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
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
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
Anticipating, Combating and Exploiting the Evolution of Pesticide Resistance in Australian Agricultural Pests and Disease Vectors. Synthetic insecticides have resulted in an explosion in food production through effective insect control. However, insects have begun to evolve resistance against one of the most widely used classes of insecticides (organophosphates) via mutations in carboxylesterases (CBEs). To address this problem, the ability to anticipate further evolution, combat it and exploit ....Anticipating, Combating and Exploiting the Evolution of Pesticide Resistance in Australian Agricultural Pests and Disease Vectors. Synthetic insecticides have resulted in an explosion in food production through effective insect control. However, insects have begun to evolve resistance against one of the most widely used classes of insecticides (organophosphates) via mutations in carboxylesterases (CBEs). To address this problem, the ability to anticipate further evolution, combat it and exploit it for our own benefit is needed. This project aims to anticipate evolution by simulating it in the laboratory, allowing for the best preparation for change. New pesticides will be designed to combat insecticide resistance based upon the molecular structure of an insect CBE. This project aims to exploit these newly evolved enzymes to create biosensors and decontamination agents.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100085
Funder
Australian Research Council
Funding Amount
$450,000.00
Summary
Regional facility for macromolecular x-ray crystallography. This facility in the southern NSW/ACT region will allow research into structures of biological molecules. Research at the facility will contribute to advances in understanding of processes in living organisms, new drugs and new biotechnology with national and international significance.