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Discovery Early Career Researcher Award - Grant ID: DE170100398
Funder
Australian Research Council
Funding Amount
$410,507.00
Summary
How T cells modulate stem cells and tissue regeneration. The project aims to determine how T cells modulate tissue repair and regeneration in mammals. Most of the mechanisms modulating the healing of tissues are elusive. This research is expected to reveal unknown mechanisms controlling the processes of tissue repair and regeneration, particularly the nexus between the stem cells involved in the tissue healing process and the immune response .
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
Discovery Early Career Researcher Award - Grant ID: DE240101233
Funder
Australian Research Council
Funding Amount
$447,237.00
Summary
Developing the toolbox of compounds that target acid-sensing proteins. This project aims to examine the interaction between acid-sensing proteins and their modulatory compounds. Animals, including humans, must sense changes in environmental acidity to successfully interact with the surrounding world. Expected outcomes of the project include a better understanding of which regions of these proteins detect acidity, and to develop new compounds that modulate the proteins’ function. This would advan ....Developing the toolbox of compounds that target acid-sensing proteins. This project aims to examine the interaction between acid-sensing proteins and their modulatory compounds. Animals, including humans, must sense changes in environmental acidity to successfully interact with the surrounding world. Expected outcomes of the project include a better understanding of which regions of these proteins detect acidity, and to develop new compounds that modulate the proteins’ function. This would advance our fundamental knowledge in the physiological process of acid sensing. This expects to provide significant benefits, by aiding the potential development of agrochemicals and pain-relieving medications that regulate acid-sensing protein function, resulting in economic benefit to Australia via these new products.
Read moreRead less
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: DE240100793
Funder
Australian Research Council
Funding Amount
$463,180.00
Summary
Unraveling a new cytokine working model in immune cell exhaustion. This project will investigate a novel paradigm of how a key messenger protein can be sensed by fundamental immune cells, preventing their ‘exhaustion’. Immune cell exhaustion is a fundamental mechanism to maintain the internal homeostasis of vertebrates. However, it is often hijacked by pathogens to dampen the defensive capacity of the immune system. And this specific messenger protein is the only known soluble factor that can d ....Unraveling a new cytokine working model in immune cell exhaustion. This project will investigate a novel paradigm of how a key messenger protein can be sensed by fundamental immune cells, preventing their ‘exhaustion’. Immune cell exhaustion is a fundamental mechanism to maintain the internal homeostasis of vertebrates. However, it is often hijacked by pathogens to dampen the defensive capacity of the immune system. And this specific messenger protein is the only known soluble factor that can deliver ‘anti-exhaustion’ signals to immune cells. This study will advance basic knowledge in biochemistry and immunology by combining interdisciplinary and cutting-edge approaches. The expected outcomes include the developing new scientific theories and identifying novel molecular basis of biological processes. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240101210
Funder
Australian Research Council
Funding Amount
$375,837.00
Summary
A liquid protein platform for dynamic bio-inspired reaction compartments. This project aims to investigate liquid protein as a novel material for biotechnology by producing protein droplets with a range of material and structural properties and assess the activity of internalised enzymes. The project will combine concepts from protein-based subcellular super-structure and enzyme protein structure and apply cutting-edge biochemistry methods to study how catalysis can be controlled and directed th ....A liquid protein platform for dynamic bio-inspired reaction compartments. This project aims to investigate liquid protein as a novel material for biotechnology by producing protein droplets with a range of material and structural properties and assess the activity of internalised enzymes. The project will combine concepts from protein-based subcellular super-structure and enzyme protein structure and apply cutting-edge biochemistry methods to study how catalysis can be controlled and directed through liquid protein design. Expected outcomes include a new platform for using protein droplets to engineer dynamic catalytic compartments, strong international and interdisciplinary collaborations, and a knowledge-base for building synthetic biology tools and technologies for future green chemistry-based industries.Read moreRead less