Molecular mechanisms of mechanosensation and shape regulation in cells. This project aims to explore how cells physically sense and respond to the surrounding environment on a molecular level. Physical distortion of erythrocytes doubles their glucose consumption and increases cation membrane flux five-fold. This mechanism involves opening of the mechanosenstive ion channel Piezo1. This project will include a kinetic description of these phenomena, with a goal to establish a predictive mathematic ....Molecular mechanisms of mechanosensation and shape regulation in cells. This project aims to explore how cells physically sense and respond to the surrounding environment on a molecular level. Physical distortion of erythrocytes doubles their glucose consumption and increases cation membrane flux five-fold. This mechanism involves opening of the mechanosenstive ion channel Piezo1. This project will include a kinetic description of these phenomena, with a goal to establish a predictive mathematical model of the regulation of cell-shape and volume. The project will provide an understanding of mechanisms operating when cells and tissues are succumbing to trauma and invasion, and how to control these processes on a molecular level.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100046
Funder
Australian Research Council
Funding Amount
$289,381.00
Summary
A fast fluorescence lifetime imaging microscope to track protein dynamics. This project aims to establish a fast fluorescence lifetime imaging microscope that can track the intracellular journey of a protein throughout the entire structural framework of a living cell. By coupling single particle tracking technology with a cutting-edge fluorescence lifetime camera, this one-of-a-kind microscope will enable protein mobility and interaction to be spatially mapped with unprecedented temporal resolut ....A fast fluorescence lifetime imaging microscope to track protein dynamics. This project aims to establish a fast fluorescence lifetime imaging microscope that can track the intracellular journey of a protein throughout the entire structural framework of a living cell. By coupling single particle tracking technology with a cutting-edge fluorescence lifetime camera, this one-of-a-kind microscope will enable protein mobility and interaction to be spatially mapped with unprecedented temporal resolution. The benefit of this technology is that it will enable scientists in Australia to image, for the first time, the biophysical mechanism by which a protein navigates intracellular architecture to regulate a complex biological function at the single molecule level.Read moreRead less
Detecting stress-induced changes to subcellular copper pools in brain cells. Copper (Cu) plays essential roles in the functioning of brain cells, but the regulation and activity of this metal is poorly understood. This project aims to map sub-cellular Cu pools in brain cells, with particular emphasis on the effects of cellular stresses on these pools. These studies are expected to contribute important new methods for the study of Cu biology, and could provide valuable information about how Cu ho ....Detecting stress-induced changes to subcellular copper pools in brain cells. Copper (Cu) plays essential roles in the functioning of brain cells, but the regulation and activity of this metal is poorly understood. This project aims to map sub-cellular Cu pools in brain cells, with particular emphasis on the effects of cellular stresses on these pools. These studies are expected to contribute important new methods for the study of Cu biology, and could provide valuable information about how Cu homeostasis is maintained or perturbed under various stresses. In the future, this work is expected to form the basis of studies of brain Cu pools in neurodegenerative diseases.Read moreRead less
Methods for Protein Structure Analysis by Electron Paramagnetic Resonance. This highly interdisciplinary project aims to establish new tools to analyse the structure and motions of proteins that are otherwise difficult to study. A combination of advanced biochemistry, modern magnetic spectroscopy methods, and high-performance computing techniques will be applied to study proteins at physiological concentrations and in complex environments. New techniques will be developed and tested on proteins ....Methods for Protein Structure Analysis by Electron Paramagnetic Resonance. This highly interdisciplinary project aims to establish new tools to analyse the structure and motions of proteins that are otherwise difficult to study. A combination of advanced biochemistry, modern magnetic spectroscopy methods, and high-performance computing techniques will be applied to study proteins at physiological concentrations and in complex environments. New techniques will be developed and tested on proteins of high biochemical or biomedical importance, and the approach will be applied to established drug targets.Read moreRead less
Protein design. This project aims to design binding specificity in proteins in a rational way. Extending the existing repertoire of protein specificity using engineering principles should harness the catalytic power and high binding affinities of natural proteins. By building upon protein design algorithms, this project will develop biosensors for neurotransmitters and specialist enzymes to incorporate unnatural amino acids. It will iteratively improve the designs and algorithms by computational ....Protein design. This project aims to design binding specificity in proteins in a rational way. Extending the existing repertoire of protein specificity using engineering principles should harness the catalytic power and high binding affinities of natural proteins. By building upon protein design algorithms, this project will develop biosensors for neurotransmitters and specialist enzymes to incorporate unnatural amino acids. It will iteratively improve the designs and algorithms by computational and experimental characterisation. The outcomes should address the long-standing need in synthetic biology for a facile route to designer proteinsRead moreRead less
Three-dimensional structure determination of biomolecular assemblies from sparse data of different length scales. New computer algorithms will be combined with sparse experimental structure restraints, obtained with novel protein chemistry technologies, to generate accurate three-dimensional (3D) models of proteins and protein assemblies in solution and in the solid state. The new strategies will greatly increase the number of protein targets amenable to rational drug design.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100027
Funder
Australian Research Council
Funding Amount
$320,000.00
Summary
Sensitive and multinuclear: a dedicated facility for high-throughput characterisation of small molecules. This project will provide new cutting edge nuclear magnetic resonance equipment will enhance an existing shared analysis facility based at University of New South Wales. The new equipment will underpin research in polymers, neuropharmacology, the biological basis of inherited disease, nanomedicine, bioactive compounds and toxins.
