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New biocatalysts for selective chemical oxidations under extreme conditions. This project will identify and design new enzyme biocatalysts which function under extreme conditions such as elevated temperature and high concentrations of peroxides. These enzymes will be sourced from microorganisms which are located in extreme biological environments e.g. hot springs (the so-called extremophiles). The expected outcome of this project are the identification of robust enzymes which can catalyse select ....New biocatalysts for selective chemical oxidations under extreme conditions. This project will identify and design new enzyme biocatalysts which function under extreme conditions such as elevated temperature and high concentrations of peroxides. These enzymes will be sourced from microorganisms which are located in extreme biological environments e.g. hot springs (the so-called extremophiles). The expected outcome of this project are the identification of robust enzymes which can catalyse selective oxidation reactions in complex organic molecules, such as steroids. The new biocatalysts developed in this project will have significant benefit in the development of new routes to access bespoke molecules of value in fine chemical synthesis and drug development.
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Structure of the essential Commander protein trafficking complex. This project aims to provide a fundamental understanding of the structure and function of Commander, a large protein complex that controls export and recycling of internalised receptors. Commander is highly conserved throughout evolution and is essential for maintaining the homeostasis of hundreds of transmembrane receptors required for cell function and survival, regulating processes as diverse as lipid metabolism and cell adhesi ....Structure of the essential Commander protein trafficking complex. This project aims to provide a fundamental understanding of the structure and function of Commander, a large protein complex that controls export and recycling of internalised receptors. Commander is highly conserved throughout evolution and is essential for maintaining the homeostasis of hundreds of transmembrane receptors required for cell function and survival, regulating processes as diverse as lipid metabolism and cell adhesion. Despite advances in the understanding of Commander function, little is known about how Commander is assembled and interacts with other essential proteins. This project will use multidisciplinary cellular and structural biology approaches to reveal the architecture of Commander at an atomic level.Read moreRead less
All in the family: understanding a new class of bacterial toxins. This project aims to unravel missing molecular details of how a major superfamily of proteins is able to drill holes in cell membranes. Animals, plants, fungi and bacteria all use pore-forming proteins as cell-killing weapons of mass destruction. Despite their lethal nature and their roles in infection and immunity, how these proteins work remains enigmatic. The outcomes could reveal novel mechanisms general to these proteins and ....All in the family: understanding a new class of bacterial toxins. This project aims to unravel missing molecular details of how a major superfamily of proteins is able to drill holes in cell membranes. Animals, plants, fungi and bacteria all use pore-forming proteins as cell-killing weapons of mass destruction. Despite their lethal nature and their roles in infection and immunity, how these proteins work remains enigmatic. The outcomes could reveal novel mechanisms general to these proteins and provide fundamental insights in understanding vital physiological processes across all kingdoms of life. Ultimately, this knowledge may guide the design of artificial protein pores that are selective for specific molecules with applications such as measuring metal ions, sugars, pesticides or pollutants. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE240100135
Funder
Australian Research Council
Funding Amount
$880,000.00
Summary
An ion mobility-mass spectrometry based platform for structural proteomics. This project aims to establish a nationally unique facility dedicated to structural proteomics, combining high resolution ion mobility mass spectrometry with advanced separation, hydrogen/deuterium exchange and imaging platforms. Such technology is critical to characterise 3D biomacromolecular structures, dynamics, interactions and spatial location on a proteome-wide scale, and overcome current analytical limitations for ....An ion mobility-mass spectrometry based platform for structural proteomics. This project aims to establish a nationally unique facility dedicated to structural proteomics, combining high resolution ion mobility mass spectrometry with advanced separation, hydrogen/deuterium exchange and imaging platforms. Such technology is critical to characterise 3D biomacromolecular structures, dynamics, interactions and spatial location on a proteome-wide scale, and overcome current analytical limitations for structure determination from complex biological samples, particularly for closely related (isomeric) components. Servicing a diverse research community, this will enable new molecular insights to better understand the natural world, and accelerate cutting edge biotechnology advances intersecting life and chemical sciences.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240100931
Funder
Australian Research Council
Funding Amount
$453,237.00
Summary
