Praziquantel: a unique pharmaceutical challenge. Generating effective and affordable drugs for the treatment of tropical diseases is a huge public health challenge. We will pioneer an open source approach to collaborative research in drug discovery. We aim to discover an inexpensive route to an important pharmaceutical so that it can be greatly improved and distributed to the affected populations for a realistic price. Success in this project will improve the lives of millions of sufferers of th ....Praziquantel: a unique pharmaceutical challenge. Generating effective and affordable drugs for the treatment of tropical diseases is a huge public health challenge. We will pioneer an open source approach to collaborative research in drug discovery. We aim to discover an inexpensive route to an important pharmaceutical so that it can be greatly improved and distributed to the affected populations for a realistic price. Success in this project will improve the lives of millions of sufferers of this disease, and demonstrate a new way of doing research on drugs for related diseases such as malaria. Read moreRead less
Total Synthesis of the Microsclerodermins: Anti-fungal Cyclic Peptides. Fungal infections are one of the major causes of morbidity and mortality in the increasing immunocompromised patient population, which includes AIDS, chemotherapy and organ transplant patients. The aim of this project is to discover new anti-fungal treatments for drug-resistant pathogenic fungal infections, based on the microsclerodermin family of natural products. The small quantity of microsclerodermin isolated from the na ....Total Synthesis of the Microsclerodermins: Anti-fungal Cyclic Peptides. Fungal infections are one of the major causes of morbidity and mortality in the increasing immunocompromised patient population, which includes AIDS, chemotherapy and organ transplant patients. The aim of this project is to discover new anti-fungal treatments for drug-resistant pathogenic fungal infections, based on the microsclerodermin family of natural products. The small quantity of microsclerodermin isolated from the natural environment hampers the development of anti-fungal agents from this natural product. Innovative synthetic methods will be developed to prepare large quantities of microsclerodermins and related compounds for biological testing, thereby furthering the development of this promising class of anti-fungal drugs.Read moreRead less
Design and Development of HIV-1 Integrase Inhibitors Based on a Natural Product Lead. HIV/AIDS is a significant health problem with over 40 million people infected with HIV worldwide. Resistance to current drugs is rising rapidly and new therapeutics are urgently needed. This project will bring together local expertise in organic synthesis and virology in order to develop new and better treatments for HIV/AIDS. Ultimately, Australians with HIV may benefit directly from anti-HIV compounds produce ....Design and Development of HIV-1 Integrase Inhibitors Based on a Natural Product Lead. HIV/AIDS is a significant health problem with over 40 million people infected with HIV worldwide. Resistance to current drugs is rising rapidly and new therapeutics are urgently needed. This project will bring together local expertise in organic synthesis and virology in order to develop new and better treatments for HIV/AIDS. Ultimately, Australians with HIV may benefit directly from anti-HIV compounds produced and may also benefit from advances in our understanding of this elusive virus resulting from the project.Read moreRead less
Structural determination of respiratory membrane protein complexes by X-ray crystallography. Membrane proteins form only 0.3% of the available protein structures in the protein data bank (PDB), yet 30% of the proteins in the human genome and 50% of human drug targets are membrane proteins. We have managed to increase the success rate through rational screening and development of new crystallization screens, with downstream implications for basic and medical research. Results from this proposal w ....Structural determination of respiratory membrane protein complexes by X-ray crystallography. Membrane proteins form only 0.3% of the available protein structures in the protein data bank (PDB), yet 30% of the proteins in the human genome and 50% of human drug targets are membrane proteins. We have managed to increase the success rate through rational screening and development of new crystallization screens, with downstream implications for basic and medical research. Results from this proposal will receive international recognition and will encourage more research in this field, attracting international funding, and create new research opportunities. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100087
Funder
Australian Research Council
Funding Amount
$450,000.00
Summary
Regional Facility for Molecular Characterisation and Mapping. Researchers at the Schools of Chemistry at The Australian National University and University of Wollongong are involved in a range of projects where new molecules are synthesised or discovered in natural products such as rainforest plants and marine organisms. Some of the molecules have already shown promise against diseases such as Alzheimer's and cardiovascular disease. In order to fully characterise these molecules, two complementa ....Regional Facility for Molecular Characterisation and Mapping. Researchers at the Schools of Chemistry at The Australian National University and University of Wollongong are involved in a range of projects where new molecules are synthesised or discovered in natural products such as rainforest plants and marine organisms. Some of the molecules have already shown promise against diseases such as Alzheimer's and cardiovascular disease. In order to fully characterise these molecules, two complementary mass spectrometers, replacing ageing instrumentation will be commissioned at each site. In addition, researchers in Wollongong will acquire a MALDI mass spectrometer capable of imaging the distribution of molecules on tissues that may be pathologically important.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100010
Funder
Australian Research Council
Funding Amount
$720,000.00
Summary
