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
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.
The glomerulus is the filtering component of the kidney. In many diseases, it can be the target of an inappropriate inflammatory response. As part of this response, white blood cells accumulate in the glomerulus where they cause damage. The aim of the project is to determine how these white blood cells accumulate in the glomerulus, specifically asking the question, what molecules present on the white blood cells and the glomerular blood vessels are required for this accumulation?
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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0347970
Funder
Australian Research Council
Funding Amount
$186,000.00
Summary
Integrated Bio-nano-fabrication Facility. The project proposes the upgrade of a joint facility for the probing, fabrication and operation of hybrid bio-nano-devices. The facility will enhance the proposers' capabilities in the area of the fundamental and prototype-type research on biomolecular/cellular devices. The ultimate goal of these projects is to thrust Australian science in the era when the essential functions of cells can be replicated and controlled on devices that are smaller than livi ....Integrated Bio-nano-fabrication Facility. The project proposes the upgrade of a joint facility for the probing, fabrication and operation of hybrid bio-nano-devices. The facility will enhance the proposers' capabilities in the area of the fundamental and prototype-type research on biomolecular/cellular devices. The ultimate goal of these projects is to thrust Australian science in the era when the essential functions of cells can be replicated and controlled on devices that are smaller than living cells. The proposed facility has a modular structure consisting of additional nano-positioning, confocal microscope and zeta potential modules built on the existent laser tweezers/scissors, picoliter pipette and Atomic Force Microscope modules.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
Surface Chemistry meets Cell Biology: Molecular Level Control of Surface Architecture for Cell Adhesion and Migration. Biotechnological applications such as tissue engineering, bone supports, implantable materials, cell assays and biosensors all require detailed knowledge of how cells interact with their environment. The proposed research aims to provide this knowledge by developing unique modified surfaces to investigate white blood cell migration and adhesion. Additional expected outcome will ....Surface Chemistry meets Cell Biology: Molecular Level Control of Surface Architecture for Cell Adhesion and Migration. Biotechnological applications such as tissue engineering, bone supports, implantable materials, cell assays and biosensors all require detailed knowledge of how cells interact with their environment. The proposed research aims to provide this knowledge by developing unique modified surfaces to investigate white blood cell migration and adhesion. Additional expected outcome will contribute to our understanding of the many fundamental cellular processes such as cell growth, differentiation and cell death as well as the molecular basis of diseases such as inflammation, cancer, cardiovascular diseases and wound healing. This research program will establish Australia as a leading force in this new research field.Read moreRead less
The development of tuneable materials to allow the three-dimensional printing of cells. New low cost three-dimensional (3D) printers and reagents will be developed during this project to allow cancer biologists to print cells and polymers as more realistic 3D tissue models for biological assays. Such technology will be important for performing basic research into cancers as well as for providing better tools for drug testing.
Dynamic Force Microscopy of small molecular assemblies. The possibility of manipulating a single molecule seems at first unreal, indeed 5 years ago it was pure science fiction. Through the gaining popularity of the Atomic Force Microscope (AFM) many perspectives about the molecular world are changing. Macroscopic effects such as adhesion and lubrication are now discussed in light of measurements made with this instrument. Newer work includes the observation of single protein unfolding experim ....Dynamic Force Microscopy of small molecular assemblies. The possibility of manipulating a single molecule seems at first unreal, indeed 5 years ago it was pure science fiction. Through the gaining popularity of the Atomic Force Microscope (AFM) many perspectives about the molecular world are changing. Macroscopic effects such as adhesion and lubrication are now discussed in light of measurements made with this instrument. Newer work includes the observation of single protein unfolding experiments. The biophysics oriented project detailed in this application will extend the AFM: into multi-molecular systems formed by self-assembly, such as cell membranes; into polyelectrolyte-surface interactions; and, finally into the sequencing of DNA.Read moreRead less