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
PrtFII, A Streptococcus Pyogenes Fibronectin Binding Protein, And Invasive Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$296,540.00
Summary
Our recent work revealed that, in the Aboriginal population, young age is a risk factor for severe invasive diseases caused by group A streptococcus. For group A streptococcus infection to occur, bacterial attachment is the first step. The bacterium attaches to host cells through interactions involving host fibronectin and the pathogen's fibronectin-binding proteins. We have found that streptococcal strains from severe disease cases are more likely to have the gene for PrtFII, a fibronectin bind ....Our recent work revealed that, in the Aboriginal population, young age is a risk factor for severe invasive diseases caused by group A streptococcus. For group A streptococcus infection to occur, bacterial attachment is the first step. The bacterium attaches to host cells through interactions involving host fibronectin and the pathogen's fibronectin-binding proteins. We have found that streptococcal strains from severe disease cases are more likely to have the gene for PrtFII, a fibronectin binding protein, than those from uncomplicated skin sores. In this application we propose to extend this observation and compare biochemical properties of PrtFII from strains belonging to the above two sets of collections. We hypothesise that PrtFII from invasive strains bind to fibronectin more tightly than the proteins from strains that cause uncomplicated infection. We also will test whether sera from invasive disease cases have lower titre of antibodies to the conserved region of PrtFII than sera from uncomplicated cases. A streptococcal vaccine by necessity has to be a multi-component vaccine to cover a wide spectrum of diseases and epidemiological differences. The study proposed here may provide a basis to argue whether or not to include PrtFII in such a multi-component vaccine.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668382
Funder
Australian Research Council
Funding Amount
$1,000,000.00
Summary
e-Research Infrastructure for the Molecular and Materials Structure Sciences. Understanding molecular and materials structure in atomic detail is vital to a knowledge-based economy and a healthy society. The development of smart materials, nanotechnological devices, hydrogen storage materials, molecular switches, magnets and sensors, for example, depends on knowledge of three-dimensional atomic structure. Cures for illnesses such as SARS, AIDS and Alzheimer's disease and understanding the aging ....e-Research Infrastructure for the Molecular and Materials Structure Sciences. Understanding molecular and materials structure in atomic detail is vital to a knowledge-based economy and a healthy society. The development of smart materials, nanotechnological devices, hydrogen storage materials, molecular switches, magnets and sensors, for example, depends on knowledge of three-dimensional atomic structure. Cures for illnesses such as SARS, AIDS and Alzheimer's disease and understanding the aging process depends on knowledge of biomolecular structure. The deployment and development of automation-enhanced remote access to structural instruments through the web will greatly enhance Australian structure-based research, and make this science accessible to the public. Read moreRead less
DEVELOPMENT OF A NOVEL BIOMATERIAL FOR BONE TISSUE ENGINEERING. Tissue engineering of bone is emerging as a viable therapy for treating large defects in load-bearing bone. We wish to develop methods for combining novel heparan sulphate molecules (known to deliver growth factors to cell surfaces and thereby cause changes in bone cell phenotype) with load-bearing, macro-porous, biodegradable mineral/polymer biomaterials. Through the study of release profiles, protein adsorption and cell responses ....DEVELOPMENT OF A NOVEL BIOMATERIAL FOR BONE TISSUE ENGINEERING. Tissue engineering of bone is emerging as a viable therapy for treating large defects in load-bearing bone. We wish to develop methods for combining novel heparan sulphate molecules (known to deliver growth factors to cell surfaces and thereby cause changes in bone cell phenotype) with load-bearing, macro-porous, biodegradable mineral/polymer biomaterials. Through the study of release profiles, protein adsorption and cell responses to these derivatised biomaterials, a novel approach to bone replacement materials can be developed.Read moreRead less
Developing a new class of RNA delivery vehicle using synthetic virology. This project aims to develop robust protein cages derived from the empty shells of viruses, or capsids, to protect and deliver sensitive cargo such as RNA in agricultural settings. It will do so by directed evolution of non-infectious capsids in the lab. This will uncover the molecular mechanisms underpinning the response of viruses to chemical and biological signals and create a new class of RNA delivery vehicle. This synt ....Developing a new class of RNA delivery vehicle using synthetic virology. This project aims to develop robust protein cages derived from the empty shells of viruses, or capsids, to protect and deliver sensitive cargo such as RNA in agricultural settings. It will do so by directed evolution of non-infectious capsids in the lab. This will uncover the molecular mechanisms underpinning the response of viruses to chemical and biological signals and create a new class of RNA delivery vehicle. This synthetic biology approach combines virology and protein engineering to establish a platform biotechnology for stable and effective delivery. The project expects to demonstrate the potential of nature’s nanoparticles, virus capsids, to enhance the efficacy of RNA technologies in a wide range of applications.Read moreRead less
Multiplexed Molecular Reading of Protein Associations via Nanoscaled Devices. Current developments in Nanoscience and Nanotechnology hold many promises in terms of revolutionising our industrial base, transforming biology, medical science and practice. This project strives to achieve some of these goals by, for the first time, building and testing nano-scaled devices with the capability to rapidly ?read? information about complex protein associations. With the recent completion of the Human Ge ....Multiplexed Molecular Reading of Protein Associations via Nanoscaled Devices. Current developments in Nanoscience and Nanotechnology hold many promises in terms of revolutionising our industrial base, transforming biology, medical science and practice. This project strives to achieve some of these goals by, for the first time, building and testing nano-scaled devices with the capability to rapidly ?read? information about complex protein associations. With the recent completion of the Human Genome project, major opportunities exist to provide spectacular advances in human health care (eg, via novel diagnostics) provided that appropriate high-throughput biological reading devices can be developed. In developing such devices, this project also aims to catalyse the Australian Nanotechnology/Biotechnology industry.Read moreRead less
Metals in biocatalysis. Metals and enzymes are essential for the chemistry of life. This project will aim to garner the potential of metal-dependent enzymes to develop new drugs against osteoporosis, combat the spread of antibiotics resistance and optimise some of these enzymes to detoxify pesticide-polluted environments, thus contributing to global health and food security.
Smart Nanocapsules for Efficient Cellular Delivery of Bioactive Peptide Drugs. This project will bring about practical benefits in terms of developing efficient therapeutic drug delivery systems, which has a market growth estimated to be ca. 23% p.a. in the world. The novel encapsulation technology developed in this project is not only desirable for biomolecules but also applicable for other functional materials and will find wide applications in a number of fields, such as chemical, food proces ....Smart Nanocapsules for Efficient Cellular Delivery of Bioactive Peptide Drugs. This project will bring about practical benefits in terms of developing efficient therapeutic drug delivery systems, which has a market growth estimated to be ca. 23% p.a. in the world. The novel encapsulation technology developed in this project is not only desirable for biomolecules but also applicable for other functional materials and will find wide applications in a number of fields, such as chemical, food processing and cosmetic industries. Successful completion of the project can also strengthen our capacity to participate in new areas of research and positioning Australia at the forefront of bionanotechnology.Read moreRead less
Carbon-based electrode materials for electrochemical energy storage and water desalination. Clean energy and water resource are two critical issues for an environmentally sustainable Australia. The research project will lead to the discovery of innovative carbon-based electrode materials with well-designed physical and chemical properties for clean energy storage and alternative water desalination technology.