A 5-D Correlative Imaging Platform: Combining the strengths of light and electron microscopy. This will be Australia's first dedicated five-dimensional multiphoton-microscopy platform, allowing observation of dynamic structures across different length and time scales under controlled temperatures, followed by high-resolution electron microscopy studies on the same samples. This platform will provide a unique characterisation tool to Australia's top-flight investigators, and so contribute to the ....A 5-D Correlative Imaging Platform: Combining the strengths of light and electron microscopy. This will be Australia's first dedicated five-dimensional multiphoton-microscopy platform, allowing observation of dynamic structures across different length and time scales under controlled temperatures, followed by high-resolution electron microscopy studies on the same samples. This platform will provide a unique characterisation tool to Australia's top-flight investigators, and so contribute to the nation's research priorities. It will enable: fundamental studies of cancer, neural diseases and immune disorders; the development of frontier technologies, such as smart nanomaterials, biosensors and targeted drug delivery; and applied research to help plants and soils adapt to climate variability, and to increase sustainable use of water.Read moreRead less
Free Radicals in Chemistry and Biology: A Computational Quantum Chemistry Investigation. This proposal aims to carry out state-of-the-art chemistry research using computers rather than traditional laboratory techniques. Free radicals, which have widespread importance in the multibillion dollar polymer and health industries, form the centrepiece of the proposal. These are highly reactive substances that are difficult to study by conventional experimental techniques but ideal to study using compu ....Free Radicals in Chemistry and Biology: A Computational Quantum Chemistry Investigation. This proposal aims to carry out state-of-the-art chemistry research using computers rather than traditional laboratory techniques. Free radicals, which have widespread importance in the multibillion dollar polymer and health industries, form the centrepiece of the proposal. These are highly reactive substances that are difficult to study by conventional experimental techniques but ideal to study using computers. The increased understanding of free radicals that will stem from this research may help in dealing with ageing, and afflictions such as hardening of the arteries and vitamin B12 deficiency. It will also result in the training at the highest level of new generations of chemists in this exciting field of "chemistry with computers".Read moreRead less
Computational Quantum Chemistry Study of Molecular Structures, Stabilities and Reactions. Computational quantum chemistry is revolutionizing the study and practice of chemistry. We will use state-of-the-art computer calculations to investigate chemical structures, stabilities and reactions, particularly for free radicals. Radicals are of great importance in chemistry, biology and polymer science, but are difficult to study experimentally. We will use the computer calculations to determine how ....Computational Quantum Chemistry Study of Molecular Structures, Stabilities and Reactions. Computational quantum chemistry is revolutionizing the study and practice of chemistry. We will use state-of-the-art computer calculations to investigate chemical structures, stabilities and reactions, particularly for free radicals. Radicals are of great importance in chemistry, biology and polymer science, but are difficult to study experimentally. We will use the computer calculations to determine how to make radicals more stable, how they react to produce polymers, how they cause damage to proteins, and how they are involved in helping vitamin B12 make reactions go faster. We will create new methodologies in order to reliably achieve these goals.Read moreRead less
Mechanisms and consequences of oxidation of glycosaminoglycans, proteins and proteoglycans by myeloperoxidase-derived oxidants. Atherosclerosis (hardening of the arteries) is responsible for the death of 40% of the population of developed, and developing, countries including Australia. Rupture of the fibrous cap of atherosclerotic lesions is responsible for most sudden deaths from heart disease and stokes, but is a poorly understood process. Evidence has been presented for a role for oxidation r ....Mechanisms and consequences of oxidation of glycosaminoglycans, proteins and proteoglycans by myeloperoxidase-derived oxidants. Atherosclerosis (hardening of the arteries) is responsible for the death of 40% of the population of developed, and developing, countries including Australia. Rupture of the fibrous cap of atherosclerotic lesions is responsible for most sudden deaths from heart disease and stokes, but is a poorly understood process. Evidence has been presented for a role for oxidation reactions in weakening the structure of lesions and making them prone to rupture. Little is known about the fundamental chemistry of such damage; this will be addressed in the proposed program. The data obtained will underpin the development of new preventative and protective strategies to minimise lesion rupture and deaths from this major disease.Read moreRead less
Cross-linked Tyrosine Residues in Peptides and Proteins. Many peptides and proteins have recently been found to contain unusual structural modifications, commonly in the form of cross-linked tyrosine residues. The aims of this project are to design and synthesise examples of these cross-linked tyrosine structures, thereby enabling the preparation of models of the modified proteins. Outcomes of this research will include an increased understanding of the relationship between the three-dimensional ....Cross-linked Tyrosine Residues in Peptides and Proteins. Many peptides and proteins have recently been found to contain unusual structural modifications, commonly in the form of cross-linked tyrosine residues. The aims of this project are to design and synthesise examples of these cross-linked tyrosine structures, thereby enabling the preparation of models of the modified proteins. Outcomes of this research will include an increased understanding of the relationship between the three-dimensional structure and biological activity of peptides/proteins, the generation of lead compounds for new anti-bacterial and anti-fungal pharmaceuticals, and the preparation of biological 'markers' of the processes involved in neurodegenerative diseases and aging.Read moreRead less