"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
Mechanism of AMPK activation by drugs and metabolites. This project aims to identify the molecular basis of activation mechanisms in the AMP-activated protein kinase (AMPK), an enzyme that regulates burning and storage of fuels such as fat and sugars, autophagy and controls appetite and energy expenditure. This project expects to provide insights into how energy metabolism and physiological functions are linked.
How auto-transporter proteins mediate bacterial interactions. This project aims to investigate the structure-function relationships that underpin key auto-transporter roles in bacterial cell adhesion, aggregation and biofilm formation. Auto-transporter proteins are extremely common in bacteria where they play a central role in controlling bacterial interactions with other bacteria, with human cells, and with surfaces. This project will define the molecular mechanisms underlying these processes. ....How auto-transporter proteins mediate bacterial interactions. This project aims to investigate the structure-function relationships that underpin key auto-transporter roles in bacterial cell adhesion, aggregation and biofilm formation. Auto-transporter proteins are extremely common in bacteria where they play a central role in controlling bacterial interactions with other bacteria, with human cells, and with surfaces. This project will define the molecular mechanisms underlying these processes. This will have significant benefits, such as providing the basis for the development of approaches to block auto-transporter functions that contribute to the establishment of persistent and difficult to treat bacterial infections.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE150100163
Funder
Australian Research Council
Funding Amount
$560,000.00
Summary
Single molecule imaging laboratory. Single molecule imaging laboratory: The goal of the project is to establish a single molecule imaging laboratory to close the gap between structural imaging and cellular imaging. Utilising the expertise of the ARC Centre of Excellence in Advanced Molecular Imaging, the aim of the project is to design, build and apply three microscopes that go beyond the current commercial solutions for single molecule localisation microscopy such as Photo-Activation Localisati ....Single molecule imaging laboratory. Single molecule imaging laboratory: The goal of the project is to establish a single molecule imaging laboratory to close the gap between structural imaging and cellular imaging. Utilising the expertise of the ARC Centre of Excellence in Advanced Molecular Imaging, the aim of the project is to design, build and apply three microscopes that go beyond the current commercial solutions for single molecule localisation microscopy such as Photo-Activation Localisation Microscopy (PALM) and Stochastic Optical Reconstruction Microscopy (STORM) and perform single molecule imaging: deep inside cells and tissue.The facility will have a fast acquisition rate to monitor highly dynamic molecular events, and improved precision to image molecules and complexes in intact cells with less than or equal to one nanometre resolution. There is currently no comparable imaging facility in the world.Read moreRead less
The mechanism of membrane disruption by antimicrobial peptides. Bacterial resistance to antibiotics is a growing crisis in modern medicine. Antibacterial peptides from Australian frogs represent a new class of potent and selective antibacterial agents. Understanding how these peptides kill bacteria but not vertebrate cells could lead to the design of new drugs for pharmaceutical and/or clinical purposes.
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
Understanding how RNA editing regulates RNA fate. This project aims to address how RNA editing mediated by ADAR1 alters the interactions of targeted RNA with the innate immune sensing system. ADAR1 editing converts adenosine to inosine within double stranded RNA. It is known that this is key to prevent activation of the innate immune sensor MDA5 by endogenous RNA. However, we do not understand why edited RNA is tolerated and unedited RNA is not. This project will generate new knowledge regarding ....Understanding how RNA editing regulates RNA fate. This project aims to address how RNA editing mediated by ADAR1 alters the interactions of targeted RNA with the innate immune sensing system. ADAR1 editing converts adenosine to inosine within double stranded RNA. It is known that this is key to prevent activation of the innate immune sensor MDA5 by endogenous RNA. However, we do not understand why edited RNA is tolerated and unedited RNA is not. This project will generate new knowledge regarding the effect of editing on how endogenous RNA is perceived by the innate immune system.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100043
Funder
Australian Research Council
Funding Amount
$435,279.00
Summary
High-throughput portable and wearable device fabrication facility. This project aims to establish a fabrication and characterisation facility for high-throughput production of portable, wearable and stretchable biomedical devices to accelerate the design–fabrication–evaluation process and save ‘trial-and-error’ costs during optimisation turnaround. It will apply computer-aided design for the programmable synthesis of hybrid materials for high-throughput screening of disease biomarkers, and super ....High-throughput portable and wearable device fabrication facility. This project aims to establish a fabrication and characterisation facility for high-throughput production of portable, wearable and stretchable biomedical devices to accelerate the design–fabrication–evaluation process and save ‘trial-and-error’ costs during optimisation turnaround. It will apply computer-aided design for the programmable synthesis of hybrid materials for high-throughput screening of disease biomarkers, and super-solution imaging of single molecules in live cells. This facility will provide capability for researchers pursuing industry transformation and other initiatives in the development of advanced materials, biomolecular sciences, nanotechnology, photonics and device engineering.Read moreRead less
Industrial Transformation Research Hubs - Grant ID: IH150100028
Funder
Australian Research Council
Funding Amount
$3,708,510.00
Summary
ARC Research Hub for Integrated Device for End-user Analysis at Low-levels. ARC Research Hub for Integrated Device for End-user Analysis at Low-levels. This hub aims to improve detection of biological materials by building a portable device for rapid, time-critical detection of low-abundance molecular and cellular analytes. It is expected that the resulting technologies would be used at medical points of care, ordinary workplaces and centres of activity to test for tiny levels of targeted molecu ....ARC Research Hub for Integrated Device for End-user Analysis at Low-levels. ARC Research Hub for Integrated Device for End-user Analysis at Low-levels. This hub aims to improve detection of biological materials by building a portable device for rapid, time-critical detection of low-abundance molecular and cellular analytes. It is expected that the resulting technologies would be used at medical points of care, ordinary workplaces and centres of activity to test for tiny levels of targeted molecules. The initial focus would be early diagnosis of disease and point-of-care drug testing for humans and animals, but the technology platform could be used to sample food and environmental toxins. The hub expects these disruptive technologies will make Australian biotechnology, diagnostics, veterinary, agribusiness and manufacturing firms globally competitive.Read moreRead less