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
Diene regenerative Diels-Alder reactions to access chemical scaffolds. This project aims to develop methods and strategies that allow rapid access to biologically active chemical scaffolds based on natural products. Natural products and their analogues are vital starting points for drug discovery as they provide unique chemical diversity. Without efficient methods for their production, it is not possible to exploit this diversity. This project will develop an efficient, modular strategy that wil ....Diene regenerative Diels-Alder reactions to access chemical scaffolds. This project aims to develop methods and strategies that allow rapid access to biologically active chemical scaffolds based on natural products. Natural products and their analogues are vital starting points for drug discovery as they provide unique chemical diversity. Without efficient methods for their production, it is not possible to exploit this diversity. This project will develop an efficient, modular strategy that will allow the preparation of a wide range of chemicals in a timely manner. Restoring access to potent biologically active materials is expected to generate chemical probes and lead to molecules that could have biomedical value.Read moreRead less
New strategies for the stereoselective synthesis of Stemona alkaloids and the discovery of new bioactive molecules. The project aims to develop innovative methods to prepare bioactive natural products and their analogues with potential applications as new and safer therapeutic drugs and agricultural chemicals. These products would be of benefit to Australians in the future.
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
Fluorescent sensing of the intracellular redox environment. This project aims to develop chemical approaches to measure the redox environment of living cells. Oxidation and reduction (redox) reactions are crucial for cellular health and disease and the redox status of cells is known to affect their response to external stress, but surprisingly there remains no way of efficiently and accurately determining cellular redox environments. In this project, new fluorescent redox sensors will be designe ....Fluorescent sensing of the intracellular redox environment. This project aims to develop chemical approaches to measure the redox environment of living cells. Oxidation and reduction (redox) reactions are crucial for cellular health and disease and the redox status of cells is known to affect their response to external stress, but surprisingly there remains no way of efficiently and accurately determining cellular redox environments. In this project, new fluorescent redox sensors will be designed and incorporated into assays that enable high-throughput analysis of cell types. These fundamental chemical and biochemical studies could provide the basis of future research into how redox environment can be used as a predictor for disease and therapeutic outcomes.Read moreRead less
Novel peptide mimics for the disruption of chemical communication in bacteria. It is now well established that bacteria communicate with each other via small diffusible signalling molecules and coordinate their activities such as biofilm formation, swarming and expression of virulence factors in a coordinated manner. This project will investigate the synthesis of novel organic molecules that have the capacity to disrupt chemical communication in bacteria. This could allow control of the unwante ....Novel peptide mimics for the disruption of chemical communication in bacteria. It is now well established that bacteria communicate with each other via small diffusible signalling molecules and coordinate their activities such as biofilm formation, swarming and expression of virulence factors in a coordinated manner. This project will investigate the synthesis of novel organic molecules that have the capacity to disrupt chemical communication in bacteria. This could allow control of the unwanted microbial activity without the use of growth inhibitory agents such as antibiotics, preservatives and disinfectants that select for the resistant organisms. This elegant approach to eradicating the virulence behaviour of microbes represents a novel strategy to combat antimicrobial resistance.Read moreRead less
New methods for the chemical synthesis of a library of glycopeptide-based tri-component cancer vaccines. A novel method for the synthesis of tumour-associated glycopeptides will be developed in this research as well as the preparation of a library of glycopeptide-based cancer vaccines. These vaccines will be tested in immunological studies with a view to elucidating new immune-based therapies for the treatment of cancer.
New scaffolds for antimicrobial discovery. This project aims to investigate the synthesis of novel glyoxylamide antimicrobial peptide mimics that have the capacity to disrupt bacterial membranes. The innovative interdisciplinary approach expects to generate new, small molecular antimicrobial mimics that possess a low propensity for developing resistance. This could allow control of the unwanted microbial activity without the use of antibiotics that select for the resistant organisms. It will pro ....New scaffolds for antimicrobial discovery. This project aims to investigate the synthesis of novel glyoxylamide antimicrobial peptide mimics that have the capacity to disrupt bacterial membranes. The innovative interdisciplinary approach expects to generate new, small molecular antimicrobial mimics that possess a low propensity for developing resistance. This could allow control of the unwanted microbial activity without the use of antibiotics that select for the resistant organisms. It will provide excellent training for young researchers and lead to high quality research publications in international journals.Read moreRead less
Molecular Interactions with an antibiotic target in DNA replication. This project aims to develop and use new technologies to address mechanistic aspects of anti-bacterial compounds in development, and of the development of resistance to them. The project will focus on the sliding clamp subunit of the bacterial replicative polymerase by studying its association with many other proteins in vitro and in vivo, using novel techniques in solid-state NMR, single-molecule fluorescence and molecular mic ....Molecular Interactions with an antibiotic target in DNA replication. This project aims to develop and use new technologies to address mechanistic aspects of anti-bacterial compounds in development, and of the development of resistance to them. The project will focus on the sliding clamp subunit of the bacterial replicative polymerase by studying its association with many other proteins in vitro and in vivo, using novel techniques in solid-state NMR, single-molecule fluorescence and molecular microbiology. The outcomes are expected to be an increased understanding of bacterial DNA replication and mechanisms of antibiotic action and resistance. This project expects to generate new knowledge to assist in combatting antibiotic resistance in Gram-negative bacterial pathogens.Read moreRead less
The development of carboranes as new agents in the diagnosis and treatment of brain disease. The treatment of brain diseases is one of society's major challenges. To address these challenges, we need a better understanding of the molecular mechanisms involved in brain disease. This project will develop innovative agents to probe disease progression, assess efficacy of treatment, and ultimately treat a wide range of brain disorders.