Expanding the molecular tool set for structural studies of proteins and their complexes. Many applications in medical science and drug development depend on our ability to determine the 3D structures of proteins, protein assemblies and protein-ligand complexes. This project will develop novel lanthanide-binding tags and crosslinking agents that can be coupled to unnatural amino acids introduced into proteins with advanced protein chemistry techniques. These new tools will facilitate the collecti ....Expanding the molecular tool set for structural studies of proteins and their complexes. Many applications in medical science and drug development depend on our ability to determine the 3D structures of proteins, protein assemblies and protein-ligand complexes. This project will develop novel lanthanide-binding tags and crosslinking agents that can be coupled to unnatural amino acids introduced into proteins with advanced protein chemistry techniques. These new tools will facilitate the collection of structure restraints by nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR) and mass spectrometry, which are needed to generate accurate models of proteins and their complexes with other molecules. Major beneficial outcome will include an increase in the number of protein targets amenable to rational drug design and improved methods for generating new drug leads.Read moreRead less
Nano-reactors: Protein cages as reusable scaffolds for designer enzymes. This project aims to develop robust protein cages derived from the coats of viruses to contain heat-stable P450 enzymes, for use as specialised protein bio-catalysts in chemical industries. A valuable chemical precursor of renewable bio-plastics will be produced from seed oils by enzymes, reducing the use of fossil fuels. This synthetic biology approach combines biotechnology, nanotechnology and protein engineering to estab ....Nano-reactors: Protein cages as reusable scaffolds for designer enzymes. This project aims to develop robust protein cages derived from the coats of viruses to contain heat-stable P450 enzymes, for use as specialised protein bio-catalysts in chemical industries. A valuable chemical precursor of renewable bio-plastics will be produced from seed oils by enzymes, reducing the use of fossil fuels. This synthetic biology approach combines biotechnology, nanotechnology and protein engineering to establish a plant-based platform biotechnology for using enzymes as catalysts to make high-value molecules. The project aims to show how to engineer clean, sustainable chemistry in designer nano-environments. This should make synthetic processes more sustainable and enhance advanced chemical manufacturing in Australia.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100122
Funder
Australian Research Council
Funding Amount
$725,000.00
Summary
Hydrogen-deuterium exchange system - a missing link in protein analysis . Proteins are highly dynamic molecules that are essential to life. This project aims to acquire a fully automated and integrated hydrogen-deuterium exchange system, a powerful tool for analysing the motion of proteins and their interactions with other molecules. Expected outcomes include a new capability for biology labs around Australia by (1) increasing success rates of difficult projects that aim to visualise 3D protein ....Hydrogen-deuterium exchange system - a missing link in protein analysis . Proteins are highly dynamic molecules that are essential to life. This project aims to acquire a fully automated and integrated hydrogen-deuterium exchange system, a powerful tool for analysing the motion of proteins and their interactions with other molecules. Expected outcomes include a new capability for biology labs around Australia by (1) increasing success rates of difficult projects that aim to visualise 3D protein structures and (2) providing rapid information about protein interaction sites. Anticipated benefits include the generation of dynamic data that will be highly complementary to static pictures of protein structures. This will enable clever design of new proteins with beneficial uses in the biotechnology industry.Read moreRead less