The protein O-glycosylation pathway of Neisseria: a model system for O-glycosylation of bacterial proteins with potential use in biotechnology. Proteins can be modified by the addition of sugar molecules. This process, called glycosylation, has been studied for some time in humans and other higher organisms, but is relatively new in the field of bacteria. This study will use the bacterium Neisseria as a model system for this process and work to harness the system for use in biotechnology.
"Painting" the 3D proteome: folding, conformation and interactions. The project aims to develop a "residue painting approach", employing novel chemical biology reagents and advanced quantitative proteomics, to monitor changes in protein folding, conformations and interactions in cells, in response to stimuli. Proteins direct almost all functions required to sustain life. The project expects to map the dynamic 3D-structures of thousands of proteins that inform the networks they are in, and of the ...."Painting" the 3D proteome: folding, conformation and interactions. The project aims to develop a "residue painting approach", employing novel chemical biology reagents and advanced quantitative proteomics, to monitor changes in protein folding, conformations and interactions in cells, in response to stimuli. Proteins direct almost all functions required to sustain life. The project expects to map the dynamic 3D-structures of thousands of proteins that inform the networks they are in, and of the conformations they adopt. Expected outcomes include the development of novel biotechnology tools for protein structure and function analysis, the illumination of important cell biology pathways underpinning molecular responses to stimuli and stress, and the training of our next generation of scientists.Read moreRead less
Retromer directs membrane protein trafficking within the endosome. The exposure of proteins to the extracellular environment is dependent on how the travel through the various regions of the cell. The work will lead to a richer understanding of how this process is regulated by protein complexes. These complexes act within cells to drive the formation of membrane transport tubules containing cargo molecules.
Making muscle: molecular dissection of membrane domain formation. For a muscle to contract efficiently in response to an electrical signal it requires the formation of an extensive system of hollow membranous tubules through which the signal can be propagated. This proposal addresses the molecular mechanisms involved in the formation of this tubule system in skeletal muscle. This project will develop cell biology in a whole organism rather than a cell culture system and provide a new framework f ....Making muscle: molecular dissection of membrane domain formation. For a muscle to contract efficiently in response to an electrical signal it requires the formation of an extensive system of hollow membranous tubules through which the signal can be propagated. This proposal addresses the molecular mechanisms involved in the formation of this tubule system in skeletal muscle. This project will develop cell biology in a whole organism rather than a cell culture system and provide a new framework for Australian and international cell biologists. It will generate new knowledge, train young Australian scientists, help build international collaborative networks and engage the public outside the research community.Read moreRead less
The core inflammasome as a model for caspase activation. This project aims to change the paradigm for the structure of the active inflammasome. Inflammasomes activate caspases, enzymes central to cell death and inflammatory processes. The current concept of inflammasomes is that caspases are recruited into a single massive protein complex seen as a “speck” in the cell. This project proposes the speck is a terminal stage, after the major enzymatic activity is over. This project aims to purify sma ....The core inflammasome as a model for caspase activation. This project aims to change the paradigm for the structure of the active inflammasome. Inflammasomes activate caspases, enzymes central to cell death and inflammatory processes. The current concept of inflammasomes is that caspases are recruited into a single massive protein complex seen as a “speck” in the cell. This project proposes the speck is a terminal stage, after the major enzymatic activity is over. This project aims to purify smaller early stage inflammasome complexes, for structural analysis. The outcome will be a clearer understanding of processes of caspase activation and inflammasome formation. This will provide significant benefits, such as improve our understanding of processes of cell death and innate immunity, and train students.Read moreRead less
An integrated nano-bioengineered chip for enhanced molecular evolution. This project aims to develop a novel molecular evolution platform technology for the rapid selection of high value target binding molecules from diverse molecular libraries using an electrically activated nanofluidic chip coated with target. Significant outcomes from the project is the controlled selection of target binding molecules that is not possible with current methods and improved understanding of nanoforce driven mol ....An integrated nano-bioengineered chip for enhanced molecular evolution. This project aims to develop a novel molecular evolution platform technology for the rapid selection of high value target binding molecules from diverse molecular libraries using an electrically activated nanofluidic chip coated with target. Significant outcomes from the project is the controlled selection of target binding molecules that is not possible with current methods and improved understanding of nanoforce driven molecular collisions on nano-bioengineered surfaces. This provides significant benefits, creating new knowledge in nanomaterials and advanced manufacturing of nanofabricated devices, creating commercial interest and positioning Australia at the forefront of molecular discovery technology, a highly valuable global market.
