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
Harnessing molecular strain for drug discovery and bioconjugation. Peptides and proteins are increasingly important therapies for the treatment of disease. Nevertheless, the synthesis and optimisation of these high-value compounds still relies primarily on technologies developed decades ago. There is a desperate need for modern strategies to unlock the full potential of peptides and proteins for diverse applications in drug discovery. This interdisciplinary research aims to develop new tools for ....Harnessing molecular strain for drug discovery and bioconjugation. Peptides and proteins are increasingly important therapies for the treatment of disease. Nevertheless, the synthesis and optimisation of these high-value compounds still relies primarily on technologies developed decades ago. There is a desperate need for modern strategies to unlock the full potential of peptides and proteins for diverse applications in drug discovery. This interdisciplinary research aims to develop new tools for the construction and modification of peptides and proteins by harnessing the energy in a unique class of strained molecules. A focus on peptide-based inhibitors of the proteasome, a critical target for modern cancer treatments, should provide future health and economic benefits for the Australian community.Read moreRead less
Advances in Peptide Synthesis: Exploiting Underutilised Functional Groups. The translation of therapeutically-relevant classes of peptides to the clinic is often limited by chemists' ability to synthesise these complex biomolecules efficiently and sustainably. This project aims to develop new tools for the preparation of designer peptides that are broadly inspired by an underutilised reactive group found in naturally-occurring peptide sequences. Expected outcomes encompass health and economic be ....Advances in Peptide Synthesis: Exploiting Underutilised Functional Groups. The translation of therapeutically-relevant classes of peptides to the clinic is often limited by chemists' ability to synthesise these complex biomolecules efficiently and sustainably. This project aims to develop new tools for the preparation of designer peptides that are broadly inspired by an underutilised reactive group found in naturally-occurring peptide sequences. Expected outcomes encompass health and economic benefits for the Australian community, including: the first approach to a class of promising antibiotic peptide natural product analogues, the development of a mild electrochemical approach to peptide modification, and the production of a library of novel amino acids for incorporation into potential antibiotic leads.Read moreRead less