Recycling Of E-cadherin: Implications For Dynamic Cell Adhesion
Funder
National Health and Medical Research Council
Funding Amount
$250,494.00
Summary
E-cadherin is one of the major proteins responsible for mediating cell-to-cell adhesion in the body. During embryonic development E-cadherin is essential for establishing the normal body pattern and the cellular architecture of many epithelial organs. Throughout life E-cadherin serves to maintain epithelial barriers, such as the lining of the digestive tract. E-cadherin has been clearly identified as a tumour suppressor molecule: loss of normal E-cadherin function leads to tumour metastasis and ....E-cadherin is one of the major proteins responsible for mediating cell-to-cell adhesion in the body. During embryonic development E-cadherin is essential for establishing the normal body pattern and the cellular architecture of many epithelial organs. Throughout life E-cadherin serves to maintain epithelial barriers, such as the lining of the digestive tract. E-cadherin has been clearly identified as a tumour suppressor molecule: loss of normal E-cadherin function leads to tumour metastasis and cancer invasion. It is therefore essential to understand the physiological function and regulation of E-cadherin in cells. E-cadherin is normally expressed on the surface of cells for adhesion to neighbouring cells. Recently, we found that cells can internalise and recycle this surface E-cadherin: even in mature epithelia, a proportion of the E-cadherin molecules appear to undergo constant movement in and out of the cell. It is likely that this mechanism participates in the dynamic remodelling of adhesive contacts between cells in organs such as the gastrointestinal tract and during wound healing. Corruption of this recycling mechanism could also potentially contribute to tumorigenesis. In this grant we propose to build upon this discovery by investigating molecular and cellular mechanisms that mediate E-cadherin recycling. We will characterize the cellular pathways by which E-cadherin is trafficked. The signaling pathways that regulate recycling will be analysed, since these may be perturbed in cancer and inflammation. Other molecules that interact with E-cadherin will be studied to determine whether they too recycle. The information from these studies will have broad implications for understanding the role of E-cadherin in healthy organs and in common cancers.Read moreRead less
Manipulation Of Clathrin-mediated Trafficking By Coxiella
Funder
National Health and Medical Research Council
Funding Amount
$667,857.00
Summary
This research will uncover how Coxiella causes the serious infectious disease Q fever by commandeering human cells and replicating to high numbers within a specialised vacuole. We will investigate virulence factors of Coxiella, learning how and why they target an essential human vesicular trafficking process. Our innovative approach and unique expertise will elucidate interaction between this pathogen and the human cell, providing fundamental knowledge towards public health outcomes.
New biocompatible titanium alloys for next-generation metallic biomaterials. This project aims to develop a new class of titanium alloy biomaterials with enhanced mechanical compatibility, biocompatibility, and bio-functionality. The project expects to generate new knowledge in phase transformation mechanisms and advanced surface modification techniques for these alloys. Expected outcomes also include developments in phase transformation theories that enable high yield strength and low Young's m ....New biocompatible titanium alloys for next-generation metallic biomaterials. This project aims to develop a new class of titanium alloy biomaterials with enhanced mechanical compatibility, biocompatibility, and bio-functionality. The project expects to generate new knowledge in phase transformation mechanisms and advanced surface modification techniques for these alloys. Expected outcomes also include developments in phase transformation theories that enable high yield strength and low Young's modulus, and innovations in manufacturing techniques for new titanium alloys. This project will provide significant benefits to both Australian healthcare providers and bone-implant recipients through greater implant lifespans, improved patient outcomes and valuable savings to the healthcare system.Read moreRead less
Investigation Of The Molecular Mechanisms Underlying Alpha Synuclein Function At The Presynapse
Funder
National Health and Medical Research Council
Funding Amount
$419,180.00
Summary
Parkinson’s Disease (PD) is a common brain disease affecting 7 million people worldwide. It is caused by the death of brain cells. ?-synuclein is a protein in that brain that is likely to contribute to the cell death in PD, but the normal role of the protein remains unknown. This study will investigate the function of ?-synuclein in maintaining normal healthy brain activity. In addition, this work will help us understand how normal brain processes are affected in diseases such as PD.
