Investigating the functional interaction between vasopressin and angiotensin receptors. Kidney disease resulting from diabetes is a major health issue for Australians, and indigenous Australians in particular. This project aims to enable improved therapies to be developed, as well as better inform doctors regarding the use of potential combinations of existing pharmaceuticals to treat this condition.
Understanding the Cellular Pathways of Nuclear Receptor Activation. The success of drug treatment depends critically on specificity, i.e., stimulation of a therapeutic response at a target site, and avoidance of activity at other (potentially toxic) locations. This project aims to explore how drug interactions with binding proteins in the cytosol can induce nuclear transport and tissue specific activation of nuclear receptors - a major drug target. The project intends to employ molecular, struct ....Understanding the Cellular Pathways of Nuclear Receptor Activation. The success of drug treatment depends critically on specificity, i.e., stimulation of a therapeutic response at a target site, and avoidance of activity at other (potentially toxic) locations. This project aims to explore how drug interactions with binding proteins in the cytosol can induce nuclear transport and tissue specific activation of nuclear receptors - a major drug target. The project intends to employ molecular, structural and cell biology approaches to map drug-binding protein-receptor interactions and to determine how the structure of these complexes dictates receptor activation. The data could provide a roadmap to design drugs that interact with the right protein in the right tissue and in doing so dramatically enhance drug specificity.Read moreRead less
Treating tuberculosis: targeted delivery of multidrug nano-suspensions. Tuberculosis (TB) is a lung disease of worldwide prevalence. Treatment times are long and mortality is high in children and the elderly. Current treatments are ineffective and drug resistant TB is a real pandemic threat. The project will develop a cost-effective nano-particle system that can be incorporated into conventional nebulisers for use worldwide.
CHARGED LIPOSACCHARIDE BASED DRUG DELIVERY SYSTEM. Complexation of a drug with lipid and/or sugar units represents one of the most important of the strategies being investigated in this burgeoning field. Increasing the lipid solubility of a hydrophilic compound has been established as an important factor in improving its absorption as it is necessary for passive transport across intestinal mucosal membranes. The role of sugar unit is very important: (i) it modifies the physico-chemical propertie ....CHARGED LIPOSACCHARIDE BASED DRUG DELIVERY SYSTEM. Complexation of a drug with lipid and/or sugar units represents one of the most important of the strategies being investigated in this burgeoning field. Increasing the lipid solubility of a hydrophilic compound has been established as an important factor in improving its absorption as it is necessary for passive transport across intestinal mucosal membranes. The role of sugar unit is very important: (i) it modifies the physico-chemical properties (solubility), (ii) utilizes active transport systems (e.g. Glucose transport) and (iii) target the compound - "MAGIC BULET" (Lewis X analogues - damaged cells). There is no limit to the areas of medicine and public health that would benefit from revolutionary new technology in these areas.Read moreRead less
Functional Materials to Hijack on Lipid Transport Pathways. This Project aims to provide new design rules for novel polymers with lipid elements that would allow them to interact with natural lipid trafficking pathways in precise ways.
The anticipated goal is to generate a greater understanding on how these materials co-opt lipid transport pathways, serum albumins and lipoprotein nanoparticle assemblies, as a function of lipid component, molecular weight and macromolecular structure.
Expected ....Functional Materials to Hijack on Lipid Transport Pathways. This Project aims to provide new design rules for novel polymers with lipid elements that would allow them to interact with natural lipid trafficking pathways in precise ways.
The anticipated goal is to generate a greater understanding on how these materials co-opt lipid transport pathways, serum albumins and lipoprotein nanoparticle assemblies, as a function of lipid component, molecular weight and macromolecular structure.
