Molecular mechanisms of novel bacterial copper defense proteins. This project aims to reveal molecular and cellular mechanisms used by bacteria to neutralise the destructive effects of copper. Copper is an essential trace element in living systems. It is toxic to bacteria and so plays a vital role in nutritional immunity. To counteract copper toxicity, bacteria have evolved defense mechanisms. The project will investigate a novel but poorly understood class of bacterial proteins, the suppressor ....Molecular mechanisms of novel bacterial copper defense proteins. This project aims to reveal molecular and cellular mechanisms used by bacteria to neutralise the destructive effects of copper. Copper is an essential trace element in living systems. It is toxic to bacteria and so plays a vital role in nutritional immunity. To counteract copper toxicity, bacteria have evolved defense mechanisms. The project will investigate a novel but poorly understood class of bacterial proteins, the suppressor of copper sensitivity proteins, that contribute to this key virulence trait. The expected outcomes will be fundamental new knowledge of metallo-protein diversity, bacterial virulence mechanisms, and membrane protein function with potential impact on health, environment, and biotechnology.Read moreRead less
Structure and function of human zinc transporter membrane proteins. The aim of this project is to create fundamental new knowledge on how important mammalian membrane proteins operate. Membrane proteins are key drug targets and are significantly under-represented in structural databases. The project plans to combine innovative membrane protein screening technology with gene expression, structural biology, biophysics and cell biology. The project outcomes may elucidate specific molecular mechanis ....Structure and function of human zinc transporter membrane proteins. The aim of this project is to create fundamental new knowledge on how important mammalian membrane proteins operate. Membrane proteins are key drug targets and are significantly under-represented in structural databases. The project plans to combine innovative membrane protein screening technology with gene expression, structural biology, biophysics and cell biology. The project outcomes may elucidate specific molecular mechanisms underpinning the essential biological process of zinc homeostasis.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230101536
Funder
Australian Research Council
Funding Amount
$473,824.00
Summary
How does heme regulate blood vessel formation in the brain? There are more than 600 kilometres of blood vessels in the brain, all of which are lined by tightly packed cells that protect the brain from toxins. My research aims to investigate how these blood vessels are formed. This project expects to reveal the role that a critical signalling molecule called heme plays in this fundamental biological process. I will use cutting-edge structural biology and biophysical techniques to uncover the mole ....How does heme regulate blood vessel formation in the brain? There are more than 600 kilometres of blood vessels in the brain, all of which are lined by tightly packed cells that protect the brain from toxins. My research aims to investigate how these blood vessels are formed. This project expects to reveal the role that a critical signalling molecule called heme plays in this fundamental biological process. I will use cutting-edge structural biology and biophysical techniques to uncover the molecular mechanisms that allow heme to enter cells and regulate blood vessel growth in the brain. The outcomes of this research will enhance our understanding of the brain’s core infrastructure and will contribute to an understanding of how cerebral blood vessels grow and maintain integrity. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE150100149
Funder
Australian Research Council
Funding Amount
$590,000.00
Summary
Reaching new heights in high-resolution electron microscopy . High-resolution electron microscopy (EM): Direct electron detection cameras are a recent technological breakthrough delivering one of the greatest single advancements to the field of molecular cryo-EM. The aim of this project is to enable a 'first of a kind' cryo-EM platform in Australia enabling high-throughput atomic resolution protein structure determination. This will be achieved by integrating a state-of-the-art Gatan K2 Summit D ....Reaching new heights in high-resolution electron microscopy . High-resolution electron microscopy (EM): Direct electron detection cameras are a recent technological breakthrough delivering one of the greatest single advancements to the field of molecular cryo-EM. The aim of this project is to enable a 'first of a kind' cryo-EM platform in Australia enabling high-throughput atomic resolution protein structure determination. This will be achieved by integrating a state-of-the-art Gatan K2 Summit Direct Electron Detection camera system into the established cryo-EM facility managed by the University of Queensland node of the Australian Microscopy and Microanalysis Facility. This will offer unique and significantly improved capabilities for atomic resolution protein structure analysis, and will support a broad range of projects across the biological sciences.Read moreRead less
Comparing properties of innate immune proteins of bats and humans. Supra-molecular protein complexes known as signalosomes drive our innate immune response by forming large signaling hubs capable of recruiting downstream effectors. This project aims to compare the properties and structure of human and bat signalosomes and discover the molecular origins of the “supra-immunity” of bats. In this context, the project expects to generate new knowledge concerning the fundamental molecular mechanisms t ....Comparing properties of innate immune proteins of bats and humans. Supra-molecular protein complexes known as signalosomes drive our innate immune response by forming large signaling hubs capable of recruiting downstream effectors. This project aims to compare the properties and structure of human and bat signalosomes and discover the molecular origins of the “supra-immunity” of bats. In this context, the project expects to generate new knowledge concerning the fundamental molecular mechanisms that regulate the signalosomes. The intended outcome is to answer the long-standing question of control of speed and amplitude of innate immune response at the molecular level. Both locally and internationally, this new approach should provide benefits across structural biology, molecular evolution and biotechnology.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
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
Discovery Early Career Researcher Award - Grant ID: DE120102857
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Innovative chemical tools for the isolation, biochemical and structural analysis of biological macromolecular assemblies. This project will develop a new approach for determining the three dimensional structures of protein complexes. This project will demonstrate this approach by determining the structure of a protein complex involved in gene regulation and disease.
High-throughput microfluidic approach to mapping hierarchies of interactions in the gene regulation machinery. The exploration of protein-protein interactions networks is becoming an extremely active area of research in life sciences. The current project will develop new approaches to accelerate the discovery of novel interacting proteins participating in gene regulation, in order to understand how cells differentiate into different tissues and organs.