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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
E-Cadherin Endocytosis In Morphogenesis: Recycling And Growth Factor Induced Uptake.
Funder
National Health and Medical Research Council
Funding Amount
$498,088.00
Summary
E-cadherin is a cell-cell adhesion protein expressed in all epithelia with essential roles in establishing cell polarity and in tissue patterning during development. In the adult, E-cadherin functions to maintain epithelial integrity. E-cadherin is also a vital tumour suppressor, protecting cells against metastatic transformation. Our earlier studies showed that E-cadherin is constantly moved, or trafficked, to and from the surface of epithelial cells. The endocytosis or internalisation of cell ....E-cadherin is a cell-cell adhesion protein expressed in all epithelia with essential roles in establishing cell polarity and in tissue patterning during development. In the adult, E-cadherin functions to maintain epithelial integrity. E-cadherin is also a vital tumour suppressor, protecting cells against metastatic transformation. Our earlier studies showed that E-cadherin is constantly moved, or trafficked, to and from the surface of epithelial cells. The endocytosis or internalisation of cell surface E-cadherin serves to regulate its role in adhesion. More recently, we and others have shown that E-cadherin is endocytosed in response to growth factors, in conjunction with the activated growth factor receptors themselves. E-cadherin can influence the trafficking and signaling of these receptor tyrosine kinases. This joint endocytosis is an elegant mechanism for the simultaneous downregulation of cell adhesion and activation of signaling for cell growth and motility. The growth and differentiation of epithelial cells during tissue patterning or morphogenesis relies critically on these endocytic pathways. Our research is aimed at defining the endosomes and cellular machinery involved in E-cadherin-receptor endocytosis, moreover we will pursue initial findings suggesting that there are different pathways and fates for E-cadherin endocytosed at the behest of different growth factors. We will study endocytosis during the processes of epithelial cyst formation and tubulation of cysts as an in vitro model for mammalian morphogenesis. These studies will provide important and novel information for understanding the roles of E-cadherin in adhesion and in growth factor signaling during epithelial morphogenesis. Ultimately these findings will be of relevance to epithelial development and the prevention of cancer.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE210101102
Funder
Australian Research Council
Funding Amount
$404,748.00
Summary
Single-Atom Catalysts on Atomically Thin Nanomaterials for H2O2 Production. Single-atomic sites supported on graphene analogs is an ideal structural mode for the design of electrocatalysts due to its ultimate small size limit, atomic thickness, and easily tuned electronic properties. This project aims to use a theory-guided approach to develop efficient electrocatalysts for the production of value-added hydrogen peroxide. The structural advantages of graphene analogs will be fully utilised to un ....Single-Atom Catalysts on Atomically Thin Nanomaterials for H2O2 Production. Single-atomic sites supported on graphene analogs is an ideal structural mode for the design of electrocatalysts due to its ultimate small size limit, atomic thickness, and easily tuned electronic properties. This project aims to use a theory-guided approach to develop efficient electrocatalysts for the production of value-added hydrogen peroxide. The structural advantages of graphene analogs will be fully utilised to unlock the catalytic power of single-atomic sites, and consequently achieve high catalytic activity and selectivity. The outcome will set a solid scientific foundation to enable economically viable technologies for eco-friendly hydrogen peroxide production and bring significant socioeconomic benefits to Australia.Read moreRead less
Atomically Thin 3d Transition Metal Electrocatalysts for Water Splitting. The current industrial-scale hydrogen productions are reliant on high temperature steam reforming fossil fuels, consuming large quantity of energy and fossil resources, and emitting huge amounts of CO2. This project aims to develop cheap and plentiful transition metal-based high performance water splitting electrocatalysts, enabling economically viable large-scale water electrolytic hydrogen production driven by renewable ....Atomically Thin 3d Transition Metal Electrocatalysts for Water Splitting. The current industrial-scale hydrogen productions are reliant on high temperature steam reforming fossil fuels, consuming large quantity of energy and fossil resources, and emitting huge amounts of CO2. This project aims to develop cheap and plentiful transition metal-based high performance water splitting electrocatalysts, enabling economically viable large-scale water electrolytic hydrogen production driven by renewable electricity. A theory-guided catalyst approach will be used to guide the efficient design and development of high performance electrocatalysts. The success of the project will lead to a suit of high performance water splitting electrocatalysts, leaping forward water electrolytic hydrogen production technology.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
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