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Nanoengineering materials to combat antimicrobial resistance. This project aims to understand how nanoengineered materials can be designed to kill bacteria and fungi without causing antimicrobial resistance. Resistance to antimicrobial drugs already leads to many thousands of deaths annually and costs society billions of dollars. Nanomaterials have unique abilities to attack microbes in multiple ways that could limit resistance. This project will engineer new antimicrobial nanomaterials tailored ....Nanoengineering materials to combat antimicrobial resistance. This project aims to understand how nanoengineered materials can be designed to kill bacteria and fungi without causing antimicrobial resistance. Resistance to antimicrobial drugs already leads to many thousands of deaths annually and costs society billions of dollars. Nanomaterials have unique abilities to attack microbes in multiple ways that could limit resistance. This project will engineer new antimicrobial nanomaterials tailored to selectively kill microbes with reduced likelihood of developing resistance by using synergies between inorganic nanoparticles and antimicrobial peptides. This technology could be used to prevent infections and biofilms on surfaces in a wide range of future applications, such as medical / veterinary devicesRead moreRead less
The Properties of Enteric Reflexes Recorded in Vivo. The benefit of the work will be a clear understanding of how a key body system, the digestive system is controlled. This will bring a new understanding of how intestinal function is influenced by the food that we eat and also by medicinal compounds. In the longer term, it may lead to development of dietary programs that improve digestive health and to ways to test for adverse or beneficial effects of drugs on the intestine.
Antibacterial Material Design via Mechanism-Based Mathematical Modelling. This Project aims to provide new rules for the design of novel polymer materials with antibacterial properties by employing mechanism-based mathematical modelling.
This Project expects to generate new understanding of those mechanisms which underpin the antibacterial activity of these materials, how bacteria respond to these through metabolic changes and emergence of resistance.These rules will govern material design to yi ....Antibacterial Material Design via Mechanism-Based Mathematical Modelling. This Project aims to provide new rules for the design of novel polymer materials with antibacterial properties by employing mechanism-based mathematical modelling.
This Project expects to generate new understanding of those mechanisms which underpin the antibacterial activity of these materials, how bacteria respond to these through metabolic changes and emergence of resistance.These rules will govern material design to yield new antibacterial materials with improved properties.
Expected outcomes of this project may be a novel mechanism-based mathematical model that will enable the next-generation of antibacterial materials.
This outcome will help address the increasing economic and social burden of antibiotic drug resistance in Australia.
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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
Development and Biological Chemistry of Novel Platinum Anti-Cancer Agents. "Rule-breakers", platinum anticancer complexes that do not follow the well established structure/activity relationships, have emerged as the way forward in the treatment of cancer resistant to the current generation of drugs and in reducing side effects. We have developed two new groups of "rule-breakers" and these have already demonstrated highly promising anticancer activity and novel biological behaviour. In this proje ....Development and Biological Chemistry of Novel Platinum Anti-Cancer Agents. "Rule-breakers", platinum anticancer complexes that do not follow the well established structure/activity relationships, have emerged as the way forward in the treatment of cancer resistant to the current generation of drugs and in reducing side effects. We have developed two new groups of "rule-breakers" and these have already demonstrated highly promising anticancer activity and novel biological behaviour. In this project we will (i) prepare new anticancer active platinum complexes based on these two highly promising groups of compounds and (ii) determine how these drugs work and what happens to them when in biological environments.Read moreRead less
Atomic details of antimicrobial peptides at work in live cells. This project aims to develop methods to determine the detailed structure of biologically important molecules in live cells to better understand how biomolecular structure is related to disease. The structure at the atomic level of the molecules of life is usually characterised by crystal or solution studies in model systems. However, the structure of many biologically important molecules depends on their environment. Using new instr ....Atomic details of antimicrobial peptides at work in live cells. This project aims to develop methods to determine the detailed structure of biologically important molecules in live cells to better understand how biomolecular structure is related to disease. The structure at the atomic level of the molecules of life is usually characterised by crystal or solution studies in model systems. However, the structure of many biologically important molecules depends on their environment. Using new instrumentation and labelling schemes, the project plans to use nuclear magnetic resonance methods to study antibiotics and antimicrobial peptides in live bacteria and human cells. The goal is to resolve how these molecules cross cell membranes and how biomolecular structure is related to activity, which may advance development in biotechnology and therapeutic treatments against drug-resistant infections.Read moreRead less