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Moonlighting from sugar to metal. This project intends to use integrated genetics, biochemistry and omics to decipher the roles of the highly conserved OST3 proteins, which have been implicated in the disparate functions of regulating protein glycosylation and transporting magnesium. The project plans to detail the role of OST3 proteins in regulating mammalian glycosylation and reconstruct the vertebrate co-evolutionary trajectory of OST3 protein–substrate interactions. It also aims to identify ....Moonlighting from sugar to metal. This project intends to use integrated genetics, biochemistry and omics to decipher the roles of the highly conserved OST3 proteins, which have been implicated in the disparate functions of regulating protein glycosylation and transporting magnesium. The project plans to detail the role of OST3 proteins in regulating mammalian glycosylation and reconstruct the vertebrate co-evolutionary trajectory of OST3 protein–substrate interactions. It also aims to identify and characterise the regulation, mechanisms and metabolic consequences of OST3 protein-mediated magnesium transport. These outcomes may provide insights into eukaryotic biology, and allow advances in engineered systems for glycoprotein production and modulating cellular metabolism with potential research and therapeutic utility.Read moreRead less
Molecular networks underlying mitochondrial biogenesis in humans. Mitochondria are essential for life, and we propose a highly-innovative approach (employing multiple, cutting-edge ‘omic’ technologies and bioinformatics) to advance the fundamental understanding of how mitochondria respond and adapt to exercise in humans. The project outcomes should include significant new knowledge and advanced expertise that can be used by others to facilitate additional research outcomes. The project anticipa ....Molecular networks underlying mitochondrial biogenesis in humans. Mitochondria are essential for life, and we propose a highly-innovative approach (employing multiple, cutting-edge ‘omic’ technologies and bioinformatics) to advance the fundamental understanding of how mitochondria respond and adapt to exercise in humans. The project outcomes should include significant new knowledge and advanced expertise that can be used by others to facilitate additional research outcomes. The project anticipates the contribution of innovative tools for molecular biology research, benefiting therapeutic and biotechnology applications. This project will support advanced training of young researchers in frontier technologies, which will expand Australian research capabilities and help produce a higher quality workforce.Read moreRead less
A novel click chemistry approach to identify learning and memory molecules. This project seeks to contribute to a deeper understanding at a molecular level of how memory is stored in neurons. Long-term memories do not form immediately after learning. Initially fragile, they become resistant to disruption through a process known as memory consolidation. In a second process, termed reconsolidation, pre-established memories are updated and re-stored. Both processes depend on protein synthesis, but ....A novel click chemistry approach to identify learning and memory molecules. This project seeks to contribute to a deeper understanding at a molecular level of how memory is stored in neurons. Long-term memories do not form immediately after learning. Initially fragile, they become resistant to disruption through a process known as memory consolidation. In a second process, termed reconsolidation, pre-established memories are updated and re-stored. Both processes depend on protein synthesis, but little is known about the particular sets of proteins that are involved. The project plans to apply a novel biochemical protocol to a newly established transgenic mouse model that allows the visualisation and identification of newly synthesised proteins in the hippocampus, a brain area that is critical in memory formation.Read moreRead less
The endosome at atomic resolution. The project seeks to improve understanding of intracellular transport. The transport of proteins is essential for controlling the interactions of a cell with its environment, and for regulating a huge number of cell signalling events. The retromer protein complex is a central mediator of intracellular trafficking in organelles called endosomes. It is vital for normal cell homeostasis in all eukaryotic organisms, and is an emerging target for treatment of human ....The endosome at atomic resolution. The project seeks to improve understanding of intracellular transport. The transport of proteins is essential for controlling the interactions of a cell with its environment, and for regulating a huge number of cell signalling events. The retromer protein complex is a central mediator of intracellular trafficking in organelles called endosomes. It is vital for normal cell homeostasis in all eukaryotic organisms, and is an emerging target for treatment of human neurodegenerative diseases. This project plans to use a combination of cutting-edge X-ray crystallographic and electron microscopy approaches to develop a multi-scale, pseudo-atomic structure of retromer and key regulatory proteins to understand how this multi-component protein machinery is assembled to control intracellular transport.Read moreRead less