"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
Engineering new tools to aid structure determination of membrane proteins. This project aims to address the inherent instability of G protein-coupled receptors (GPCRs), which are cell-surface proteins that are a major drug targets. The instability of GPCRs has resulted in a lack of atomic-level structural information that has hindered structure-based drug discovery efforts. This project expects to develop tools to improve GPCR stability and streamline the structure determination process. Project ....Engineering new tools to aid structure determination of membrane proteins. This project aims to address the inherent instability of G protein-coupled receptors (GPCRs), which are cell-surface proteins that are a major drug targets. The instability of GPCRs has resulted in a lack of atomic-level structural information that has hindered structure-based drug discovery efforts. This project expects to develop tools to improve GPCR stability and streamline the structure determination process. Project outcomes are intended to lead to significant advances in membrane protein structure determination and will have a substantial impact on future research in the pharmaceutical industry.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
Discovery Early Career Researcher Award - Grant ID: DE210101479
Funder
Australian Research Council
Funding Amount
$450,948.00
Summary
The investigation of an unconventional Human Leukocyte Antigen molecule. This project aims to characterise a unique and understudied surface molecule (HLA-E). The immune system is activated and regulated by a complex set of molecules including HLA molecules present on the cell surface that inform the immune system of infection. Therefore, this project expects to generate new knowledge in the areas of cellular biology and immunology by utilising a cutting-edge and multi-disciplinary approach. Exp ....The investigation of an unconventional Human Leukocyte Antigen molecule. This project aims to characterise a unique and understudied surface molecule (HLA-E). The immune system is activated and regulated by a complex set of molecules including HLA molecules present on the cell surface that inform the immune system of infection. Therefore, this project expects to generate new knowledge in the areas of cellular biology and immunology by utilising a cutting-edge and multi-disciplinary approach. Expected outcomes of this project include the generation of new knowledge of this unconventional molecule and its interaction with immune cells. This should provide significant impacts by defining the non-conventional role of HLA-E within the immune system, which may advise future research into vaccines or therapeutics. 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
Discovery Early Career Researcher Award - Grant ID: DE220101221
Funder
Australian Research Council
Funding Amount
$453,614.00
Summary
Revealing bat antibody recognition mechanism against bat-borne viruses. Bats act as asymptomic reservoir hosts for numerous zoonotic viruses that are lethal in humans, indicating that the bat immune system can control these viruses. However, little is known about bat immunity including how bat antibodies recognise bat-borne viruses. This project aims to study bat anti-viral antibodies by utilising innovative protein engineering, cutting-edge cryo-EM technology and single-cell isolation and seque ....Revealing bat antibody recognition mechanism against bat-borne viruses. Bats act as asymptomic reservoir hosts for numerous zoonotic viruses that are lethal in humans, indicating that the bat immune system can control these viruses. However, little is known about bat immunity including how bat antibodies recognise bat-borne viruses. This project aims to study bat anti-viral antibodies by utilising innovative protein engineering, cutting-edge cryo-EM technology and single-cell isolation and sequencing. The project seeks to uncover bat-borne zoonotic virus glycoprotein architecture and reveal how bat antibodies function to inhibit viral infection. Expected outcomes will be new insight and tools to combat emerging and yet to emerge pathogens, enabling pandemic preparedness and increasing global biosecurity.
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Discovery Early Career Researcher Award - Grant ID: DE210101137
Funder
Australian Research Council
Funding Amount
$458,665.00
Summary
Exploiting biological noise for next generation electrochemical biosensors. This project aims to harness the intrinsic noise in a biological system to develop a new platform for biosensors. This will lead to advancement of a new versatile electrochemical platform for real-time screening with vast applications that span from sensing at sub-cellular level to point-of-care and implantable biosensors. The new sensory technique will improve the specificity, sensitivity and resolution in biosensors an ....Exploiting biological noise for next generation electrochemical biosensors. This project aims to harness the intrinsic noise in a biological system to develop a new platform for biosensors. This will lead to advancement of a new versatile electrochemical platform for real-time screening with vast applications that span from sensing at sub-cellular level to point-of-care and implantable biosensors. The new sensory technique will improve the specificity, sensitivity and resolution in biosensors and enables measurement of multiple biomarkers simultaneously in real-time. The outcomes will contribute to a better understanding of fundamental physiological processes and chemical interactions at subcellular level which will inform future advancements in biomedical engineering.
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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