The effect of methylation and phosphorylation on ribosome function. This project aims to discover how cells regulate ribosome function and selectivity, by modifying their ribosomal proteins. This affects protein synthesis, a process which is central to the growth of all living things. Expected outcomes include new knowledge on the regulation of protein synthesis, improved techniques for the study of this process and an enhanced capacity for international collaboration. New avenues for the artifi ....The effect of methylation and phosphorylation on ribosome function. This project aims to discover how cells regulate ribosome function and selectivity, by modifying their ribosomal proteins. This affects protein synthesis, a process which is central to the growth of all living things. Expected outcomes include new knowledge on the regulation of protein synthesis, improved techniques for the study of this process and an enhanced capacity for international collaboration. New avenues for the artificial regulation of the ribosome may also emerge, relevant to synthetic biology and the engineering of industrial yeasts. The project should provide significant new findings for the research community, generate research citations and contribute to a highly skilled workforce by the training of staff and students.Read moreRead less
How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misf ....How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misfolded proteins during ageing, within the nervous system of a living animal. Expected outcomes of this project will generate new knowledge of brain physiology and ageing relevant to all animals. This should provide significant benefits, such as a greater understanding of long-term brain functions including memory.Read moreRead less
Mechanisms of memory function involving site-specific tau phosphorylation. This project aims to understand the molecular principles that facilitate encoding, maintenance and retrieval of memories in the brain. To store memories in brain circuits, electrical and chemical signals are crucial. Brain cells can integrate signals into biochemical modifications of intracellular proteins. The nature of the protein modifications that represent memory within brain cells is unknown. This project uses innov ....Mechanisms of memory function involving site-specific tau phosphorylation. This project aims to understand the molecular principles that facilitate encoding, maintenance and retrieval of memories in the brain. To store memories in brain circuits, electrical and chemical signals are crucial. Brain cells can integrate signals into biochemical modifications of intracellular proteins. The nature of the protein modifications that represent memory within brain cells is unknown. This project uses innovative genome editing, mathematical modelling and proteomic approaches, to study how biochemical modifications of a key protein called tau help encode and retrieve memories. These molecular insights will make a significant advance in the current understanding of a brain function that is essential to all human activities.Read moreRead less
Molecular control of memory traces. This project aims to understand how particular molecules help encode memories in the brain for future retrieval. Individual memories are encoded in brain cells through an unknown physical process. This project uses innovative approaches to manipulate memory-containing cells and will provide a new detailed explanation of memory. Outcomes of this work will significantly advance the current understanding of how memories are physically generated and maintained, wh ....Molecular control of memory traces. This project aims to understand how particular molecules help encode memories in the brain for future retrieval. Individual memories are encoded in brain cells through an unknown physical process. This project uses innovative approaches to manipulate memory-containing cells and will provide a new detailed explanation of memory. Outcomes of this work will significantly advance the current understanding of how memories are physically generated and maintained, which is an essential component of human and animal life. This research provides significant benefits in understanding the biology behind memory and in maintaining memory capacity in ageing.
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Characterising a novel stress-sensing signalling factor. Aim: To understand how phosphorylation regulates signalling pathways to allow metabolic adaptations in response to energetic stress. Significance: A fundamental understanding of the activation of signalling pathways via phosphorylation is vital for our knowledge of homeostasis and the mechanisms controlling cell survival. Expected outcomes: To generate new systems biology and physiology data to understand how the stress response is regulat ....Characterising a novel stress-sensing signalling factor. Aim: To understand how phosphorylation regulates signalling pathways to allow metabolic adaptations in response to energetic stress. Significance: A fundamental understanding of the activation of signalling pathways via phosphorylation is vital for our knowledge of homeostasis and the mechanisms controlling cell survival. Expected outcomes: To generate new systems biology and physiology data to understand how the stress response is regulated and characterise new stress-sensing pathways. Benefits: A greater understanding of the molecular mechanisms controlling metabolism in response to stress has extremely broad applications to improve metabolic efficiency in fields ranging from exercise- and life-sciences to agriculture.Read moreRead less
"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
Deciphering new regulators of lipid metabolism: a focus on lipid droplets . Lipid droplets store lipids in cells and the mitochondria break down this lipid to generate energy. Both organelles are critical for energy metabolism and cell survival. This project aims to determine the proteins that regulate the interaction between mitochondria and lipid droplets, and how these proteins regulate metabolism. It is anticipated that this project will identify the essential components of lipid droplet-mit ....Deciphering new regulators of lipid metabolism: a focus on lipid droplets . Lipid droplets store lipids in cells and the mitochondria break down this lipid to generate energy. Both organelles are critical for energy metabolism and cell survival. This project aims to determine the proteins that regulate the interaction between mitochondria and lipid droplets, and how these proteins regulate metabolism. It is anticipated that this project will identify the essential components of lipid droplet-mitochondria interactions and their impact on regulating cellular lipid metabolism. The intended outcome of this project is to provide fundamental new knowledge in understanding how organelles interact and how lipid metabolism is regulated. This knowledge has applications for the primary industries and biotechnology sector.Read moreRead less
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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