Enzyme-Mediated Machining of Chelators to Bind and Recover Valuable Metals. Metals are critical components of electronic devices and electrical products. Rapid disposal cycles create a major problem in managing e-waste metals and identifies an opportunity in the circular economy for recovery and re-use. Organic compounds that bind metal ions (chelators) are useful but could be improved to select a target metal from a mixture. This project aims to dissect a method used by bacteria to biosynthesiz ....Enzyme-Mediated Machining of Chelators to Bind and Recover Valuable Metals. Metals are critical components of electronic devices and electrical products. Rapid disposal cycles create a major problem in managing e-waste metals and identifies an opportunity in the circular economy for recovery and re-use. Organic compounds that bind metal ions (chelators) are useful but could be improved to select a target metal from a mixture. This project aims to dissect a method used by bacteria to biosynthesize chelators and hijack this to bioengineer new classes of chelators. Outcomes include new chelators and advanced knowledge of metal selectivity, with potential environmental and economic benefits arising from recovery of valuable metals. The project will benefit chemical biology research training for real-world applications.Read moreRead less
Development Of Small Molecules For The Treament Of Colon Cancer
Funder
National Health and Medical Research Council
Funding Amount
$684,379.00
Summary
Colon cancer remains one of the leading causes of cancer related deaths in Australia and in the developed world. Despite improvements in prevention and therapies, there remains a considerable need for efficacious therapeutic options. We have identified a lead compound inhibiting the growth of cancer cells. We will progress this series further toward clinical trials and aim to provide patients with a new orally available molecule with potent activity against colon cancer.
Mixing the jigsaw pieces of natural products: new molecules-new properties. This project aims to examine the capacity of exploiting the bacterial biosynthetic machinery to fast-track access to analogues of natural products. Due to increased drug resistance, new reservoirs of natural products are needed for evaluation as future drugs. Desferrioxamine B will be used as a model natural product to establish the biosynthesis of new analogues in bacterial culture supplemented with unsaturated, fluorin ....Mixing the jigsaw pieces of natural products: new molecules-new properties. This project aims to examine the capacity of exploiting the bacterial biosynthetic machinery to fast-track access to analogues of natural products. Due to increased drug resistance, new reservoirs of natural products are needed for evaluation as future drugs. Desferrioxamine B will be used as a model natural product to establish the biosynthesis of new analogues in bacterial culture supplemented with unsaturated, fluorinated or deuterated building blocks. The intended outcomes are to deliver advances in methods for generating structurally diverse pools of natural products, new label-free probes, knowledge of natural product biosynthesis, and excellence in training research students in frontier methods in chemical biology and drug discovery.Read moreRead less
Improving the function of GABA-A receptors is a key property of several classes of clinically important drugs including benzodiazepines and many anticonvulsants. However, the binding sites and molecular mechanisms of these drugs remain poorly understood. Using compounds similar to those in green tea, we will determine the molecular mechanism of these drugs. This understanding will lead to the development of better drugs for treatment of anxiety, depression, epilepsy, insomnia & schizophrenia.
Discovery Early Career Researcher Award - Grant ID: DE130101650
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Rational design of novel metal-based chaperones for tumour-selective drug delivery. This work aims to develop new drug delivery systems based on transition metal complexes for selective delivery and release of a drug in the tumour.
