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.
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
The effect of Pt binding to CTR1 on Cu homeostasis and cell phenotype. The copper transport protein CTR1 is commonly believed to transport active cisplatin (a platinum-based anticancer agent) into the cell, but this model is inconsistent with the chemical properties of platinum (Pt) and CTR1. The project aims to interrogate the interaction between CTR1 and Pt in cells by developing new chemical tools for the study of Pt species within cells. It will then study the effect of the CTR1-Pt interacti ....The effect of Pt binding to CTR1 on Cu homeostasis and cell phenotype. The copper transport protein CTR1 is commonly believed to transport active cisplatin (a platinum-based anticancer agent) into the cell, but this model is inconsistent with the chemical properties of platinum (Pt) and CTR1. The project aims to interrogate the interaction between CTR1 and Pt in cells by developing new chemical tools for the study of Pt species within cells. It will then study the effect of the CTR1-Pt interaction on copper homeostasis and cell phenotype. It is expected that the results will provide valuable information on the status of CTR1 and Pt following interaction, and reveal whether less toxic complexes are just as effective in decreasing cell malignancy as cisplatin itself.Read moreRead less
Dissecting the mitochondrial pathway of apoptotic cell death. This research aims to identify each step in cell death regulation by the Bcl-2 family of proteins. Each step is a potential target for drugs that may help cancer cells die, or that may help normal cells such as heart and brain cells recover from damage.
Total Synthesis of Myxobacteria Metabolites and Analogues. This project will investigate the total chemical synthesis of complex myxobacteria metabolites. In addition, the synthesis of new analogues of some of these natural products will also be investigated. The project endeavours to develop new methods for chemical synthesis and also to produce new therapeutic products which may possess greater efficacy and superior biological activities than the natural compounds. Most significantly, this pro ....Total Synthesis of Myxobacteria Metabolites and Analogues. This project will investigate the total chemical synthesis of complex myxobacteria metabolites. In addition, the synthesis of new analogues of some of these natural products will also be investigated. The project endeavours to develop new methods for chemical synthesis and also to produce new therapeutic products which may possess greater efficacy and superior biological activities than the natural compounds. Most significantly, this project will deliver natural and new compounds for analysis of anti-cancer activity. The rewards of the development of new synthetic methods are enormous for the community and in the education of our scientists.Read moreRead less
The development of tuneable materials to allow the three-dimensional printing of cells. New low cost three-dimensional (3D) printers and reagents will be developed during this project to allow cancer biologists to print cells and polymers as more realistic 3D tissue models for biological assays. Such technology will be important for performing basic research into cancers as well as for providing better tools for drug testing.
MRI Molecular Imaging Agents - from fundamental design to In Vivo Applications. Of approximately 60 million magnetic resonance imaging (MRI) procedures performed annually worldwide, around 30 per cent of these use MRI imaging agents. Imaging agents allow the doctors to study blood flow and to identify particular tissue types and diseases. This project will lead to new classes of high-performance imaging agents which offer the prospect of faster more accurate diagnosis.
Bioinks for the 3D printing of cells made from off-the-shelf components. This project aims to develop a simple method for creating complex, multiple-cell-type three-dimensional (3D) cell cultures for in-vitro cell based assays. Using 3D printing technology, this project will develop a versatile polymer system, made from entirely commercially available components, that gels upon printing and has functionality to assist cells in adhering, growing and migrating. The 3D printing of multiple cell typ ....Bioinks for the 3D printing of cells made from off-the-shelf components. This project aims to develop a simple method for creating complex, multiple-cell-type three-dimensional (3D) cell cultures for in-vitro cell based assays. Using 3D printing technology, this project will develop a versatile polymer system, made from entirely commercially available components, that gels upon printing and has functionality to assist cells in adhering, growing and migrating. The 3D printing of multiple cell types will provide biological scientists with more realistic in-vitro cell assays to those found in-vivo. Applications of the research are in cell biology, studying diseases and developing new drugs.Read moreRead less
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
Discovery Early Career Researcher Award - Grant ID: DE120101653
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Selective fluorination chemistry: a tool for creating bioactive, shape-controlled peptides. Fluorine atoms are desirable substituents in drug candidates because they can increase metabolic stability and hydrophobicity, and because they can be used to constrain molecules into optimal bioactive conformations. These concepts are being exploited to create shape-controlled peptides with applications in anti-cancer and anti-microbial therapy.