Discovery Early Career Researcher Award - Grant ID: DE180101165
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Structural insights into adenosine receptors. This project aims to investigate mechanisms underlying ligand binding and signal transduction at G protein-coupled receptors (GPCRs) by utilising the adenosine receptor family as a model system. This interdisciplinary project will use structural biology, pharmacology and biochemistry. The expected outcomes include understanding ligand selectivity across the four adenosine receptor family members. This should provide significant benefits, such as adva ....Structural insights into adenosine receptors. This project aims to investigate mechanisms underlying ligand binding and signal transduction at G protein-coupled receptors (GPCRs) by utilising the adenosine receptor family as a model system. This interdisciplinary project will use structural biology, pharmacology and biochemistry. The expected outcomes include understanding ligand selectivity across the four adenosine receptor family members. This should provide significant benefits, such as advancement of fundamental knowledge that could also lead to therapeutic development.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE200101511
Funder
Australian Research Council
Funding Amount
$424,816.00
Summary
Structural insights into activation, dynamics and bias of GPCRs. The project aims to investigate the mechanisms underlying activation, biased agonism and G protein selectivity of G protein-coupled receptors (GPCRs) by utilising the adenosine A1 receptor as a model system. This project expects to generate knowledge in the area of GPCR biology using an interdisciplinary approach including structural biology, pharmacology, biochemistry and protein engineering. The expected outcomes include (i) unde ....Structural insights into activation, dynamics and bias of GPCRs. The project aims to investigate the mechanisms underlying activation, biased agonism and G protein selectivity of G protein-coupled receptors (GPCRs) by utilising the adenosine A1 receptor as a model system. This project expects to generate knowledge in the area of GPCR biology using an interdisciplinary approach including structural biology, pharmacology, biochemistry and protein engineering. The expected outcomes include (i) understanding the structural mechanisms underlying GPCR activation, (ii) biased agonism and (iii) G protein selectivity. This should provide significant benefits, such as advancement of fundamental knowledge in GPCR biology and pharmacology that could also one day lead to therapeutic development.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.
Discovery Early Career Researcher Award - Grant ID: DE120101550
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Understanding multidrug resistance: identifying the molecular basis of substrate and inhibitor transport by P-glycoprotein. Chemotherapy resistance causes 90 per cent of cancer deaths and is commonly triggered by the increased activity of P-glycoprotein, which controls the cellular clearance of drugs. This project will determine how P-glycoprotein recognises and transports drugs, essential knowledge for the design of anticancer agents that can stop chemotherapy resistance.
Discovery Early Career Researcher Award - Grant ID: DE140101788
Funder
Australian Research Council
Funding Amount
$358,920.00
Summary
Structural Analysis of Biomolecular Complexes at Membrane Interfaces Important to Health and Disease. This project will study structural aspects of key biomolecular complexes at membrane interfaces that are involved with apoptosis (programmed cell death). Malfunctions in apoptosis have been implicated in many aliments including age-related diseases and cancers. Understanding of the molecular and structural aspects of key complexes can pave the way to novel therapies. The approach that will be us ....Structural Analysis of Biomolecular Complexes at Membrane Interfaces Important to Health and Disease. This project will study structural aspects of key biomolecular complexes at membrane interfaces that are involved with apoptosis (programmed cell death). Malfunctions in apoptosis have been implicated in many aliments including age-related diseases and cancers. Understanding of the molecular and structural aspects of key complexes can pave the way to novel therapies. The approach that will be used is to design new biomimetic outer mitochondrial membranes and use these to study the structure and binding of proteins involved with apoptosis. By studying simple models of complex systems, this project promises to yield detailed information on important biomolecular complexes where structural detail is currently lacking. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160100608
Funder
Australian Research Council
Funding Amount
$359,000.00
Summary
