"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
Uncovering the molecular mechanisms of potassium channel activity. The aim of this project is to determine the mechanisms of protein-mediated potassium ion transport across cell membranes. It will combine advanced simulations, structural biology and electrophysiology to describe the detailed molecular processes underscoring calcium-activated potassium channel conduction, gating and inactivation. The expected outcome is an improved description of how ion channels recognise and respond to physiolo ....Uncovering the molecular mechanisms of potassium channel activity. The aim of this project is to determine the mechanisms of protein-mediated potassium ion transport across cell membranes. It will combine advanced simulations, structural biology and electrophysiology to describe the detailed molecular processes underscoring calcium-activated potassium channel conduction, gating and inactivation. The expected outcome is an improved description of how ion channels recognise and respond to physiological stimuli to control electrical signalling the body. Our results will provide benefits in the form of basic understanding relevant to ion transport phenomena in biological systems, and atomic-level views of nervous system function to guide future directions in pharmacology.Read moreRead less
An investigation into T cell immunity towards metabolites. This project aims to investigate how the immune system responds to small molecule metabolites, an emerging area in the life sciences about which little is known. The project aims to combine innovative mass spectrometry, structural and biochemical approaches to learn how metabolites are presented to specific T lymphocytes by an antigen presenting molecule called MR1. Outcomes are expected to transform the current understanding of the mol ....An investigation into T cell immunity towards metabolites. This project aims to investigate how the immune system responds to small molecule metabolites, an emerging area in the life sciences about which little is known. The project aims to combine innovative mass spectrometry, structural and biochemical approaches to learn how metabolites are presented to specific T lymphocytes by an antigen presenting molecule called MR1. Outcomes are expected to transform the current understanding of the molecular basis underpinning metabolite-mediated immunity. Significant benefits are anticipated to include fundamental new knowledge about immunity that may ultimately be used by the biotechnology industry.Read moreRead less
Engineering a chromatin looping factor for artificial gene regulation. This project aims to define mechanisms of chromatin looping and gene activation by a widely expressed mammalian protein. The project will establish if the functions of this protein are modulated by the binding of small molecules, whether it can act in conjunction with closely related proteins, and if post-translational modifications regulate looping and gene activation. Using protein engineering the project will develop synth ....Engineering a chromatin looping factor for artificial gene regulation. This project aims to define mechanisms of chromatin looping and gene activation by a widely expressed mammalian protein. The project will establish if the functions of this protein are modulated by the binding of small molecules, whether it can act in conjunction with closely related proteins, and if post-translational modifications regulate looping and gene activation. Using protein engineering the project will develop synthetic looping factors that can switch on a wide array of target genes. The project aims to answer fundamental questions about how proteins can establish and maintain physical loops in DNA to modulate gene expression. The project will also develop research tools that might ultimately correct diseases caused by the faulty expression of genes.Read moreRead less
The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyami ....The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyamines, as we have discovered that polyamines are regulated by iron at 2-major levels, involving >10-key polyamine pathway proteins. This proposal represents first-in-field studies specifically designed to dissect mechanisms involved in this relationship. Our Central Hypothesis is that iron regulates polyamine metabolism.Read moreRead less
A novel platform-technology for long-term subcutaneous neurophysiology. This project aims to develop a novel miniature device for subcutaneous and tetherless brain sensing. It addresses the lack of a device solution for brain-sensing that combines ultra-long-term reliable sensing capability and small dimensions for minimally-invasive procedures. We achieve this through our novel electrode architecture that significantly enhances the quality and reliability of recorded brain signals. We introduce ....A novel platform-technology for long-term subcutaneous neurophysiology. This project aims to develop a novel miniature device for subcutaneous and tetherless brain sensing. It addresses the lack of a device solution for brain-sensing that combines ultra-long-term reliable sensing capability and small dimensions for minimally-invasive procedures. We achieve this through our novel electrode architecture that significantly enhances the quality and reliability of recorded brain signals. We introduce a platform technology designed for subscalp anatomy with future use in various brain-machine interfacing applications relying on reliable, long-term and easy-to-implant systems. This project's device manufacturing, training, and intellectual property are expected to strengthen Australia's position in bioelectronics.Read moreRead less
