A new source of bivalent molecules from nature. This project aims to describe a new class of naturally occurring multivalent molecules termed secreted cysteine-rich repeat proteins (SCREPs). Multivalency is a key feature of molecular interaction in biology, underlying the high specificity and potency found in many proteins. Focusing on bivalent peptides, the project will generate a database of bioactive SCREPs with similarity to known bioactive peptides, and develop new recombinant methods for t ....A new source of bivalent molecules from nature. This project aims to describe a new class of naturally occurring multivalent molecules termed secreted cysteine-rich repeat proteins (SCREPs). Multivalency is a key feature of molecular interaction in biology, underlying the high specificity and potency found in many proteins. Focusing on bivalent peptides, the project will generate a database of bioactive SCREPs with similarity to known bioactive peptides, and develop new recombinant methods for their production. The project will use advanced nuclear magnetic resonance spectroscopy to characterise members of this new class, providing new insights into the design of bivalent and multivalent peptides and establishing a new source of molecules with applications in the rapidly growing biotechnology sector.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.
Australian Laureate Fellowships - Grant ID: FL150100146
Funder
Australian Research Council
Funding Amount
$2,977,310.00
Summary
Taking Australia from the farm to the pharm. Taking Australian from the farm to the pharm: This fellowship project aims to design novel drugs based on cyclic peptides that will be expressed in the seeds of plants to produce bio-pills — saving money for patients and the health care system. Plants produce unique cyclic peptides (mini-proteins) to protect themselves from pests and pathogens. This project aims to chemically redesign these peptides to produce stable protein-based pharmaceuticals that ....Taking Australia from the farm to the pharm. Taking Australian from the farm to the pharm: This fellowship project aims to design novel drugs based on cyclic peptides that will be expressed in the seeds of plants to produce bio-pills — saving money for patients and the health care system. Plants produce unique cyclic peptides (mini-proteins) to protect themselves from pests and pathogens. This project aims to chemically redesign these peptides to produce stable protein-based pharmaceuticals that can be eaten. It is hoped that these designer pharmaceuticals will be inexpensive, effective, easy to ingest and without the side effects of traditional drugs. The outcomes of this project are anticipated to be high-value drugs and agri-chemicals which will open up new high-value crops for Australian farmers and a new Australian ‘pharming’ industry.Read moreRead less
The chemistry and biology of circular proteins. This project aims to develop plant-derived ultra-stable cyclic peptides for pharmaceutical and agricultural applications. The project will use innovative new methodologies for discovery, chemical synthesis and engineering of these molecules. It is expected that the project will contribute to high value biotechnology and agricultural industries in Australia. The proposed outcomes will include fundamental new knowledge on the biosynthesis of circular ....The chemistry and biology of circular proteins. This project aims to develop plant-derived ultra-stable cyclic peptides for pharmaceutical and agricultural applications. The project will use innovative new methodologies for discovery, chemical synthesis and engineering of these molecules. It is expected that the project will contribute to high value biotechnology and agricultural industries in Australia. The proposed outcomes will include fundamental new knowledge on the biosynthesis of circular proteins in plants, new approaches for their discovery and technologies for applying them as drug leads and agricultural products.Read moreRead less
Voltage-dependent structural changes in voltage-gated sodium channels. This project aims to provide insights into the structural rearrangements experienced by Nav channels, which are key components of animal nervous systems. Voltage-gated sodium (Nav) channels initiate action potentials in excitable cells. They open in response to membrane depolarisation then rapidly inactivate. Eukaryotic Nav channels contain four unique voltage-sensor domains (VSDs) that control how the channel responds to mem ....Voltage-dependent structural changes in voltage-gated sodium channels. This project aims to provide insights into the structural rearrangements experienced by Nav channels, which are key components of animal nervous systems. Voltage-gated sodium (Nav) channels initiate action potentials in excitable cells. They open in response to membrane depolarisation then rapidly inactivate. Eukaryotic Nav channels contain four unique voltage-sensor domains (VSDs) that control how the channel responds to membrane potential changes. Recently reported crystal structures of bacterial Nav channels have greatly advanced the field, but these channels contain four identical VSDs and have different inactivation properties. Thus, much remains to be learnt about the conformational plasticity of eukaryotic Nav channel VSDs. The project plans to use animal toxins to capture eukaryotic VSDs in defined states of the gating cycle for detailed structural analysis using nuclear magnetic resonance and X-ray crystallography.Read moreRead less
