A microfluidic approach to study the mechanobiology of ageing blood vessels. This project aims to study the effect of the stiffening of ageing arteries in endothelial cells. It explores the changes that occur in endothelial cells using a unique microfluidic technology with tuneable wall stiffness to mimic the biophysical and biochemical properties of ageing arteries. The expected outcome is the identification of the cellular mechanisms that control endothelial responses to arterial stiffening. T ....A microfluidic approach to study the mechanobiology of ageing blood vessels. This project aims to study the effect of the stiffening of ageing arteries in endothelial cells. It explores the changes that occur in endothelial cells using a unique microfluidic technology with tuneable wall stiffness to mimic the biophysical and biochemical properties of ageing arteries. The expected outcome is the identification of the cellular mechanisms that control endothelial responses to arterial stiffening. This should provide the fundamental knowledge required to assist in the development of new therapies to tackle age-related conditions such as cardiovascular disease and dementia.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE150101777
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Understanding the role of exosomes in intercellular communication. Exosomes, small packages released by cells, are powerful signalling organelles that can activate neighbouring cells by transferring proteins and RNA. Currently, it is unknown whether exosomes have similar membrane protein/lipid composition to that of the host cell. This project aims to explore the similarities and differences between the exosomal and host cell membranes in terms of the protein/lipid composition. In addition, the ....Understanding the role of exosomes in intercellular communication. Exosomes, small packages released by cells, are powerful signalling organelles that can activate neighbouring cells by transferring proteins and RNA. Currently, it is unknown whether exosomes have similar membrane protein/lipid composition to that of the host cell. This project aims to explore the similarities and differences between the exosomal and host cell membranes in terms of the protein/lipid composition. In addition, the project aims to study how the proteins and RNA are packaged into exosomes. Membrane molecules that are detected only in the exosomes may have important signalling implications and may aid in the uptake/fusion of exosomes by/with target cells. The project aims to improve our understanding on signalling mediated by exosomes.Read moreRead less
Characterisation of membrane protein ubiquitination by MARCH ligases. The goal of the project is to understand how a family of enzymes called MARCHs regulate expression and localisation of immunoregulatory receptors within cells by post-translational addition of a small protein tag called Ubiquitin. The aims are to decipher the ubiquitination patterns produced by the MARCHs; identify the E2 ligases used by the MARCHs to produce distinct Ub codes; and apply a new proteomic pipeline to identify no ....Characterisation of membrane protein ubiquitination by MARCH ligases. The goal of the project is to understand how a family of enzymes called MARCHs regulate expression and localisation of immunoregulatory receptors within cells by post-translational addition of a small protein tag called Ubiquitin. The aims are to decipher the ubiquitination patterns produced by the MARCHs; identify the E2 ligases used by the MARCHs to produce distinct Ub codes; and apply a new proteomic pipeline to identify novel representative MARCH substrates in mice deficient in six different MARCHs. It is anticipated the project will reveal novel insights into a fundamental cell biological process of major significance for regulation of protein expression and trafficking in cells of the immune system.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE150101648
Funder
Australian Research Council
Funding Amount
$363,000.00
Summary
A novel mechanism for the control of growth factor activity. Growth factors are secreted signalling molecules that govern fundamental biological processes such as cell growth, proliferation and death. The mechanism for growth factor control by a Membrane Attack Complex/Perforin-like (MACPF) protein is highly novel as MACPF proteins typically function to kill pathogens during the vertebrate immune response. This project aims to reveal how the MACPF protein Torso-like controls highly localised gro ....A novel mechanism for the control of growth factor activity. Growth factors are secreted signalling molecules that govern fundamental biological processes such as cell growth, proliferation and death. The mechanism for growth factor control by a Membrane Attack Complex/Perforin-like (MACPF) protein is highly novel as MACPF proteins typically function to kill pathogens during the vertebrate immune response. This project aims to reveal how the MACPF protein Torso-like controls highly localised growth factor signalling, using the sophisticated genetic and advanced imaging methods possible in the fruit fly Drosophila. This project aims to understand growth factor control as its deregulation leads to serious developmental disorders and diseases.Read moreRead less
Membrane trafficking and endosome to trans-Golgi network retrograde pathways. This project will study newly discovered and essential transport highways in cells, which connect the secretory and internalisation pathways. This research will enhance understandings of how molecules are transported along specific highways in cells. By training students, the project will contribute to the expertise of cell biology in Australia.
