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Controlling the spatial distribution of targeting ligands on dendrimer surfaces as a means of dictating cellular recognition and fate. This project seeks to develop next generation targeted drug delivery systems that 'home' to specific target cells, including cancers. Targeted delivery systems have the potential to revolutionise therapy by providing bespoke drug distribution patterns that are tailored to specific diseases and result in enhanced activity and reduced toxicity.
Exploring metabotropic glutamate receptor 5 bias, allostery and heteromers. This project aims to provide novel mechanistic and structural insights into metabotropic glutamate receptor 5 (mGlu5) function. The mGlu5 is an essential regulator of neurotransmission and higher order brain functions including learning and memory. This project expects to expand knowledge of the fundamental biological processes engaged by mGlu5 through exploration of three novel paradigms of receptor activity: allostery, ....Exploring metabotropic glutamate receptor 5 bias, allostery and heteromers. This project aims to provide novel mechanistic and structural insights into metabotropic glutamate receptor 5 (mGlu5) function. The mGlu5 is an essential regulator of neurotransmission and higher order brain functions including learning and memory. This project expects to expand knowledge of the fundamental biological processes engaged by mGlu5 through exploration of three novel paradigms of receptor activity: allostery, bias and heteromerisation. Expected outcomes also include generation of new pharmacological tools through interdisciplinary collaborative research between multiple institutions. There is significant expected economic benefit through commercialisation of new tools and facilitation of novel drug discovery.Read moreRead less
Perturbation of the extracellular architecture to promote the absorption and lymphatic transport of biological macromolecules. Macromolecules therapeutics such as proteins, antibodies or polymer conjugates pose a number of pharmaceutical challenges. Where the dose is high, drainage of that dose from a subcutaneous injection site into the circulation, poses a particular problem. Here the project aims to explore how recombinant hyaluronidase, an enzyme that breaks down a structural component (hya ....Perturbation of the extracellular architecture to promote the absorption and lymphatic transport of biological macromolecules. Macromolecules therapeutics such as proteins, antibodies or polymer conjugates pose a number of pharmaceutical challenges. Where the dose is high, drainage of that dose from a subcutaneous injection site into the circulation, poses a particular problem. Here the project aims to explore how recombinant hyaluronidase, an enzyme that breaks down a structural component (hyaluronan) of the interstitum, can be used promote absorption into the draining blood and lymph capillaries. The project aims to also explore the downstream effects of hyaluronidase on lymph nodes and evaluate whether the enzyme is able to temporarily disrupt the lymph node structure and promote drug penetration into the lymph node mass. This has significant potential for improved drug targeting.Read moreRead less
Therapeutic approaches to treat human immunodeficiency virus infection: development of HIV-1 integrase inhibitors. This project aims to assist the development of new anti-HIV drugs, which would benefit the 15000 Australians and over 40 million people worldwide who are currently infected with this terrible disease. The project will utilise state of the art technologies - including the Australian Synchrotron when it is commissioned in 2007 - to identify and synthesise compounds as new leads for th ....Therapeutic approaches to treat human immunodeficiency virus infection: development of HIV-1 integrase inhibitors. This project aims to assist the development of new anti-HIV drugs, which would benefit the 15000 Australians and over 40 million people worldwide who are currently infected with this terrible disease. The project will utilise state of the art technologies - including the Australian Synchrotron when it is commissioned in 2007 - to identify and synthesise compounds as new leads for the treatment of HIV.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0560661
Funder
Australian Research Council
Funding Amount
$245,300.00
Summary
Particulate Characterisation for Pharmaceutical and Engineering Applications. The aim of this proposal is to establish joint facilities between the University of Sydney, Monash University and UNSW for the characterization of surface properties and particle sizes of pharmaceutical aerosols and industrial powders. Such knowledge is important for controlling aerosol production and delivery of drug particles to the lungs. This will have a significant benefit to the pharmaceutical industry and patien ....Particulate Characterisation for Pharmaceutical and Engineering Applications. The aim of this proposal is to establish joint facilities between the University of Sydney, Monash University and UNSW for the characterization of surface properties and particle sizes of pharmaceutical aerosols and industrial powders. Such knowledge is important for controlling aerosol production and delivery of drug particles to the lungs. This will have a significant benefit to the pharmaceutical industry and patients requiring aerosol treatment. Further, the proposed facilities will enhance research in complex particulate processes and modelling, functional nanomaterials, and soft sensor development, thus keeping Australia at the forefront of powder research into various high value adding particulate areas.Read moreRead less
