Pharmacology Of Potential Anti-Tumour Agents: Iron Chelators Of The BpT Class
Funder
National Health and Medical Research Council
Funding Amount
$585,455.00
Summary
Pharmacology of Potential Anti-Tumour Agents: Iron Chelators of the BpT Class Cancer cells have a high iron requirement for DNA synthesis and many clinical trials showed Fe chelators are effective anti-cancer drugs. Their potential to act as anti-tumour agents has been confirmed by the entrance of Triapine into widespread NCI clinical trials. In this NHMRC Renewal, we will perform pharmacological and preclinical studies to promote the development of BpT chelators as novel anti-tumour agents.
Discovery and characterisation of novel spider-venom peptides targeting the human sodium ion channel Nav1.7. Drugs that selectively block the human sodium ion channel Nav1.7 are likely to be powerful analgesics for treating a wide variety of pain conditions. However, it has proved difficult to obtain selective blockers of this channel. The aim of this project is to determine whether spider-venoms might provide a source of highly selective Nav1.7 blockers.
Discovery and applications of circular proteins. The many national benefits that will flow from this program include (i) new knowledge in plant biochemistry, peptide chemistry and protein engineering protected by a strong intellectual property position that will give Australia a competitive edge in relevant biotechnology applications; (ii) the training of a new generation of skilled researchers to drive a sustainable biotechnology sector in Australia; (iii) economic benefits from royalty returns ....Discovery and applications of circular proteins. The many national benefits that will flow from this program include (i) new knowledge in plant biochemistry, peptide chemistry and protein engineering protected by a strong intellectual property position that will give Australia a competitive edge in relevant biotechnology applications; (ii) the training of a new generation of skilled researchers to drive a sustainable biotechnology sector in Australia; (iii) economic benefits from royalty returns on drugs and agricultural products that will likely arise from the program; (iv) environment benefits due to a reduced need for chemical insecticides; and (v) social benefits due to a reduction in suffering from diseases for which drugs are developed as a result of this program.Read moreRead less
Novel strategies in the design and development of antivirals against dengue virus. Globally, there are 50-100 million cases of dengue fever, with 500,000 cases of the more severe dengue haemorrhagic fever, each year. Australia has between 100 and 900 cases of dengue infection annually, often from travellers, but disease outbreaks occur in northern Australia. Effective anti-viral treatment will reduce disease burden. The project contributes to an evidence-based drug design program in collaboratio ....Novel strategies in the design and development of antivirals against dengue virus. Globally, there are 50-100 million cases of dengue fever, with 500,000 cases of the more severe dengue haemorrhagic fever, each year. Australia has between 100 and 900 cases of dengue infection annually, often from travellers, but disease outbreaks occur in northern Australia. Effective anti-viral treatment will reduce disease burden. The project contributes to an evidence-based drug design program in collaboration with Australia's leading biotechnology industries. As a biotechnology industry project developing treatments for an emerging disease, it contributes to the national research priorities of Frontier technologies for building and transforming Australian industries, Promoting and maintaining good health and Safeguarding Australia.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989759
Funder
Australian Research Council
Funding Amount
$360,000.00
Summary
Australian Access to and Operation of Advanced Synchrotron Radiation Facilities at the Photon Factory. The primary national benefit of this application will be continued access by peer review for Australian scientists to the advanced synchrotron-radiation capabilities of the Australian National Beamline Facility and other complementary beamlines at the Photon Factory, Japan. This proposal is consistent with the National Research Priorities of An Environmentally Sustainable Australia, Promoting a ....Australian Access to and Operation of Advanced Synchrotron Radiation Facilities at the Photon Factory. The primary national benefit of this application will be continued access by peer review for Australian scientists to the advanced synchrotron-radiation capabilities of the Australian National Beamline Facility and other complementary beamlines at the Photon Factory, Japan. This proposal is consistent with the National Research Priorities of An Environmentally Sustainable Australia, Promoting and Maintaining Good Health and Frontier Technologies for Building and Transforming Australian Industries and will generate science to support and stimulate domestic industry, enhance the domestic knowledge base and international research profile, train students and future synchrotron scientists and foster domestic and international collaborations.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
Selectively targeting cancer and infectious disease with fragment-based drug discovery. Finding better compounds as starting points is one of the major challenges for drug discovery research. Fragments are small, weak binding molecules that can be upsized into drug leads with better properties when compared to starting with larger molecules. This project addresses two weaknesses of current fragment based drug discovery (FBDD) methods: first, the limitations associated with screening fragments; a ....Selectively targeting cancer and infectious disease with fragment-based drug discovery. Finding better compounds as starting points is one of the major challenges for drug discovery research. Fragments are small, weak binding molecules that can be upsized into drug leads with better properties when compared to starting with larger molecules. This project addresses two weaknesses of current fragment based drug discovery (FBDD) methods: first, the limitations associated with screening fragments; and second, the quality of commercial fragment libraries. This project anticipates that the findings will establish a commanding role for both mass spectrometry and three-dimensional fragments in advancing FBDD approaches. It also expects to identify fragments with favourable development prospects towards the next generation of therapeutics.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100092
Funder
Australian Research Council
Funding Amount
$418,107.00
Summary
A radical approach to unnatural amino acids and peptide-based antibiotics. This project aims to develop a new synthetic approach to valuable amino acid derivatives and their rapid incorporation into peptide analogues, including promising new antibiotic candidates. This project expects to generate knowledge in the chemical and biological sciences and build scientific capacity to address the global rise of antimicrobial resistance. It is anticipated that this will provide direct health and economi ....A radical approach to unnatural amino acids and peptide-based antibiotics. This project aims to develop a new synthetic approach to valuable amino acid derivatives and their rapid incorporation into peptide analogues, including promising new antibiotic candidates. This project expects to generate knowledge in the chemical and biological sciences and build scientific capacity to address the global rise of antimicrobial resistance. It is anticipated that this will provide direct health and economic benefits by establishing a powerful platform for peptide drug design.Read moreRead less
Development of potent and specific modulators of the human sodium channel Nav1.7. There are few effective drugs available for the treatment of chronic pain. This team recently discovered that spider venoms are a rich source of inhibitors of Nav1.7, a new target for anti-pain drugs. The goal of this project is to develop potent blockers of Nav1.7 that can be used to critically assess the role of this ion channel in mediating pain.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE170100075
Funder
Australian Research Council
Funding Amount
$315,000.00
Summary
Acoustic liquid handling robotics for bioactive compound discovery. This project aims to use a Labcyte Echo 550 acoustic dispenser with Combination Software to deliver sophisticated assay-ready screening. The Echo is the only liquid handling dispenser for 1536-well microplates and will allow Australian researchers to develop assay miniaturisation. The robotics will provide our nation’s researchers with a distinct competitive edge by enhancing assay sophistication, accuracy and reproducibility wh ....Acoustic liquid handling robotics for bioactive compound discovery. This project aims to use a Labcyte Echo 550 acoustic dispenser with Combination Software to deliver sophisticated assay-ready screening. The Echo is the only liquid handling dispenser for 1536-well microplates and will allow Australian researchers to develop assay miniaturisation. The robotics will provide our nation’s researchers with a distinct competitive edge by enhancing assay sophistication, accuracy and reproducibility while reducing cost. The expected benefits will advance the elucidation of molecular mechanisms involved in complex biological phenomena. The benefits of this are substantial, including reduction in test compound and reagents, which in turn reduces laboratory costs, conserves cells and increases data quality.Read moreRead less