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: DE160101142
Funder
Australian Research Council
Funding Amount
$360,000.00
Summary
Unravelling the structural evolution of centipede toxins. The project intends to improve understanding of venom evolution in centipedes, and uncover new families of peptides with potential application in the agrochemical and pharmaceutical sectors. Venoms have emerged as a rich source of pharmacological tools with potential for development into therapeutics and bioinsecticides. However, venoms-based discovery has been limited by the narrow taxonomical range studied, and many groups of venomous a ....Unravelling the structural evolution of centipede toxins. The project intends to improve understanding of venom evolution in centipedes, and uncover new families of peptides with potential application in the agrochemical and pharmaceutical sectors. Venoms have emerged as a rich source of pharmacological tools with potential for development into therapeutics and bioinsecticides. However, venoms-based discovery has been limited by the narrow taxonomical range studied, and many groups of venomous animals remain overlooked. One such group is centipedes, whose venoms contain diverse novel toxins. This project aims to provide an insight into centipede toxin evolution, and establish a structure-based approach to understanding their evolution and structural diversification. The outcomes may contribute to our understanding of protein evolution and support the development of new products.Read moreRead less
Understanding sub-cellular systems at the atomic level. By extending the range of biomolecular systems that can be modelled computationally at the atomic level the project will enable important biomedical processes such as how bacterial toxins penetrate cell membranes and how protein hormones transmit signals into cells to be understood in unprecedented detail.
ARC Centre of Excellence in Advanced Molecular Imaging. The Centre of Excellence in Advanced Molecular Imaging will innovatively integrate physics, chemistry and biology to unravel the complex molecular interactions that define immunity. The Centre will develop new imaging methods to visualize atomic, molecular and cellular details of how immune proteins interact and
effect immune responses. Outcomes: (i) new technological innovations leading to new imaging methods and products; and (ii) fundame ....ARC Centre of Excellence in Advanced Molecular Imaging. The Centre of Excellence in Advanced Molecular Imaging will innovatively integrate physics, chemistry and biology to unravel the complex molecular interactions that define immunity. The Centre will develop new imaging methods to visualize atomic, molecular and cellular details of how immune proteins interact and
effect immune responses. Outcomes: (i) new technological innovations leading to new imaging methods and products; and (ii) fundamental advances in understanding details of immune responses in health and disease. The Centre will enable Australia to be an international leader in biological imaging, to train next
generation interdisciplinary scientists, and to provide new insights for combating common diseases that afflict society.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100226
Funder
Australian Research Council
Funding Amount
$424,000.00
Summary
Advanced molecular discovery and characterisation facility. Natural product drug discovery in Australia requires access to high throughput functional assays to guide the separation and of novel bioactives with therapeutic potential. By establishing the advanced molecular discovery and characterisation facility in an academic environment across two institutions, research programs in early drug lead discovery and characterisation will be accelerated. It will provide unique capabilities not curren ....Advanced molecular discovery and characterisation facility. Natural product drug discovery in Australia requires access to high throughput functional assays to guide the separation and of novel bioactives with therapeutic potential. By establishing the advanced molecular discovery and characterisation facility in an academic environment across two institutions, research programs in early drug lead discovery and characterisation will be accelerated. It will provide unique capabilities not currently available in Australia, and help Australian researchers remain internationally competitive in breakthrough science and frontier technologies. The research enabled by this facility will lead to development of new drug candidates by the emerging Australian biotechnology industry.Read moreRead less