Development of New Generation Magnetic Circular Dichroism Spectrometers. We are building two Magnetic Circular Dichroism (MCD spectrometers) to meet a rising need in the study of metallo-proteins and other molecules of biological interest. The PhD project described in this application will involve instrumentation design, interfacing and sampling handling development for biological samples. We wish to involve a Lastek, a scientific instrumentation company, in the possible commercial development o ....Development of New Generation Magnetic Circular Dichroism Spectrometers. We are building two Magnetic Circular Dichroism (MCD spectrometers) to meet a rising need in the study of metallo-proteins and other molecules of biological interest. The PhD project described in this application will involve instrumentation design, interfacing and sampling handling development for biological samples. We wish to involve a Lastek, a scientific instrumentation company, in the possible commercial development of aspects of this project.Read moreRead less
Elucidating the mechanisms by which Scribble, Discs Large and Lethal Giant Larvae regulate epithelial polarity. Discs Large (Dlg) and Scribble are proteins that regulate cell shape by concentrating at particular regions within the cell and recruiting other proteins to that region. It is thought that the two proteins interact with each other, and with other proteins involved in protein trafficking and cell architecture, but it is not known how these events coordinate to produce a net outcome on ....Elucidating the mechanisms by which Scribble, Discs Large and Lethal Giant Larvae regulate epithelial polarity. Discs Large (Dlg) and Scribble are proteins that regulate cell shape by concentrating at particular regions within the cell and recruiting other proteins to that region. It is thought that the two proteins interact with each other, and with other proteins involved in protein trafficking and cell architecture, but it is not known how these events coordinate to produce a net outcome on cell shape. To answer these questions, the dynamic events involved in localization of Dlg, Scribble, and associated proteins will be determined, in mammalian cells and in whole organs of the vinegar fly.Read moreRead less
Profiling tissue protein, elemental ions and nanoparticle distributions. This project aims to investigate protein-protein interactions that are crucial to homeostatic cell signalling and viability in a changing tissue environment. The central goal is to develop and validate protocols to combine cutting-edge tissue imaging modalities to map and characterise tissue distributions of native and modified proteins, elemental ions and pharmacological agents including nanoparticles and nanovehicles. The ....Profiling tissue protein, elemental ions and nanoparticle distributions. This project aims to investigate protein-protein interactions that are crucial to homeostatic cell signalling and viability in a changing tissue environment. The central goal is to develop and validate protocols to combine cutting-edge tissue imaging modalities to map and characterise tissue distributions of native and modified proteins, elemental ions and pharmacological agents including nanoparticles and nanovehicles. The aim is to use novel tissue scanning mass spectrometry techniques in conjunction with X-ray-based microprobe spectroscopy and advanced multi-parameter cytometry to identify spatial distributions of proteins, ions and drugs in tissues. This approach may provide new information about the maintenance of homeostatic control and the content, distribution and potential metabolism of drugs or nanoparticles within biological tissues.Read moreRead less
Developing orthogonal synthetic signaling cascades. This project proposes a generic approach for the construction of molecular switches based on artificially autoinhibited proteases. The bottom-up design of protein-based signaling networks is a key goal of synthetic biology. Yet, this remains elusive due to our inability to tailor-make signal transducers and receptors that can be readily compiled into defined signaling networks. Using structure-guided design and directed protein evolution, a set ....Developing orthogonal synthetic signaling cascades. This project proposes a generic approach for the construction of molecular switches based on artificially autoinhibited proteases. The bottom-up design of protein-based signaling networks is a key goal of synthetic biology. Yet, this remains elusive due to our inability to tailor-make signal transducers and receptors that can be readily compiled into defined signaling networks. Using structure-guided design and directed protein evolution, a set of protease-based signal transducers and ligand activated allosteric receptors will be created. The developed components are intended to be used to construct artificial signaling networks in mammalian cells that are orthogonal to the endogenous signaling cascades.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190100609
Funder
Australian Research Council
Funding Amount
$368,000.00
Summary
Mechanobiology: a new model of integrin activation by membrane tension. This project aims to address a fundamental question in mechanobiology on how integrin receptor coordinates with force to mediate cell spreading, migration, growth and survival. With an observation that membrane deformation enhances integrin binding, the project expects to establish a new model of integrin activation by membrane tension. It will develop an integrated approach combining single-molecule force probes, super reso ....Mechanobiology: a new model of integrin activation by membrane tension. This project aims to address a fundamental question in mechanobiology on how integrin receptor coordinates with force to mediate cell spreading, migration, growth and survival. With an observation that membrane deformation enhances integrin binding, the project expects to establish a new model of integrin activation by membrane tension. It will develop an integrated approach combining single-molecule force probes, super resolution microscopy, microfluidics and molecular dynamics simulations. It is expected that the role of membrane tension in promoting cell adhesion will be defined at molecular scale, and the link between integrin activation and Piezo calcium channel mediated membrane tension sensing will be delineated.Read moreRead less
