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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
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
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
The function of the ribbon structure of the Golgi apparatus in vertebrates. The aim of the project is to determine the function of the Golgi ribbon structure in higher order cell functions, including metabolism, cell cycle, and cell polarity in both cultured cells and whole organisms. Understanding of the functions of the Golgi has been restricted to the regulation of glycosylation and membrane transport. However, it is now recognised that the Golgi apparatus feeds into the wiring of a range of ....The function of the ribbon structure of the Golgi apparatus in vertebrates. The aim of the project is to determine the function of the Golgi ribbon structure in higher order cell functions, including metabolism, cell cycle, and cell polarity in both cultured cells and whole organisms. Understanding of the functions of the Golgi has been restricted to the regulation of glycosylation and membrane transport. However, it is now recognised that the Golgi apparatus feeds into the wiring of a range of cellular networks in higher organisms such as cell polarisation, directed migration, metabolism and autophagy. Vertebrates have evolved mechanisms for joining individual Golgi stacks into a ribbon structure. The relevance of this ribbon structure remains a mystery. The project aims to answer this major question in cell biology.Read moreRead less
The mechanism of pore formation by Membrane Attack Complex/Perforin-like proteins. Members of the Membrane Attack Complex / Perforin (MACPF) family of proteins are essential for life, playing fundamental roles in immunity, tissue development and neuron formation. This project seeks to understand the basic mechanism of how MACPF proteins can form pores in target cells, a process central for killing in mammalian immunity.
A structural investigation into T cell signalling machines. The project aims to understand how receptor recognition events cause intracellular signalling.Membrane-bound receptors, their cognate ligands and the ensuing intracellular activation signal determine cellular fate. The project will explore events central to cellular immunity by examining the T cell signalling machinery. This project will use labelling, crystallographic and cryo-electron microscopy studies, to determine the molecular arc ....A structural investigation into T cell signalling machines. The project aims to understand how receptor recognition events cause intracellular signalling.Membrane-bound receptors, their cognate ligands and the ensuing intracellular activation signal determine cellular fate. The project will explore events central to cellular immunity by examining the T cell signalling machinery. This project will use labelling, crystallographic and cryo-electron microscopy studies, to determine the molecular architecture of the T cell receptor (TCR) CD3 complex, a molecular machine central to T cell signalling. This project should reveal how antigen recognition leads to T cell signal transduction which will create jobs, bring substantial health benefits and improve quality of life for Australians.Read moreRead less
A novel regulator of growth signalling in Drosophila. This project aims to increase understanding of how growth is regulated by growth factor hormones. In animals, growth is controlled by signalling pathways that are activated by secreted peptide hormones. A new regulator of growth in the fruitfly Drosophila, the membrane attack complex/perforin-like (MACPF) protein Torso-like, has been identified. The project aims to unravel how Torso-like functions to regulate growth, thus throwing light on th ....A novel regulator of growth signalling in Drosophila. This project aims to increase understanding of how growth is regulated by growth factor hormones. In animals, growth is controlled by signalling pathways that are activated by secreted peptide hormones. A new regulator of growth in the fruitfly Drosophila, the membrane attack complex/perforin-like (MACPF) protein Torso-like, has been identified. The project aims to unravel how Torso-like functions to regulate growth, thus throwing light on the role this protein family may play in all animals. The findings are expected to provide key insights into the modification of growth factor activity, which is often dysregulated in human cancers and growth disorders, and may enable the design of new strategies for interfering with insect development for pest control.Read moreRead less
A structural and molecular investigation into the basic mechanism of T cell receptor complex function. Cellular fate is determined by interactions between membrane-bound receptors and their cognate ligands. The basic mechanism of how such receptor-mediated recognition events cause intracellular signalling is poorly understood in most biological systems, including the cellular immune recognition axis. This project will explore events central to cellular immunity by examining the interactions cent ....A structural and molecular investigation into the basic mechanism of T cell receptor complex function. Cellular fate is determined by interactions between membrane-bound receptors and their cognate ligands. The basic mechanism of how such receptor-mediated recognition events cause intracellular signalling is poorly understood in most biological systems, including the cellular immune recognition axis. This project will explore events central to cellular immunity by examining the interactions centred on T-cell receptor complexes. This project will explore the molecular mechanisms underpinning these key receptor-recognition events and relate these observations to T-cell activation. The proposal will shed fundamental insight into Major Histocompatibility Complex restriction, T-cell development and how antigen recognition leads to T-cell signal transduction. Read moreRead less