Biocompatible magnesium alloys with specific materials properties. This project aims to develop biocompatible magnesium alloys with highly desirable mechanical properties and degradation on demand, and the fundamental science to achieve the materials properties. Injured human bones often need biomaterials to restore function. This project’s magnesium biomaterials could change the biomaterials field by making implant removal surgery unnecessary, and avoiding the adverse tissue reactions and stres ....Biocompatible magnesium alloys with specific materials properties. This project aims to develop biocompatible magnesium alloys with highly desirable mechanical properties and degradation on demand, and the fundamental science to achieve the materials properties. Injured human bones often need biomaterials to restore function. This project’s magnesium biomaterials could change the biomaterials field by making implant removal surgery unnecessary, and avoiding the adverse tissue reactions and stress shielding typically associated with conventional implanting metals. The outcomes are expected to provide insights in designing biodegradable magnesium alloys and surface coating technology, and generate intellectual properties and advanced biomaterials that will benefit the Australian ageing population.Read moreRead less
Regulation Of Synaptic Vesicle Biogenesis For Synaptic Transmission
Funder
National Health and Medical Research Council
Funding Amount
$339,115.00
Summary
The overall aim is to better understand the molecular processes of nerve cell communication during learning, memory and abnormal brain activity that cause neurological diseases. The supply and generation (biogenesis) of synaptic vesicles (SVs) in nerve cells is critical to sustain neurotransmission. It requires complex protein interactions and signalling. Thus modulation of SV biogenesis at the molecular level will allows future development of new targeted treatments for neurological diseases.
Molecular Mechanisms Of Mitotic Progression And The Anti-cancer Properties Of Anti-mitotic Agents
Funder
National Health and Medical Research Council
Funding Amount
$466,492.00
Summary
Mitosis is the final stage of the cell division cycle that produces two daughter cells. Incorrect localisation and modification of proteins that regulate this process cause cell division errors potentially leading to cancer. This project will characterise how key mitotic proteins co-operatively function to complete this process. This research will increase our understanding of the cell division errors that contribute to cancer development, ultimately identifying new targets for cancer therapy.
Designed to last: novel gradient coatings for extreme environments. Hard coatings are frequently applied to equipment operating in harsh environments. Often such coatings are highly brittle and so fragile under stress, especially at high temperatures or in corrosive environments. Premature failure can affect safety and lead to negative economic and environmental consequences. The objective of this project is to combine bioinspired microstructural design with an emerging alloying concept to produ ....Designed to last: novel gradient coatings for extreme environments. Hard coatings are frequently applied to equipment operating in harsh environments. Often such coatings are highly brittle and so fragile under stress, especially at high temperatures or in corrosive environments. Premature failure can affect safety and lead to negative economic and environmental consequences. The objective of this project is to combine bioinspired microstructural design with an emerging alloying concept to produce a breakthrough in the development of engineering coatings; for example, overcoming the long standing trade-off between hardness and toughness. Such an innovative coating is expected to be highly durable in extreme conditions, and in so doing will help transform manufacturing, mining and desalination industries.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE210101773
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Ultra-tough coatings via materials engineering . This project aims to develop new generation coatings that combine highly controlled compositions and bio-inspired microstructural characteristics for safety-critical applications. This is made possible through smart materials design, multi-scale modelling and novel fabrication technique. The new coatings are expected to offer exceptionally high toughness underlain by a unique combination of various strengthening modes at multiple length scales. Th ....Ultra-tough coatings via materials engineering . This project aims to develop new generation coatings that combine highly controlled compositions and bio-inspired microstructural characteristics for safety-critical applications. This is made possible through smart materials design, multi-scale modelling and novel fabrication technique. The new coatings are expected to offer exceptionally high toughness underlain by a unique combination of various strengthening modes at multiple length scales. The application of the coatings will enhance the performance and safety of mechanical components in engineering applications, reduce associated costs. In doing so, this project will bring substantial benefits to advanced manufacturing, mining and aerospace sectors. Read moreRead less