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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
Hitting bacteria with a Bam: Lectin-Like Antimicrobials as New Antibiotics. Antibiotic resistance in disease-causing bacteria is a rapidly growing problem, making the development of new antibiotics of critical importance. This project aims to develop naturally produced lectin-like protein antibiotics as novel antimicrobial agents. To achieve this, the project will produce an extensive library of these antibiotics and test them for potency and specificity. Using cutting-edge techniques, it will d ....Hitting bacteria with a Bam: Lectin-Like Antimicrobials as New Antibiotics. Antibiotic resistance in disease-causing bacteria is a rapidly growing problem, making the development of new antibiotics of critical importance. This project aims to develop naturally produced lectin-like protein antibiotics as novel antimicrobial agents. To achieve this, the project will produce an extensive library of these antibiotics and test them for potency and specificity. Using cutting-edge techniques, it will determine how these antibiotics kill cells on a molecular and cellular level. It is anticipated this research will create the tools and knowledge required to exploit lectin-like protein antibiotics to fight bacterial infection, which will lead to their use in the prevention of crop and livestock losses due to disease.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
Nanopore sensors for multiplexed, ultra-fast gene detection. The aim of this research is to develop the application of protein nanopores for multiplex identification of DNA samples for ultrafast gene detection. This is a type of barcoding of organism DNA that allows for rapid gene identification. This technology aims to address a significant need for rapid, on-the-spot identification of organisms. Applications include rapid identification of pathogenic bacteria in infections and identification o ....Nanopore sensors for multiplexed, ultra-fast gene detection. The aim of this research is to develop the application of protein nanopores for multiplex identification of DNA samples for ultrafast gene detection. This is a type of barcoding of organism DNA that allows for rapid gene identification. This technology aims to address a significant need for rapid, on-the-spot identification of organisms. Applications include rapid identification of pathogenic bacteria in infections and identification of organisms in environmental sampling. Current methods are relative slow, require DNA amplification and specialised laboratories.
This proposal aims to fine tune the properties of the large nanopore, polyC9, with respect to size and charge, as well as to identify and characterise novel large nanopores. 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
Human Leukocyte Antigen-A and -B regulation of Natural Killer cell function. The aim of this project is to determine how genetic variation in the genes encoding cell surface receptors expressed by innate lymphocytes and the molecules they recognise diversifies their capacity to sense and respond to infection. This knowledge is critical for understanding why there are intrinsic differences between individuals with respect to their capacity to respond to different types of infection and will ultim ....Human Leukocyte Antigen-A and -B regulation of Natural Killer cell function. The aim of this project is to determine how genetic variation in the genes encoding cell surface receptors expressed by innate lymphocytes and the molecules they recognise diversifies their capacity to sense and respond to infection. This knowledge is critical for understanding why there are intrinsic differences between individuals with respect to their capacity to respond to different types of infection and will ultimately inform our capacity to better deploy personalised medicines.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