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Understanding the Chemical Processes Involved in the Metabolism of Peptide Hormones. Peptide hormones regulate normal physiological activity in humans, and their over-production causes diseases such as cancer. The aims of this project are: to delineate the chemical processes through which these hormones are produced; to develop inhibitors of enzymes involved in hormone production, and agonists and antagonists of receptors through which the hormones act; and to study the ability of the inhibitors ....Understanding the Chemical Processes Involved in the Metabolism of Peptide Hormones. Peptide hormones regulate normal physiological activity in humans, and their over-production causes diseases such as cancer. The aims of this project are: to delineate the chemical processes through which these hormones are produced; to develop inhibitors of enzymes involved in hormone production, and agonists and antagonists of receptors through which the hormones act; and to study the ability of the inhibitors, agonists and antagonists to override and bypass the chemical control mechanisms through which hormone levels are usually maintained at homeostasis. The research is expected to lead to a better fundamental understanding of hormone metabolism, and to underpin the basis for the development of new disease therapies.Read moreRead less
Sulfoxide Polymers - A New Paradigm in Polymer Design. Low fouling polymers are important for moderating interactions of molecules and particles with cells. In pharmaceutical sciences they are essential tools for extending the pharmacokinetics of dissolved drugs. However, the widely-used low-fouling polymer, poly(ethylene glycol) (PEG) has been recently reported to induce formation of anti-PEG antibodies. Polymeric alternatives to PEG are thus desperately needed. We introduce in this project sup ....Sulfoxide Polymers - A New Paradigm in Polymer Design. Low fouling polymers are important for moderating interactions of molecules and particles with cells. In pharmaceutical sciences they are essential tools for extending the pharmacokinetics of dissolved drugs. However, the widely-used low-fouling polymer, poly(ethylene glycol) (PEG) has been recently reported to induce formation of anti-PEG antibodies. Polymeric alternatives to PEG are thus desperately needed. We introduce in this project super-hydrophilic polymers incorporating sulfoxide groups, mimics of the polar solvent DMSO. The project aims to explore how polymer architecture can enhance biocompatibility and reduce biofouling. The outcome will be a new class of low-fouling polymeric materials with broad application in the biosciences.Read moreRead less
Heterologous expression of cyanobacterial compounds of analytical and therapeutic value. The project team has previously discovered the genetic basis for toxin production in cyanobacteria and algae. This project aims to define the biochemical pathways of the unique biosynthetic enzymes involved in alkaloid and cyclic peptide toxin production in these microorganisms. Via the development of large-gene cloning strategies, the toxins will be produced in a stable, sustainable and secure fermentation ....Heterologous expression of cyanobacterial compounds of analytical and therapeutic value. The project team has previously discovered the genetic basis for toxin production in cyanobacteria and algae. This project aims to define the biochemical pathways of the unique biosynthetic enzymes involved in alkaloid and cyclic peptide toxin production in these microorganisms. Via the development of large-gene cloning strategies, the toxins will be produced in a stable, sustainable and secure fermentation system. These compounds will be critical for standardising toxin detection methods in water supplies globally and for assessing their bioactivities in humans and other animals. Research students and the industry partner will also be trained to apply these novel biotechnologies for the production of other drug-like molecules.Read moreRead less
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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100050
Funder
Australian Research Council
Funding Amount
$744,100.00
Summary
New South Wales molecular analysis platform: Fourier transform ion cyclotron resonance mass spectrometer and CHN&S analyser. This project aims to provide critical infrastructure for research in the molecular sciences by providing state of the art mass spectrometry and elemental analysis instrumentation. The project will support research for over 100 groups in New South Wales (NSW) and will lead to new knowledge in a variety of areas. Expected outcomes include enhanced capacity and productivity, ....New South Wales molecular analysis platform: Fourier transform ion cyclotron resonance mass spectrometer and CHN&S analyser. This project aims to provide critical infrastructure for research in the molecular sciences by providing state of the art mass spectrometry and elemental analysis instrumentation. The project will support research for over 100 groups in New South Wales (NSW) and will lead to new knowledge in a variety of areas. Expected outcomes include enhanced capacity and productivity, new interdisciplinary collaborations and the discovery of novel materials and bioactive molecules, leading to wealth creation. The significant benefits of the NSW molecular analysis platform will include the ability to rapidly analyse molecules with the highest certainty, and will enhance the impact of Australian research via access to new technologies.Read moreRead less