Expected outcomes of this project may be novel lipid functional materials with tuneable pharmokinetics, plasma exposure, lymph exposure and biodistribution. These materials would have wide application in the pharmaceutical and veterinary industries.Read moreRead less
Determinants of Expression, Assembly and Function of the Noradrenaline Transporter. The noradrenaline transporter protein that is the focus of this project is important for mental health because it belongs to the family of proteins where psychostimulants, such as cocaine, and drugs used in the treatment of depression act. The project will lead to exciting advances in our understanding of how the structure of this protein controls its functions, and potentially to the design of better antidepress ....Determinants of Expression, Assembly and Function of the Noradrenaline Transporter. The noradrenaline transporter protein that is the focus of this project is important for mental health because it belongs to the family of proteins where psychostimulants, such as cocaine, and drugs used in the treatment of depression act. The project will lead to exciting advances in our understanding of how the structure of this protein controls its functions, and potentially to the design of better antidepressant drugs and to the design of drugs to prevent the effects of cocaine.Read moreRead less
Discovering novel allosteric probes of muscarinic acetylcholine receptors. This project aims at fostering novel approaches to selectively target vital receptors in the human body, the muscarinic acetylcholine receptors (mAChRs). By harnessing the design of receptor mutations, compounds synthesis and fluorescent imaging, the project expects to develop new pharmacological tools for a family of receptors essential for the life of all vertebrates. By enriching our understanding of this family of rec ....Discovering novel allosteric probes of muscarinic acetylcholine receptors. This project aims at fostering novel approaches to selectively target vital receptors in the human body, the muscarinic acetylcholine receptors (mAChRs). By harnessing the design of receptor mutations, compounds synthesis and fluorescent imaging, the project expects to develop new pharmacological tools for a family of receptors essential for the life of all vertebrates. By enriching our understanding of this family of receptor, the project expects to provide significant benefits to the research field by impacting on future drug discovery efforts, not only at mAChRs, but at other structurally related receptors.Read moreRead less
Enabling aerosol delivery of phages to defeat antibiotic-resistant bacteria. This project aims to explore the use of bacteriophages towards producing a safe, natural, and highly effective alternative to traditional antibiotics. Respiratory infections caused by multidrug-resistant Gram-negative bacteria are a major health problem worldwide, and cost Australia over $150 million annually. Some 5,000 Australians die each year from antibiotic resistant infections. The project aims to produce efficac ....Enabling aerosol delivery of phages to defeat antibiotic-resistant bacteria. This project aims to explore the use of bacteriophages towards producing a safe, natural, and highly effective alternative to traditional antibiotics. Respiratory infections caused by multidrug-resistant Gram-negative bacteria are a major health problem worldwide, and cost Australia over $150 million annually. Some 5,000 Australians die each year from antibiotic resistant infections. The project aims to produce efficacious and stable formulations of bacteriophages for easy delivery by inhalation as aerosols with a long shelf-life, making them a commercially viable product. The expected research outcome can lead to an economic and efficient technology to produce phage powders for novel treatment strategies of infections by inhalation.Read moreRead less
Synthetic derivatives of capsaicin and gingerols as analgesics acting at the vanilloid receptor. This project aims to prepare alpha-hydroxyketones and gingerol derivatives acting at vanilloid (VR1) receptor with potential analgesic activity. These compounds will be tested for their ability to activate the VR1 receptor, desensitize the receptor and release neuropeptides associated with pain pathways. The development of these novel compounds will contribute towards understanding the mechanisms of ....Synthetic derivatives of capsaicin and gingerols as analgesics acting at the vanilloid receptor. This project aims to prepare alpha-hydroxyketones and gingerol derivatives acting at vanilloid (VR1) receptor with potential analgesic activity. These compounds will be tested for their ability to activate the VR1 receptor, desensitize the receptor and release neuropeptides associated with pain pathways. The development of these novel compounds will contribute towards understanding the mechanisms of VR1 receptor activation and provide information on how the VR1 receptor is regulated. We will determine and compare neurotoxicity of these compounds to capsaicin which is known to possess neurotoxic activity. The outcome of this project may result in effective agents for better pain management.
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Engineering of co-crystal drug molecules for pharmaceutical aerosols. This project will enable Australia to become a world leader in treatment of respiratory diseases. The Australian financial burden of respiratory diseases is currently estimated as $900m with significant impact on infrastructure (through regular clinical visits, hospitalisation and workforce loss). The global market for the treatment of COPD is currently $32 billion and is expected to increase significantly by 2010. The positio ....Engineering of co-crystal drug molecules for pharmaceutical aerosols. This project will enable Australia to become a world leader in treatment of respiratory diseases. The Australian financial burden of respiratory diseases is currently estimated as $900m with significant impact on infrastructure (through regular clinical visits, hospitalisation and workforce loss). The global market for the treatment of COPD is currently $32 billion and is expected to increase significantly by 2010. The positioning of an Australian research as a world leader in the development of new treatments will have significant national benefit, whilst the sector will benefit for scientific advancements that arise during this project.Read moreRead less