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
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: LE170100192
Funder
Australian Research Council
Funding Amount
$450,000.00
Summary
Deep Protein Sequencing, Structure and Quantification Facility. This project aims to establish state-of-the-art complementary mass spectrometers to help research into molecular structure and interactions, post-translational modifications, compound stability and availability within complex biological samples. The facility’s complementary mass spectrometers combine high specificity with high sensitivity and ultrafast scanning, and are expected to rapidly discover, identify and characterise biomole ....Deep Protein Sequencing, Structure and Quantification Facility. This project aims to establish state-of-the-art complementary mass spectrometers to help research into molecular structure and interactions, post-translational modifications, compound stability and availability within complex biological samples. The facility’s complementary mass spectrometers combine high specificity with high sensitivity and ultrafast scanning, and are expected to rapidly discover, identify and characterise biomolecules including peptides, proteins and small molecules. The discovery of unknown compounds is expected to improve fundamental understanding of molecular structure and function, provide opportunities for new bio-industries in health and the environment, and generate commercial opportunities through spin-off companies, patents and licensing.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100015
Funder
Australian Research Council
Funding Amount
$630,000.00
Summary
High-resolution and high-throughput Nuclear Magnetic Resonance (NMR) facility. This facility will provide researchers at James Cook University and The University of Queensland with a nuclear magnetic resonance spectroscope with a cryogenically cooled probe which will enable the structures of novel biomolecules from spiders, hookworms, plants and synthetic drugs to be revealed. These studies have the potential to lead to new drugs for cancer, pain, inflammatory and tropical diseases.
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
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
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.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE200100190
Funder
Australian Research Council
Funding Amount
$620,000.00
Summary
Electrophysiology Platform for Ion-channel Characterisation. Ion channels are ubiquitous pore-forming membrane proteins, with the human genome encoding >300 ion channels. The diverse roles of ion channels include action potential generation, control of ion flow across secretory and epithelial cells, and regulation of cell volume, motility and proliferation. Pharmacological modulators are powerful tools for probing ion channel function, but for most channels these tools are lacking. Thus, this p .... Electrophysiology Platform for Ion-channel Characterisation. Ion channels are ubiquitous pore-forming membrane proteins, with the human genome encoding >300 ion channels. The diverse roles of ion channels include action potential generation, control of ion flow across secretory and epithelial cells, and regulation of cell volume, motility and proliferation. Pharmacological modulators are powerful tools for probing ion channel function, but for most channels these tools are lacking. Thus, this project aims to develop the first comprehensive toolbox of ion channel modulators using an integrated in vitro/in vivo electrophysiology platform. These pharmacological tools will be made freely available to the Australian research community for probing the mechanism and physiological function of ion channels.Read moreRead less