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
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.
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
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.
Development of prodrug strategies for achieving increased penetration and selective activation in solid tumours. A primary cause of cancer deaths is relapse following treatment resulting from the drug failing to penetrate and destroy all parts of the tumour. The project aims to develop anticancer agents that are better able to reach all parts of the tumour and have toxicities low enough to enable sufficient doses to be used to kill all cancer cells.
A platform for the efficient optimisation of drug delivery using cross-linked micelles and thioclick-chemistry toward better anti-cancer treatment. The delivery of albendazole - an anti-cancer drug - will be improved by encapsulating the drug into nanoparticles. State of the art polymer chemistry will be employed to generate a versatile drug delivery system. The resulting nanoparticles will be able to better control drug delivery and to enhance cellular uptake of the drug.
Discovery Early Career Researcher Award - Grant ID: DE140101788
Funder
Australian Research Council
Funding Amount
$358,920.00
Summary
Structural Analysis of Biomolecular Complexes at Membrane Interfaces Important to Health and Disease. This project will study structural aspects of key biomolecular complexes at membrane interfaces that are involved with apoptosis (programmed cell death). Malfunctions in apoptosis have been implicated in many aliments including age-related diseases and cancers. Understanding of the molecular and structural aspects of key complexes can pave the way to novel therapies. The approach that will be us ....Structural Analysis of Biomolecular Complexes at Membrane Interfaces Important to Health and Disease. This project will study structural aspects of key biomolecular complexes at membrane interfaces that are involved with apoptosis (programmed cell death). Malfunctions in apoptosis have been implicated in many aliments including age-related diseases and cancers. Understanding of the molecular and structural aspects of key complexes can pave the way to novel therapies. The approach that will be used is to design new biomimetic outer mitochondrial membranes and use these to study the structure and binding of proteins involved with apoptosis. By studying simple models of complex systems, this project promises to yield detailed information on important biomolecular complexes where structural detail is currently lacking. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE150101518
Funder
Australian Research Council
Funding Amount
$345,000.00
Summary
Cellular responses to nanoparticles from cells on micropatterned surfaces. The mechanisms underlying cell-nanoparticle interactions remain largely unknown. It has hampered the design and development of innovative nano devices to be used for drug delivery, biomarkers and diagnostics. This project aims to explore the influences of cell size, density, geometry, intercellular communication and substrate properties on cell-nanoparticle interactions. A micropatterning technology is applied to precisel ....Cellular responses to nanoparticles from cells on micropatterned surfaces. The mechanisms underlying cell-nanoparticle interactions remain largely unknown. It has hampered the design and development of innovative nano devices to be used for drug delivery, biomarkers and diagnostics. This project aims to explore the influences of cell size, density, geometry, intercellular communication and substrate properties on cell-nanoparticle interactions. A micropatterning technology is applied to precisely control cell behaviour and provide a novel in vitro cellular model for nanoparticle studies. This project aims to significantly improve the understanding of cell-nanoparticle interactions to provide new insight into nanoparticle design and improve the efficacy of nano devices.Read moreRead less