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
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
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
Understanding how cells regulate self eating during starvation and stress. This project aims to investigate how autophagosomes are built during autophagy by using advanced multi-modal imaging and unique gene-edited human cell lines. This project expects to generate new knowledge on how a family of evolutionary conserved proteins regulate autophagosome formation during starvation and stress conditions. Expected outcomes include the development of frontier imaging technologies that can be subseque ....Understanding how cells regulate self eating during starvation and stress. This project aims to investigate how autophagosomes are built during autophagy by using advanced multi-modal imaging and unique gene-edited human cell lines. This project expects to generate new knowledge on how a family of evolutionary conserved proteins regulate autophagosome formation during starvation and stress conditions. Expected outcomes include the development of frontier imaging technologies that can be subsequently utilised for the advancement of any field of cell biology. This should provide significant benefits by placing Australia at the forefront of cell biology technologies and increasing our understanding of how plant and human cells can protect themselves during starvation and stress.
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Mitochondrial biogenesis in mammalian cells. This project aims to understand the inner workings of a molecular machine involved in mitochondrial protein biogenesis. Mitochondria are essential organelles that provide the bulk of cellular energy. Genesis of the organelle relies on the coordinated synthesis and transport of both proteins and lipids that make up the organelle. This project plans to define the architecture of the molecular machine, outline how its components function, and explore the ....Mitochondrial biogenesis in mammalian cells. This project aims to understand the inner workings of a molecular machine involved in mitochondrial protein biogenesis. Mitochondria are essential organelles that provide the bulk of cellular energy. Genesis of the organelle relies on the coordinated synthesis and transport of both proteins and lipids that make up the organelle. This project plans to define the architecture of the molecular machine, outline how its components function, and explore the relationship between proteins and lipids in mitochondrial genesis. These results are expected to provide knowledge about how mitochondrial creation is regulated.Read moreRead less
The biogenesis of bacterial outer membranes; how bacteria build their surface membranes. The outer membrane protects probiotic bacteria in the human intestine and enables pathogenic bacteria to cause infectious diseases. We will determine bacteria build their outer membranes - outstanding training opportunities come through cutting edge technology and the development of skills not common in Australia.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100037
Funder
Australian Research Council
Funding Amount
$350,000.00
Summary
A cellular nano-imaging facility: Probing cellular complexity. Answering the major medical and biotechnology questions of the 21st century will be heavily reliant on the use of advanced imaging techniques. This facility will establish a new and revolutionary microscope which is capable of producing images of living cells in action at high magnification and with the greatest clarity.