Supercharging antioxidant capacity. This project aims to deliver improved, tailor-made antioxidants that can better protect key biomolecules and other materials against collateral damage from oxidants within cells. Through fundamental chemistry research, this project aims to understand the relationship between antioxidant capacity and molecular structure, and, through computational chemistry, develop a predictive tool. This, in turn, will provide the means to design molecules that better protect ....Supercharging antioxidant capacity. This project aims to deliver improved, tailor-made antioxidants that can better protect key biomolecules and other materials against collateral damage from oxidants within cells. Through fundamental chemistry research, this project aims to understand the relationship between antioxidant capacity and molecular structure, and, through computational chemistry, develop a predictive tool. This, in turn, will provide the means to design molecules that better protect against oxidative processes. The expected outcome is improved technology to heal tissue damage and inflammation caused by enzymes.Read moreRead less
Engineered Hydroxamic Acids for Zirconium-89 Positron Emission Tomography (PET) Imaging of Prostate Cancer. Positron emission tomography (PET) using a zirconium-89-ligand complex bound to a prostate-specific membrane antigen is used to detect and monitor prostate cancer. The hydroxamic acid-based ligand bound to zirconium has a high affinity towards iron, which can cause metal exchange in vivo and loss of radiotracer. The project will prepare new ligands with a higher specificity towards zirconi ....Engineered Hydroxamic Acids for Zirconium-89 Positron Emission Tomography (PET) Imaging of Prostate Cancer. Positron emission tomography (PET) using a zirconium-89-ligand complex bound to a prostate-specific membrane antigen is used to detect and monitor prostate cancer. The hydroxamic acid-based ligand bound to zirconium has a high affinity towards iron, which can cause metal exchange in vivo and loss of radiotracer. The project will prepare new ligands with a higher specificity towards zirconium over iron, and measure immuno-PET imaging activity. A second series of macrocyclic zirconium-specific ligands will be prepared to establish the relationship between variable water-lipid solubility and pharmacokinetic properties. The results will increase the capability of immuno-PET for prostate cancer detection and improve survival outcomes.Read moreRead less
Escaping Bio-Assay Guided Isolation: Nature's Tools for Chemical Biology. The project aims to transform the approach to identify novel biologically active compounds that occur in nature. For decades, natural product chemistry has centred on bio-assay guided isolation, but it has become increasingly difficult to isolate novel compounds. While de-replication strategies detect the presence of known compounds using databases, more impact would be achieved by directly detecting novel compounds. Nucle ....Escaping Bio-Assay Guided Isolation: Nature's Tools for Chemical Biology. The project aims to transform the approach to identify novel biologically active compounds that occur in nature. For decades, natural product chemistry has centred on bio-assay guided isolation, but it has become increasingly difficult to isolate novel compounds. While de-replication strategies detect the presence of known compounds using databases, more impact would be achieved by directly detecting novel compounds. Nuclear magnetic resonance (NMR) spectroscopy detects every molecule that has a proton and is quantitative. This project plans to develop a NMR technique to escape bio-assay guided isolation by analysing a fraction library. Biotechnology innovation is dependent on novel compounds to provide new products. Replacing ‘grind and find’ with a technique that never lies would be transformational.Read moreRead less
Antimicrobial and anti-Leishmanial bismuth compounds and materials. The project aims to develop the bioinorganic and medicinal chemistry of bismuth and related metals to address two global health issues: parasitic infections (principally Leishmaniasis) and antibacterial resistance. Through targeting serious microbial infections, the project will research the chemical, physical, structural and biological properties of bismuth and related metals. The project will form bio-protective materials and ....Antimicrobial and anti-Leishmanial bismuth compounds and materials. The project aims to develop the bioinorganic and medicinal chemistry of bismuth and related metals to address two global health issues: parasitic infections (principally Leishmaniasis) and antibacterial resistance. Through targeting serious microbial infections, the project will research the chemical, physical, structural and biological properties of bismuth and related metals. The project will form bio-protective materials and surfaces through incorporating bismuth and its compounds into polymer matrices. It will establish the complexes’ chemical biology and toxicology through scrutinising cellular mechanisms, particularly modern metallomic techniques. New compounds developed may address the urgent and significant health issue of antibiotic resistance and help address poorly treated parasitic infections.Read moreRead less
Biogenesis inspired total synthesis of natural products. The project will study the chemical synthesis of a number of novel natural products. Most significantly, this project will deliver new methods for organic synthesis of complex molecules. The rewards from the total synthesis of bioactive compounds are enormous for the community and in the education and training of scientists.