Investigating the structural basis of human antibody stability. This project plans to use protein engineering and X-ray crystallography to investigate the effects of stabilising mutations on antigen binding and the antibody-antigen interaction. Monoclonal antibodies are high-affinity reagents that have transformed the study of biological processes. However, antibodies often display inherent instability, which limits applicability. Mutations have recently been identified that render human antibod ....Investigating the structural basis of human antibody stability. This project plans to use protein engineering and X-ray crystallography to investigate the effects of stabilising mutations on antigen binding and the antibody-antigen interaction. Monoclonal antibodies are high-affinity reagents that have transformed the study of biological processes. However, antibodies often display inherent instability, which limits applicability. Mutations have recently been identified that render human antibodies resistant to aggregation. Preliminary data indicates that stabilising mutations improves the biophysical properties of monoclonals without affecting the native antibody structure. The project aims to provide detailed insights into the molecular basis of antibody stability.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE140100262
Funder
Australian Research Council
Funding Amount
$395,220.00
Summary
Artificial synthesis of bacteria's molecular syringe. The type III secretion system. The type III secretion system is an impressive protein superstructure consisting of hundreds of subunits that act cooperatively to specifically inject virulence factors directly into the cytoplasm of host cells. Its size and complexity make it a formidable challenge to understand at a molecular level with conventional methods. This project adopts a fundamentally new approach that will put Australian science in t ....Artificial synthesis of bacteria's molecular syringe. The type III secretion system. The type III secretion system is an impressive protein superstructure consisting of hundreds of subunits that act cooperatively to specifically inject virulence factors directly into the cytoplasm of host cells. Its size and complexity make it a formidable challenge to understand at a molecular level with conventional methods. This project adopts a fundamentally new approach that will put Australian science in the spotlight of a highly active research field. Artificial synthesis of bacteria's molecular syringe using DNA nanotechnology will revolutionise its study by providing unprecedented dexterity in its manipulation and, for the first time, allow the isolation of functional subcomplexes for high-resolution structural studies.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
Discovery Early Career Researcher Award - Grant ID: DE230101081
Funder
Australian Research Council
Funding Amount
$458,238.00
Summary
Developing CRISPR Prime Editing for highly efficient precise gene editing. This project will further develop a recent breakthrough in gene editing technology named CRISPR prime editing to improve its performance in generating specific genome modifications in cells and organisms. This project expects to generate new knowledge regarding optimal strategies for its deployment as well as create novel enhanced versions of the technology. This would significantly enhance our ability to perform precise ....Developing CRISPR Prime Editing for highly efficient precise gene editing. This project will further develop a recent breakthrough in gene editing technology named CRISPR prime editing to improve its performance in generating specific genome modifications in cells and organisms. This project expects to generate new knowledge regarding optimal strategies for its deployment as well as create novel enhanced versions of the technology. This would significantly enhance our ability to perform precise genome modification of organisms and lead to substantial benefits for a vast array of applications in fundamental and applied biology. Future applications will include generating mutations in cells and model organisms for basic research and creating genetically enhanced agricultural animals or plants.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160100893
Funder
Australian Research Council
Funding Amount
$364,000.00
Summary
How do effector proteins from necrotrophic fungi cause disease in plants? This project aims to develop new knowledge to support the development of strategies to protect wheat from necrotrophic fungi. Crop losses caused by plant diseases are a significant economic, environmental and social challenge in a world facing increased demands on food, fibre and biofuels. Parastagonospora nodorum is an economically important necrotrophic fungal pathogen of wheat. During infection, P. nodorum uses effector ....How do effector proteins from necrotrophic fungi cause disease in plants? This project aims to develop new knowledge to support the development of strategies to protect wheat from necrotrophic fungi. Crop losses caused by plant diseases are a significant economic, environmental and social challenge in a world facing increased demands on food, fibre and biofuels. Parastagonospora nodorum is an economically important necrotrophic fungal pathogen of wheat. During infection, P. nodorum uses effector proteins to target sensitivity gene products in wheat. This process, known as necrotrophic effector-triggered susceptibility, results in plant cell death and disease. This project aims to investigate the structural basis of necrotrophic effector-triggered susceptibility in the P. nodorum – wheat pathosystem.Read moreRead less