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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE130100136
Funder
Australian Research Council
Funding Amount
$340,000.00
Summary
Mobile weather radar system for advanced environmental monitoring and modelling. High spatial and temporal resolution weather radar data on wind and precipitation will translate to significant environmental model advances. Australian researchers will undertake model validation studies on precipitation, dust storm, and flood prediction under a wider range of environmental conditions and in greater detail than currently possible.
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
Discovery Early Career Researcher Award - Grant ID: DE150101297
Funder
Australian Research Council
Funding Amount
$320,094.00
Summary
Rethinking Australian drought risk, its long-term variability and processes. Drought risk describes the likelihood that damage will result from exposure to drought. This project aims to fundamentally reshape how we define, characterise and understand drought risk in Australia. A framework for drought risk will be applied that includes the complete range of characteristics that modulate the impacts of drought, which are the frequency of recurrence, duration, severity, seasonality and spatial exte ....Rethinking Australian drought risk, its long-term variability and processes. Drought risk describes the likelihood that damage will result from exposure to drought. This project aims to fundamentally reshape how we define, characterise and understand drought risk in Australia. A framework for drought risk will be applied that includes the complete range of characteristics that modulate the impacts of drought, which are the frequency of recurrence, duration, severity, seasonality and spatial extent. Long-term changes in drought risk will be examined and the process-based climatic risk factors will be identified. Advancing knowledge on the nature and causes of the long-term changes in drought risk is crucial to improving risk management of drought in the agricultural and water resource sectors.Read moreRead less
Modulating Immune Responses By Targeting Dendritic Cells Using Dendritic Cell Specific Markers.
Funder
National Health and Medical Research Council
Funding Amount
$197,750.00
Summary
The ability to modulate immune responses would have major health benefits. Dendritic cells (DC) are key regulators of the immune system. Different types of DC possess different cell surface molecules and have differing regulatory functions. We have identified four novel DC surface molecules that can be used to target different types of DC. We aim to use antibodies against these molecules to either enhance the effectiveness of vaccines or to suppress autoimmune diseases.
Extracting energy from air: mechanism of a bacterial hydrogenase. The atmosphere has recently been shown to be a key source of energy for diverse soil bacteria. Bacteria use complex enzymes, namely Huc-type hydrogenases, to harvest atmospheric hydrogen directly from air to support growth and survival. However, little is known about how Huc functions within and outside cells. By synergising expertise in microbiology, biochemistry, and chemistry, we will resolve the mechanism, assembly, and integr ....Extracting energy from air: mechanism of a bacterial hydrogenase. The atmosphere has recently been shown to be a key source of energy for diverse soil bacteria. Bacteria use complex enzymes, namely Huc-type hydrogenases, to harvest atmospheric hydrogen directly from air to support growth and survival. However, little is known about how Huc functions within and outside cells. By synergising expertise in microbiology, biochemistry, and chemistry, we will resolve the mechanism, assembly, and integration of Huc, including the basis of its remarkably high affinity and oxygen insensitivity compared to previously studied hydrogenases. This project will enable biotechnological applications, as the first study of an enzyme that extracts energy from air, and has broad ecological and biogeochemical implications.Read moreRead less
Precipitation in shallow convection over the Southern Ocean. This project aims to quantify the amount of precipitation over the Southern Ocean and identify the key dynamical and microphysical processes that lead to its development. Large uncertainties exist in the frequency and intensity of precipitation, which limits the ability to model the coupled Southern Ocean climate system. Observations from the RV Investigator, an Australian marine research vessel, have revealed heavy precipitation event ....Precipitation in shallow convection over the Southern Ocean. This project aims to quantify the amount of precipitation over the Southern Ocean and identify the key dynamical and microphysical processes that lead to its development. Large uncertainties exist in the frequency and intensity of precipitation, which limits the ability to model the coupled Southern Ocean climate system. Observations from the RV Investigator, an Australian marine research vessel, have revealed heavy precipitation events within the shallow convection commonly found between fronts that have not been captured by either satellite observations or numerical models. This project will improve weather forecasts, including precipitation, and climate projections over the Southern Ocean and the adjoining Antarctic and the southern part of Australia.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120102645
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
The cause of the poleward shift of Earth's storm tracks and jet streams. Why do global climate models shift the atmospheric storm tracks and jet streams poleward in simulations of future climate? This project will determine the underlying causes of the most important circulation change that is projected to occur with increasing greenhouse gases, and will allow much more accurate regional climate projections.
The dynamics of subtropical anticyclones and the connection to drought, heatwaves and bushfires in southern Australia. The aim of the project is to understand the dynamics of anticyclones (high pressure systems) in the region of southern Australia. The study of anticyclones in the region is important because of their very strong connection to rainfall in the winter, and heatwaves and bushfires in the summer, and because so little work has been done on understanding what is the defining feature o ....The dynamics of subtropical anticyclones and the connection to drought, heatwaves and bushfires in southern Australia. The aim of the project is to understand the dynamics of anticyclones (high pressure systems) in the region of southern Australia. The study of anticyclones in the region is important because of their very strong connection to rainfall in the winter, and heatwaves and bushfires in the summer, and because so little work has been done on understanding what is the defining feature of the climate of southern Australia. Understanding what controls the location and strength of these features will go a long way to explaining how the climate of southern Australia will change in a warmer world.Read moreRead less