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
Cause and effect: new mechanisms of particles formation in thunderstorms. This project aims to identify meaningful and specific indicators for predicting particle formation and alteration during thunderstorms. How thunderstorms develop is well-understood. However, identifying meaningful and specific indicators for predicting particle alteration during a thunderstorm is still not clear. This project will practically contribute to the evidence of the impact of air particulates, thereby having dire ....Cause and effect: new mechanisms of particles formation in thunderstorms. This project aims to identify meaningful and specific indicators for predicting particle formation and alteration during thunderstorms. How thunderstorms develop is well-understood. However, identifying meaningful and specific indicators for predicting particle alteration during a thunderstorm is still not clear. This project will practically contribute to the evidence of the impact of air particulates, thereby having direct implications for meteorological, and air pollution policy in Australia and worldwide. This project will allow researchers to understand the impact of these factors on the escalation of the causative effects, and to find a way to prevent unnecessary fatal outcomes.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
The dynamics of turbulent entrainment in sheared convective boundary layers. This project aims to develop general laws to enable the accurate prediction of boundary layer entrainment processes. This will be significant in a wide range of environmental and engineering applications. In particular, the current lack of understanding of this area is a major source of uncertainty in the latest generation of global climate models.
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
ARC Centre of Excellence for Climate Extremes. This Centre aims to transform understanding of past and present climate extremes and revolutionise Australia’s capability to predict them into the future. Climate extremes cost Australia up to $4 billion a year and will intensify over coming decades. This Centre’s blue-sky research will discover processes that explain the behaviour of present and future climate extremes. It will use its researchers, data, modelling, collaboration, graduate programme ....ARC Centre of Excellence for Climate Extremes. This Centre aims to transform understanding of past and present climate extremes and revolutionise Australia’s capability to predict them into the future. Climate extremes cost Australia up to $4 billion a year and will intensify over coming decades. This Centre’s blue-sky research will discover processes that explain the behaviour of present and future climate extremes. It will use its researchers, data, modelling, collaboration, graduate programme and early career researcher mentoring to transform Australia’s capacity to predict climate extremes. This research is expected to make Australia more resilient to climate extremes and minimise risks from climate extremes to the Australian environment, society and economy.Read moreRead less
Reactivity and photochemistry of halide anions: atmospheric implications. Bromine and iodine are suspected to be responsible for most of the halogen-induced ozone loss in the stratosphere but are not currently included in atmospheric models due to a paucity of knowledge of the gas-phase chemistry and photochemistry of their anions and radicals. This project will develop and deploy advanced mass spectrometry and laser spectroscopy techniques to enable precision measurements of the reactions and p ....Reactivity and photochemistry of halide anions: atmospheric implications. Bromine and iodine are suspected to be responsible for most of the halogen-induced ozone loss in the stratosphere but are not currently included in atmospheric models due to a paucity of knowledge of the gas-phase chemistry and photochemistry of their anions and radicals. This project will develop and deploy advanced mass spectrometry and laser spectroscopy techniques to enable precision measurements of the reactions and photo-reactions of gas-phase iodide and bromide anions and their oxides. These state-of-the-art measurements of reaction kinetics and products will enable accurate chemical models that predict the impact of bromine and iodine chemistry on ozone levels and will inform future models for global climate.Read moreRead less
GBR as a significant source of climatically relevant aerosol particles. Every cloud drop is formed from a microscopic aerosol particle, known as a cloud condensation nuclei (CCN). In unpolluted environments the CCN particles originate from biogenic sources. Determining the magnitude and driving factors of biogenic aerosol production in different ecosystems is crucial to the development and improvement of climate models. This project aims to determine the mechanisms of new particle production fro ....GBR as a significant source of climatically relevant aerosol particles. Every cloud drop is formed from a microscopic aerosol particle, known as a cloud condensation nuclei (CCN). In unpolluted environments the CCN particles originate from biogenic sources. Determining the magnitude and driving factors of biogenic aerosol production in different ecosystems is crucial to the development and improvement of climate models. This project aims to determine the mechanisms of new particle production from one of the biggest ecosystems in Australia, the Great Barrier Reef. It is expected that the project will establish whether marine aerosol along the Queensland coast is coral-derived and show that this aerosol can affect the CCN concentration and therefore cloud formation and the hydrological cycle.Read moreRead less