Biophysics-informed deep learning framework for magnetic resonance imaging. This project aims to bring about a paradigm shift from the conventional non-quantitative magnetic resonance imaging to ultra-fast, quantitative, and artefact free imaging. This project integrates biophysics and artificial intelligence, and it is expected to bring new knowledge in both fields. The expected outcomes of this project include next generation magnetic resonance imaging methods with a fundamental shift in the ....Biophysics-informed deep learning framework for magnetic resonance imaging. This project aims to bring about a paradigm shift from the conventional non-quantitative magnetic resonance imaging to ultra-fast, quantitative, and artefact free imaging. This project integrates biophysics and artificial intelligence, and it is expected to bring new knowledge in both fields. The expected outcomes of this project include next generation magnetic resonance imaging methods with a fundamental shift in the approach to image artefacts and image quantification. This project is expected to advance both single subject and population level biomedical imaging with greater accuracy and cost-effectiveness. This project also promotes explainable and generalisable artificial intelligence in medical imaging.Read moreRead less
Probing the role of dynamics in protein modulation of GPCR phenotype . Life relies upon the fundamental ability to convert external stimuli into an appropriate biological response. Such stimuli are transmitted by cell surface proteins (receptors), which convert this stimulus into an intracellular signal. The largest group of cell surface receptors is the G protein-coupled receptor (GPCR) family. Despite advances in GPCR structure determination, many questions regarding the structural basis of GP ....Probing the role of dynamics in protein modulation of GPCR phenotype . Life relies upon the fundamental ability to convert external stimuli into an appropriate biological response. Such stimuli are transmitted by cell surface proteins (receptors), which convert this stimulus into an intracellular signal. The largest group of cell surface receptors is the G protein-coupled receptor (GPCR) family. Despite advances in GPCR structure determination, many questions regarding the structural basis of GPCR function and signalling remain unanswered. The primary outcome of this project is to provide mechanistic insight into the dynamics of GPCR ligand recognition and activation to advance our understanding of GPCR signal transduction, a fundamental biological process for all living organisms.Read moreRead less
Dark-field: A new kind of x-ray imaging. This project aims to develop new x-ray imaging capabilities that look inside an object and map out those details that are too small to be seen directly, by extracting the dark-field which is produced as x-ray light scatters. Dark-field images can reveal tiny cracks in manufactured parts, discover powdered explosives or drugs during security screening, and detect changes in the size of the many tiny air sacs in the lungs. Expected outcomes of this project ....Dark-field: A new kind of x-ray imaging. This project aims to develop new x-ray imaging capabilities that look inside an object and map out those details that are too small to be seen directly, by extracting the dark-field which is produced as x-ray light scatters. Dark-field images can reveal tiny cracks in manufactured parts, discover powdered explosives or drugs during security screening, and detect changes in the size of the many tiny air sacs in the lungs. Expected outcomes of this project include new instruments and methods of analysis that will allow x-ray dark-field imaging to be quantitative and widely adopted. These methods should benefit non-invasive multi-scale imaging at the Australian Synchrotron and equip x-ray imaging in industry, security and healthcare.Read moreRead less
Nanoelectromechanical Mass Spectrometry with Molecular Imaging. This project aims to develop new technology to enable simultaneous measurement of the mass and conformation of single molecules. Mass spectrometry and high-resolution microscopy are independent analytical tools used widely to characterise the chemical and physical properties of molecules. This project aims to develop new technology based on advanced nanoelectromechanical systems that combines the capabilities of these complementary ....Nanoelectromechanical Mass Spectrometry with Molecular Imaging. This project aims to develop new technology to enable simultaneous measurement of the mass and conformation of single molecules. Mass spectrometry and high-resolution microscopy are independent analytical tools used widely to characterise the chemical and physical properties of molecules. This project aims to develop new technology based on advanced nanoelectromechanical systems that combines the capabilities of these complementary instruments. This would enable synchronous measurement of molecular mass and conformation with nanometre resolution. In contrast to current mass spectrometry, this technology could be operated in fluid and detect neutral species. This significant change in capability could be applied to advance biological and medical research.Read moreRead less