Alpha-2-Macroglobulin And The Transport And Uptake Of The Hormone, Hepcidin
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
Hepcidin is a peptide hormone that is a major regulator of iron metabolism. It has been suggested that hepcidin is free in the blood. However, we recently identified that hepcidin binds with alpha-2-macroglobulin (a2-M) in the plasma and this increases the efficacy of this peptide. The demonstration that a2-M plays a role in hepcidin biology will lead to a better understanding of hepcidin physiology, the development of methods for its measurement and improved treatment of iron related diseases.
Discovery And Mechanisms Of Host Cell Factors In HIV Uncoating
Funder
National Health and Medical Research Council
Funding Amount
$635,098.00
Summary
HIV entry into the host cell involves release of its capsid, a protein shell protecting the viral genome. The capsid hijacks host proteins to cloak itself from cellular defenses while the cell has evolved sensors that can block viral infection. This proposal aims to discover proteins involved in this arms race between host and virus and decipher how they control capsid disassembly. This insight will help design new drugs against HIV infection and new ways to deliver genes for gene therapies.
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
Industrial Transformation Training Centres - Grant ID: IC230100046
Funder
Australian Research Council
Funding Amount
$5,000,000.00
Summary
ARC Training Centre for Radiochemical Technologies and Precision Radiopharmaceuticals. This project aims to train the next generation of radiochemists and discover new molecular approaches to harness radioactivity. Novel chemistry exploiting molecular incorporation of radioactive elements, stable chelation of metal radionuclides, bioconjugation methodologies, radioactivity capture via nanomaterials and cages, and the design of new peptidomimetic targeting molecules will deliver technological adv ....ARC Training Centre for Radiochemical Technologies and Precision Radiopharmaceuticals. This project aims to train the next generation of radiochemists and discover new molecular approaches to harness radioactivity. Novel chemistry exploiting molecular incorporation of radioactive elements, stable chelation of metal radionuclides, bioconjugation methodologies, radioactivity capture via nanomaterials and cages, and the design of new peptidomimetic targeting molecules will deliver technological advances to radiopharmaceutical science. Outcomes will include a highly-skilled workforce and enhanced commercial capacity to meet a rapidly escalating global radiopharmaceutical market. This project will provide significant benefits by securing an internal supply chain and know-how for cutting-edge radiochemical technologies.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
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