Advanced high resolution atomic force microscopy of biomolecules in physiological environments. The proposed research is intended to explain high resolution bioimaging problems addressed only phenomenologically before. A correct physical model would help the scientific community to optimise imaging of dynamic biological systems, extending our knowledge about the way living organisms function. With dynamic bioimaging, the mechanism of certain diseases such as Alzheimer's - where biomolecule fiber ....Advanced high resolution atomic force microscopy of biomolecules in physiological environments. The proposed research is intended to explain high resolution bioimaging problems addressed only phenomenologically before. A correct physical model would help the scientific community to optimise imaging of dynamic biological systems, extending our knowledge about the way living organisms function. With dynamic bioimaging, the mechanism of certain diseases such as Alzheimer's - where biomolecule fiber formation plays a key role - can also be addressed, thus the project has even therapeutical relevance. Furthermore, adequate description of liquid phase imaging can help engineers in the design of better hardware and software solutions, for the benefit of the bio-nanotechnological industry.Read moreRead less
Allosteric Enhancers: Leads for the Therapy of Cardiovascular Disease. Cardiovascular disease (CVD - heart, stroke and blood vessel disease) kills more people each year than cancer, AIDS and traffic accidents combined. Coronary heart disease (CHD), followed by stroke, is the largest single cause of death in Australia. Allosteric enhancers are particularly attractive drug targets for the prevention of CVD due to their ability to limit injury associated with ischaemic tissue trauma selectively ....Allosteric Enhancers: Leads for the Therapy of Cardiovascular Disease. Cardiovascular disease (CVD - heart, stroke and blood vessel disease) kills more people each year than cancer, AIDS and traffic accidents combined. Coronary heart disease (CHD), followed by stroke, is the largest single cause of death in Australia. Allosteric enhancers are particularly attractive drug targets for the prevention of CVD due to their ability to limit injury associated with ischaemic tissue trauma selectively in tissues where adenosine is elevated. Whilst the development of drugs that protect against heart attack and stroke is a difficult and long term objective, any advances toward this goal would clearly be of great benefit to the community.Read moreRead less
To gain insight into the molecular mechanisms involved in antibiotic resistance shown by Gram-negative bacteria. Bacterial infections can strike anyone and usually the body's immune system, which is designed to fight infection, defeats the invading bacteria. Sometimes however, the burden of infection proves too great, so these infections can prove fatal. For 50 years, we have relied on antibiotics to successfully treat the majority of common bacterial infections. As a result, emphasis must be pl ....To gain insight into the molecular mechanisms involved in antibiotic resistance shown by Gram-negative bacteria. Bacterial infections can strike anyone and usually the body's immune system, which is designed to fight infection, defeats the invading bacteria. Sometimes however, the burden of infection proves too great, so these infections can prove fatal. For 50 years, we have relied on antibiotics to successfully treat the majority of common bacterial infections. As a result, emphasis must be placed on the disquieting reality whilst enjoy the use of antibiotics, an inescapable cost is the development of bacterial resistance. The increasing prevalence of bacterial tolerance against beta-lactams is a problem and as a result is a most pressing health issue. Read moreRead less
Transcriptional control of antigenic variation in the malaria parasite Plasmodium falciparum. Malaria is a major health concern for the Australian Defence Personnel recently deployed in East Timor, Afghanistan and the Solomon Islands and is endemic in our immediate neighbours Indonesia and Papua New Guinea. Australia is susceptible to malaria and climate change could extend the mosquitos range to large population centres of Northern Australia causing malaria in Australia. This study would clarif ....Transcriptional control of antigenic variation in the malaria parasite Plasmodium falciparum. Malaria is a major health concern for the Australian Defence Personnel recently deployed in East Timor, Afghanistan and the Solomon Islands and is endemic in our immediate neighbours Indonesia and Papua New Guinea. Australia is susceptible to malaria and climate change could extend the mosquitos range to large population centres of Northern Australia causing malaria in Australia. This study would clarify how malaria parasites evade the host's immune response and help to protect Australia by providing drug targets for the control of this invasive disease.Read moreRead less