Phosphoinositide regulation of lysosome reformation during autophagy. This project aims to investigate a new critical step in the autophagy pathway, autophagic lysosome reformation, a fundamental, evolutionarily conserved mechanism for cellular homeostasis. By combining gene function studies with advanced cellular imaging techniques, this project will investigate the dynamic membrane changes that drive this lysosome recycling pathway and how it is regulated by a hierarchical succession of specif ....Phosphoinositide regulation of lysosome reformation during autophagy. This project aims to investigate a new critical step in the autophagy pathway, autophagic lysosome reformation, a fundamental, evolutionarily conserved mechanism for cellular homeostasis. By combining gene function studies with advanced cellular imaging techniques, this project will investigate the dynamic membrane changes that drive this lysosome recycling pathway and how it is regulated by a hierarchical succession of specific enzymes. The expected outcome will be to re-define the archetypical autophagy pathway and characterise novel mechanisms by which it is controlled. This project will reveal new fundamental biological processes, and act as a framework for developing new imaging modalities and tools for studying autophagy.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE170100575
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Pathogen detection in mammals. This project aims to study the role of a host molecule in immune protection. Multicellular organisms need to recognise pathogens to initiate immune protection. To do this, pathogen-specific molecules are presented to the immune system causing activation. Recently a mode of pathogen recognition was discovered in mammals. As microbes synthesise essential vitamins, they release tell-tale metabolite by-products, which a host molecule called MR1 captures and presents to ....Pathogen detection in mammals. This project aims to study the role of a host molecule in immune protection. Multicellular organisms need to recognise pathogens to initiate immune protection. To do this, pathogen-specific molecules are presented to the immune system causing activation. Recently a mode of pathogen recognition was discovered in mammals. As microbes synthesise essential vitamins, they release tell-tale metabolite by-products, which a host molecule called MR1 captures and presents to white blood cells. However, it is not understood how MR1 accomplishes this, the cellular machinery required, or how the metabolites are guided to MR1. Understanding this process is expected to explain microbial pathogen recognition.Read moreRead less
The molecular basis for efficacy at G protein coupled receptors. This project aims to investigate the molecular steps underlying the relationship between sensing by signal-transmitting proteins on the cell surface called G protein-coupled receptors and cellular response. The project aims to build on studies that have sought to understand the primary, molecular basis for this cellular volume control. This project seeks to use these novel approaches to fill this knowledge gap, providing a deeper u ....The molecular basis for efficacy at G protein coupled receptors. This project aims to investigate the molecular steps underlying the relationship between sensing by signal-transmitting proteins on the cell surface called G protein-coupled receptors and cellular response. The project aims to build on studies that have sought to understand the primary, molecular basis for this cellular volume control. This project seeks to use these novel approaches to fill this knowledge gap, providing a deeper understanding of how physiology and medicines work. The project expects to expand fundamental understanding of signal transmission at this receptor class. This project will deliver benefits including expanded basic knowledge and a contribution to future improvements in drug development.Read moreRead less
Plasmonic nanoparticles for probing and perturbing the spatial organisation of membrane proteins. Receptors on the surface of cells provide vital functions and represent a large fraction of drug targets. It is believed that the spatial organisation of receptors can effect their function. This project will test this hypothesis by combining nanotechnology with biophysics to watch and manipulate the spatial organisation of receptors.
A mechanism for pathogen detection highly conserved in mammals. This project aims to delineate biochemically how mammals fight pathogens by alerting their immune system to Vitamin B compounds produced by certain bacteria and fungi. The protein MR1 binds the compounds and displays them on the cell surface, activating pathogen-fighting MAIT cells. The MR1-MAIT cell axis is highly conserved in mammals and is thought to defend the host. This project expects to lead to new products to improve veterin ....A mechanism for pathogen detection highly conserved in mammals. This project aims to delineate biochemically how mammals fight pathogens by alerting their immune system to Vitamin B compounds produced by certain bacteria and fungi. The protein MR1 binds the compounds and displays them on the cell surface, activating pathogen-fighting MAIT cells. The MR1-MAIT cell axis is highly conserved in mammals and is thought to defend the host. This project expects to lead to new products to improve veterinary and human health services with new technology developed throughout the project and high-level training which will increase the competitiveness of the strategic biotechnology sector in Australia.Read moreRead less