Iron, ferroptosis and the biology of ageing. This project aims to determine how and when regulation of iron is lost. Failing iron metabolism during life may dictate the rate of ageing by driving a newly discovered cell death program. Combining biology, chemistry and physics, this collaborative project aims to transform the understanding of the fundamental mechanisms of biological ageing. Anticipated outcomes include new assays for measuring iron in biology and identification of potential pathway ....Iron, ferroptosis and the biology of ageing. This project aims to determine how and when regulation of iron is lost. Failing iron metabolism during life may dictate the rate of ageing by driving a newly discovered cell death program. Combining biology, chemistry and physics, this collaborative project aims to transform the understanding of the fundamental mechanisms of biological ageing. Anticipated outcomes include new assays for measuring iron in biology and identification of potential pathways that regulate death signaling and lifespan. Outcomes will benefit life sciences and biotechnology industries.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100179
Funder
Australian Research Council
Funding Amount
$3,189,000.00
Summary
Automated high resolution and high contrast cryo -TEM for three-dimensional structural biology. This project aims to establish a facility in automated, single-particle cryo-TEM and cryo-TEM tomography (Titan Krios) that will enable atomic and molecular structure research and three-dimensional subcellular and cellular imaging. The project will span all multiscale cryo-TEM modalities from the visualisation of cells, membranes and macromolecular complexes, through to near-atomic-resolution protein ....Automated high resolution and high contrast cryo -TEM for three-dimensional structural biology. This project aims to establish a facility in automated, single-particle cryo-TEM and cryo-TEM tomography (Titan Krios) that will enable atomic and molecular structure research and three-dimensional subcellular and cellular imaging. The project will span all multiscale cryo-TEM modalities from the visualisation of cells, membranes and macromolecular complexes, through to near-atomic-resolution protein structure determination. Cryo-single particle analysis and tomography are recognised as revolutionary technologies in molecular structural biology and powerful enablers of future ground-breaking discovery. The project will deliver significant competitive advantage for Australia in leading-edge structure-based research, drug discovery, new opportunities for applied research and development, and showcasing science to the public.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0454170
Funder
Australian Research Council
Funding Amount
$187,341.00
Summary
Biacore3000-Expansion of Proteomics Facility. The sequencing of the human genome has led to redirection of effort towards the rapid characterisation of the products of genes, proteins. This project will establish state of the art facilities for protein identification and characterisation in the Hunter Region. The investigators are representative of several major research programs and are unified by their specific expertise in the fundamental molecular mechanisms underlying the control of cellula ....Biacore3000-Expansion of Proteomics Facility. The sequencing of the human genome has led to redirection of effort towards the rapid characterisation of the products of genes, proteins. This project will establish state of the art facilities for protein identification and characterisation in the Hunter Region. The investigators are representative of several major research programs and are unified by their specific expertise in the fundamental molecular mechanisms underlying the control of cellular processes in plants, animals and humans. Understanding these mechanisms will provide the basis for improved management of the environment and pathological conditions through identifying molecular targets for diagnosis, genetic manipulation or drug design.Read moreRead less
Molecular mechanisms of cyclic Adenosine Monophosphate (AMP) induced apoptosis. Cyclic Adenosine Monophosphate (cAMP) is an important cellular chemical necessary for cell growth. However, de-regulated cAMP production in response to altered physiology can result in cellular death or apoptosis. This is attributed to the development of certain human diseases and this project aims to understand the molecular mechanism behind this process.
Elucidating the regulation of cell death by random mutagenesis of key apoptotic proteins. All organisms need to remove damaged or excessive cells. This cell death process is called apoptosis. Defects in apoptosis result in numerous diseases including cancer, and neurodegenerative and immune disorders. Determining how this process is regulated is of crucial importance for therapeutic intervention. We will utilise a powerful strategy to mutate proteins required for apoptosis so that they no longer ....Elucidating the regulation of cell death by random mutagenesis of key apoptotic proteins. All organisms need to remove damaged or excessive cells. This cell death process is called apoptosis. Defects in apoptosis result in numerous diseases including cancer, and neurodegenerative and immune disorders. Determining how this process is regulated is of crucial importance for therapeutic intervention. We will utilise a powerful strategy to mutate proteins required for apoptosis so that they no longer work, which will allow the identification of protein regions essential for cell death activity . This will lead to identification of potential drug targets to control apoptosis. Elucidating the mechanism of cell death will lead to the development of novel and improved therapies for diseases such as cancer and neurodegenerative disease.Read moreRead less