Molecular insights into the allosteric regulation of opioid receptors. Allosteric regulation is the biological process by which molecules bind to proteins someplace other than their active site, regulating their activity. Proteins on the cell surface called membrane receptors can be allosterically regulated to fine-tune the response of cells to the environment. This project aims to investigate how small molecules regulate receptor activity at a molecular level, using opioid receptors as an exemp ....Molecular insights into the allosteric regulation of opioid receptors. Allosteric regulation is the biological process by which molecules bind to proteins someplace other than their active site, regulating their activity. Proteins on the cell surface called membrane receptors can be allosterically regulated to fine-tune the response of cells to the environment. This project aims to investigate how small molecules regulate receptor activity at a molecular level, using opioid receptors as an exemplar system. I will use an interdisciplinary approach that combines structural biology, medicinal chemistry, analytical pharmacology, and cell biology. The knowledge gained from these studies will advance fundamental understanding of receptor function and can lay the foundation for future drug discovery efforts.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230101284
Funder
Australian Research Council
Funding Amount
$397,003.00
Summary
Insect-specific virus host restriction. Mosquito-borne viruses are a topic of intense research due to their complex biology, ecology and evolution, and their potential to produce unpredictable outbreaks of disease in both humans and animals. Insect-specific viruses (ISVs) are viruses that replicate solely in mosquito cell and are unable to infect vertebrate tissues. This project aims to assess the biodiversity of ISVs in the Australian mosquito population and identify key factors behind their re ....Insect-specific virus host restriction. Mosquito-borne viruses are a topic of intense research due to their complex biology, ecology and evolution, and their potential to produce unpredictable outbreaks of disease in both humans and animals. Insect-specific viruses (ISVs) are viruses that replicate solely in mosquito cell and are unable to infect vertebrate tissues. This project aims to assess the biodiversity of ISVs in the Australian mosquito population and identify key factors behind their restriction in vertebrates. The objectives of the studies proposed will answer clearly defined important biological questions about ISVs, while also delivering technological advances, novel reagents and potential commercial outcomes for the control and prevention of arboviral disease. Read moreRead less
Beyond structure - solving conformational dynamics for intractable proteins. Proteins perform almost every task that enables the amazing complexity of cellular and whole organism physiology. These molecular machines perform this incredible array of tasks due to their ability to dynamically change shape. For the vast majority of these machines, we can only view a snapshot of the possible shapes they can adopt and can’t monitor how they change from one shape to another, which is critical for their ....Beyond structure - solving conformational dynamics for intractable proteins. Proteins perform almost every task that enables the amazing complexity of cellular and whole organism physiology. These molecular machines perform this incredible array of tasks due to their ability to dynamically change shape. For the vast majority of these machines, we can only view a snapshot of the possible shapes they can adopt and can’t monitor how they change from one shape to another, which is critical for their functioning. This project aims to develop and apply a completely new method to visualise dynamic changes in protein shape which is not possible with current techniques. This will allow us to provide a new description and understanding of the function of proteins, which is fundamental to all biology.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE240100054
Funder
Australian Research Council
Funding Amount
$1,341,398.00
Summary
Dedicated High-throughput 3D-Electron Diffractometer. This proposal aims to install the first dedicated high-throughput 3D-electron diffractometer in the Southern Hemisphere, and one of the first in the world. It will be able to rapidly solve the atomic-scale structures of molecules and materials for which this is now extremely difficult and time-consuming – or impossible – due to the inability to grow large enough crystals for traditional X-ray diffraction. It will thus provide a significant ad ....Dedicated High-throughput 3D-Electron Diffractometer. This proposal aims to install the first dedicated high-throughput 3D-electron diffractometer in the Southern Hemisphere, and one of the first in the world. It will be able to rapidly solve the atomic-scale structures of molecules and materials for which this is now extremely difficult and time-consuming – or impossible – due to the inability to grow large enough crystals for traditional X-ray diffraction. It will thus provide a significant advantage for chemists, physicists, biologists, geologists, and engineers who rely on detailed structural knowledge to rationally optimise the properties of their compounds, from pharmaceutical activity to carbon capture to superconductivity, to the substantial benefit of multiple national priority areas.Read moreRead less
The impact of copper on protein turnover. This project aims to elaborate a novel discovery by the research team, that a conserved copper-binding site in a group of conserved conjugating enzymes promotes ubiquitination of a range of essential proteins leading to their rapid degradation, which might be a means of maintaining copper homeostasis. This project will employ a range of integrated physicochemical, biochemical and cell biology approaches to illuminate the molecular nature of this copper a ....The impact of copper on protein turnover. This project aims to elaborate a novel discovery by the research team, that a conserved copper-binding site in a group of conserved conjugating enzymes promotes ubiquitination of a range of essential proteins leading to their rapid degradation, which might be a means of maintaining copper homeostasis. This project will employ a range of integrated physicochemical, biochemical and cell biology approaches to illuminate the molecular nature of this copper action on the enzyme and its partners. Expected outcomes include an analytical understanding of the molecular mechanisms of this process, and enhanced interdisciplinary collaboration between experts. Potential benefits include new strategies to intervene in copper-related disorders of aging.Read moreRead less