Investigating The Link Between Oxidative Stress And Biomechanical Integrin Activation In Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$653,742.00
Summary
Diabetes represents a serious healthcare problem globally. A large proportion of deaths associated with diabetes can be attributed to the development of blood clots in the circulation of the heart and brain (heart attack/stroke). The blood clotting mechanism is ‘hyperactive’ in diabetes, although the reason for this is not well defined. In this proposal we will investigate a new mechanism promoting blood clots, and will investigate innovative approaches to reduce this clotting mechanism.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100170
Funder
Australian Research Council
Funding Amount
$580,000.00
Summary
Bioaffinity mass spectrometry infrastructure to identify small molecules binding to therapeutic targets. The development of anti-infective therapies is challenging because the underlying biology and biochemistry of pathogen virulence is not yet completely understood. This mass spectrometer facility will be used to identify small molecules suited for development into new therapies for malaria, tuberculosis and HIV.
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
Novel antimicrobial surface coatings for Cochlear implants. The objective of this project is to develop new antimicrobial coatings for materials used to manufacture biomedical devices. Infection associated with the use of biomaterials such as biomedical implants, catheters and orthopaedic prostheses is a major barrier to the use of these devices. The coatings that the project plans to develop are based on novel antimicrobials which have been shown to prevent adhesion and colonisation of biomater ....Novel antimicrobial surface coatings for Cochlear implants. The objective of this project is to develop new antimicrobial coatings for materials used to manufacture biomedical devices. Infection associated with the use of biomaterials such as biomedical implants, catheters and orthopaedic prostheses is a major barrier to the use of these devices. The coatings that the project plans to develop are based on novel antimicrobials which have been shown to prevent adhesion and colonisation of biomaterials by bacteria in vivo. This strategy has the potential to prevent device-related infections and revolutionise the biomaterials industry.Read moreRead less
Evaluation Of Molecular Mechanisms Driving Metastasis Using Integrated Intravital Imaging
Funder
National Health and Medical Research Council
Funding Amount
$885,271.00
Summary
Metastasis is the leading cause of cancer-associated death. Understanding key steps that drive the spread of cancer is critical to improve current treatment strategies. Using cutting-edge imaging technology and 3-dimensional model systems that mimic the disease, we will pinpoint key events that are susceptible to drug intervention and identify new therapeutic targets.
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
Biomolecular surface interactions with smart biomaterials. Current materials used for medical implants are often recognised by the body as foreign materials causing implant rejection or encapsulation. Research into the interactions between biological molecules and chemically and topographically modified materials will aid in the development of new materials and devices that optimise the body's response to the implanted material. The new materials and surfaces developed from this research will pr ....Biomolecular surface interactions with smart biomaterials. Current materials used for medical implants are often recognised by the body as foreign materials causing implant rejection or encapsulation. Research into the interactions between biological molecules and chemically and topographically modified materials will aid in the development of new materials and devices that optimise the body's response to the implanted material. The new materials and surfaces developed from this research will provide longer lasting implants and reduce the need for repeated operations. This will improve the quality of life for implant recipients and reduce health care costs.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