DsbA: A target for the design of drug candidates as selective inhibitors of oxidative protein folding in Gram negative bacteria. There is a clear need for development of novel antibiotics which are capable of treating the increasingly prevalent strains of pathogenic bacteria that are resistant to currently available drugs. In this proposal we will design novel inhibitors of bacterial enzymes that are required for the correct folding of a variety of proteins and test the effects of these molecule ....DsbA: A target for the design of drug candidates as selective inhibitors of oxidative protein folding in Gram negative bacteria. There is a clear need for development of novel antibiotics which are capable of treating the increasingly prevalent strains of pathogenic bacteria that are resistant to currently available drugs. In this proposal we will design novel inhibitors of bacterial enzymes that are required for the correct folding of a variety of proteins and test the effects of these molecules on enzyme activity, bacterial growth and antibiotic resistance. Specific inhibitors of these enzymes constitute a novel strategy for the treatment of bacteria that have developed resistance to existing antimicrobial drugs.
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Supersaturated and non-digestible dispersions in the intestinal lumen: new mechanisms to reduce variability in the rate and extent of drug absorption. This project will design new polymers to be included in capsule formulations to prevent the precipitation of drugs in the intestine after their oral administration. This new technology will reduce the incidence of side-effects and ensure that patients absorb the correct dose of drug regardless of whether they take the drug before or after food.
Targeting virulence of Pseudomonas aeruginosa by inhibiting oxidative protein folding. Our research will lead to the development of compounds with a novel anti-virulence/antibacterial mode of action for further drug development.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775720
Funder
Australian Research Council
Funding Amount
$100,000.00
Summary
State-of-the-art high resolution thermal analysis suite for the life and material sciences. The facility, unique in Australia, will ensure that Australia will retains in a leading position in these research fields, will provide a basis to be competitive in international funding and support postgraduate training. The acquired equipments will strengthen the already existing infrastructures, enhancing understanding of intrinsic physico-chemical characteristic of various materials, to benefit the co ....State-of-the-art high resolution thermal analysis suite for the life and material sciences. The facility, unique in Australia, will ensure that Australia will retains in a leading position in these research fields, will provide a basis to be competitive in international funding and support postgraduate training. The acquired equipments will strengthen the already existing infrastructures, enhancing understanding of intrinsic physico-chemical characteristic of various materials, to benefit the community such as characterising functional nanomaterials for high-tech technologies and use of inhalation aerosol drug delivery to benefit patients with respiratory diseases for an improved therapeutic and health outcome.Read moreRead less
Regulation of large artery stiffness by endothelium-derived mediators and effects on the arterial pressure waveform. Stiffening of arteries is an important cardiovascular risk factor and increases with age, high blood pressure, high cholesterol and diabetes. Cells that line the blood vessels (endothelial cells), become damaged and this reduces the available amount of a dilator substance, nitric oxide, and increases the activity of a constrictor substance, endothelin-1. We have shown that nitric ....Regulation of large artery stiffness by endothelium-derived mediators and effects on the arterial pressure waveform. Stiffening of arteries is an important cardiovascular risk factor and increases with age, high blood pressure, high cholesterol and diabetes. Cells that line the blood vessels (endothelial cells), become damaged and this reduces the available amount of a dilator substance, nitric oxide, and increases the activity of a constrictor substance, endothelin-1. We have shown that nitric oxide regulates large artery stiffness and we believe that other endothelial mediators are also important regulators. Therefore, we aim to explore this in a series of studies. Regulation of stiffness of large arteries will improve treatment of age-related cardiovascular disease (eg isolated systolic hypertension)Read moreRead less