicals by the nitroxide however "switches on" the fluorescence and this enables powerful new fluorescence-based detection levels for the technique of nitroxide free radical scavenging. Such sensitivity is applicable to polymerization kinetics studies, as well as providing new means for the determination of materials lifetimes. The development of pro-fluorescent markers as indicators for polymer degradation would be a significant outcome for materials where component failure has a major negative impact.Read moreRead less
Molecular archaeology: new knowledge from molecular weight distributions of synthetic and natural polymers. This project will lead to new understanding of how natural and synthetic polymers are formed. Examples are the enzymatic processes that produce the subtle architecture of rice grains, and the processes that pose problems for developing new techniques for making novel polymer-based materials. The fundamental scientific knowledge from this project will provide a platform for the future devel ....Molecular archaeology: new knowledge from molecular weight distributions of synthetic and natural polymers. This project will lead to new understanding of how natural and synthetic polymers are formed. Examples are the enzymatic processes that produce the subtle architecture of rice grains, and the processes that pose problems for developing new techniques for making novel polymer-based materials. The fundamental scientific knowledge from this project will provide a platform for the future development of improved materials, and for superior grain varieties for food and industrial use. These advances will be of significant benefit to Australian industry and consumers.Read moreRead less
Graft copolymers from starch and synthetic monomers. Polymer dispersions, manufactured as latexes in large quantities in Australia and elsewhere, have myriad applications, such as in adhesives, bitumen modifiers, paints and paper coatings. This project will create the enabling science to replace by starch the current synthetic products used to stop these dispersions from coagulating. This will create new uses for renewable resources and will reduce environmental insult by avoiding the leaching o ....Graft copolymers from starch and synthetic monomers. Polymer dispersions, manufactured as latexes in large quantities in Australia and elsewhere, have myriad applications, such as in adhesives, bitumen modifiers, paints and paper coatings. This project will create the enabling science to replace by starch the current synthetic products used to stop these dispersions from coagulating. This will create new uses for renewable resources and will reduce environmental insult by avoiding the leaching of biologically incompatible chemicals. By using starch from crops suited for Australia's arid climate, the new technology will reduce both our dependence on imported products and our greenhouse gas emissions.Read moreRead less
Synthesis of nanocomposite polymers with targeted properties. This project aims to synthesise novel nanocomposite polymers by living radical polymerisation in water and to understand the way polymer microstructure and nanomorphology control material properties. This will provide the enabling science so that nanomaterials with targeted properties can be tailor-made for biomedical and speciality-coatings applications, and thus dispense with the current trial-and-error methodology. The innovations ....Synthesis of nanocomposite polymers with targeted properties. This project aims to synthesise novel nanocomposite polymers by living radical polymerisation in water and to understand the way polymer microstructure and nanomorphology control material properties. This will provide the enabling science so that nanomaterials with targeted properties can be tailor-made for biomedical and speciality-coatings applications, and thus dispense with the current trial-and-error methodology. The innovations in this project are the novel synthesis of complex polymer architectures in water, and the first quantitative and qualitative structure-property correlations for such materials. This will also result in a deepened understanding of the mechanisms governing the formation of these nanocomposites.Read moreRead less