Non-Canonical Amino Acids for Protein Analysis and Peptide Inhibitors. This interdisciplinary project aims to establish new tools to experimentally confirm 3D structure predictions of proteins that are otherwise difficult to study. A combination of innovative biochemistry, modern spectroscopy, and high-performance computing will be applied to study protein-protein and protein-ligand interactions. The project expects to generate new techniques and to test them on established drug targets. Expecte ....Non-Canonical Amino Acids for Protein Analysis and Peptide Inhibitors. This interdisciplinary project aims to establish new tools to experimentally confirm 3D structure predictions of proteins that are otherwise difficult to study. A combination of innovative biochemistry, modern spectroscopy, and high-performance computing will be applied to study protein-protein and protein-ligand interactions. The project expects to generate new techniques and to test them on established drug targets. Expected outcomes include new tools which quickly inform medicinal chemists how drugs interact with their targets and how they can be improved. The developed tools should provide significant benefit to many researchers by accelerating the early stage of drug discovery, and support Australia’s fast growing biotechnology sector.Read moreRead less
Protein Structure and Dynamics by Electron/Nuclear Paramagnetic Resonance. This interdisciplinary project aims to establish new magnetic resonance methods for the analysis of protein structure and motion at low concentrations and in physiological conditions that are otherwise difficult or impossible to study. It brings together four different research groups with expertise in advanced biochemistry, modern magnetic spectroscopy and high-performance computing. The project expects to develop tools ....Protein Structure and Dynamics by Electron/Nuclear Paramagnetic Resonance. This interdisciplinary project aims to establish new magnetic resonance methods for the analysis of protein structure and motion at low concentrations and in physiological conditions that are otherwise difficult or impossible to study. It brings together four different research groups with expertise in advanced biochemistry, modern magnetic spectroscopy and high-performance computing. The project expects to develop tools to study protein structure, protein-protein association and protein-ligand interactions of established drug-targets. Expected outcomes include new techniques that quickly inform how drugs work, providing significant benefits to many researchers studying biomolecules, and supporting Australia’s growing biotechnology sector. 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
The viral fusosome: a modular machinery for cargo delivery to target cells. The delivery of proteins, RNA and DNA into cells is a critical process in normal cellular biology, virus infection and biotechnology applications such as gene editing. Enveloped viruses achieve this maneuver with exquisite efficiency and specificity using a complex machinery mediating their fusion with cellular membranes for stealth genome delivery. Remarkably, all characterised viral fusion proteins belong to only 3 cla ....The viral fusosome: a modular machinery for cargo delivery to target cells. The delivery of proteins, RNA and DNA into cells is a critical process in normal cellular biology, virus infection and biotechnology applications such as gene editing. Enveloped viruses achieve this maneuver with exquisite efficiency and specificity using a complex machinery mediating their fusion with cellular membranes for stealth genome delivery. Remarkably, all characterised viral fusion proteins belong to only 3 classes defined >16 years ago and sharing surprisingly conserved mechanisms. We identified a novel class of fusion proteins with unique architecture in ubiquitous insect viruses. The Project will elucidate the structural and functional hallmarks of this fusion machinery providing a platform for its engineering.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230101681
Funder
Australian Research Council
Funding Amount
$457,139.00
Summary
Cryo-electron microscopy determination of G protein-coupled receptor states. This project aims to address fundamental knowledge gaps in understanding of the molecular mechanisms of peptide hormone G protein-coupled receptor activation. This will be achieved through cryo-electron microscopy determination of the structure and dynamics of key intermediate states in activation. Novel biochemical approaches will be applied to capture these states, using as exemplar the glucagon receptor that has a br ....Cryo-electron microscopy determination of G protein-coupled receptor states. This project aims to address fundamental knowledge gaps in understanding of the molecular mechanisms of peptide hormone G protein-coupled receptor activation. This will be achieved through cryo-electron microscopy determination of the structure and dynamics of key intermediate states in activation. Novel biochemical approaches will be applied to capture these states, using as exemplar the glucagon receptor that has a broad range of pharmacological tools to facilitate isolation of distinct functional states. The knowledge gained from these studies will advance fundamental understanding of physiologically important receptor activation and efficacy, while the approaches developed will enable similar investigation of other receptor classes.Read moreRead less
Elucidating the molecular mechanisms of dual function transporter/channels. This project aims to understand how a membrane protein that transports chemical messengers in the brain functions and how it is influenced by the membrane in which it is embedded. Cells from all life forms have a lipid membrane that separates them from their external environment. These membranes contain proteins that control the movements of molecules into and out of cells and are vital for a plethora of physiological pr ....Elucidating the molecular mechanisms of dual function transporter/channels. This project aims to understand how a membrane protein that transports chemical messengers in the brain functions and how it is influenced by the membrane in which it is embedded. Cells from all life forms have a lipid membrane that separates them from their external environment. These membranes contain proteins that control the movements of molecules into and out of cells and are vital for a plethora of physiological processes including cell-to-cell communication. The outcomes of this study will include new knowledge of this process and chemical modifiers of this transport protein. This project will benefit structural biology and biophysics training and may lead to the development of novel compounds that can be used to explore function. Read moreRead less
How does the chromatin remodeller CHD4 regulate gene expression? The mechanisms that determine how genes are switched on and off in different tissues and at different times are in many ways still mysterious. It is well established that gene expression patterns in complex organisms are determined in part by the manner in which DNA is physically packaged. Our aim is to define new aspects of these mechanisms that revolve around molecular motors that regulate DNA packaging. This foundational knowled ....How does the chromatin remodeller CHD4 regulate gene expression? The mechanisms that determine how genes are switched on and off in different tissues and at different times are in many ways still mysterious. It is well established that gene expression patterns in complex organisms are determined in part by the manner in which DNA is physically packaged. Our aim is to define new aspects of these mechanisms that revolve around molecular motors that regulate DNA packaging. This foundational knowledge will deepen our understanding of gene regulation in all complex organisms and will inform future efforts to rationally modulate gene expression patterns in agriculture, research and other important areas.Read moreRead less
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