Structure and dynamics of a multiprotein-mRNA complex involved in the regulation of gene expression. RNA/protein interactions are now recognised as a major control point in the regulation of gene-expression. Proteins such as HuR and the poly(C)-binding proteins (PCBPs) act to stabilise and transport specific messenger (m)RNAs, and thus determine their translation levels. In contrast to such an important function, very little is known about these protein/mRNA interactions at an atomic level. The ....Structure and dynamics of a multiprotein-mRNA complex involved in the regulation of gene expression. RNA/protein interactions are now recognised as a major control point in the regulation of gene-expression. Proteins such as HuR and the poly(C)-binding proteins (PCBPs) act to stabilise and transport specific messenger (m)RNAs, and thus determine their translation levels. In contrast to such an important function, very little is known about these protein/mRNA interactions at an atomic level. The current study will investigate the structural and biophysical properties of a recently discovered HuR/PCBP/mRNA complex implicated in the regulation of androgen receptor expression. This information has the potential to assist in the development of drugs to reduce AR expression in prostate cancer.Read moreRead less
Nanoparticles to combat cellular dysfunction. This project aims to design, synthesise and characterise nanoparticles that can mediate the adverse effects of reactive oxygen species. The project expects to develop nanoparticles with tailored chemical functionality to modulate the concentration of reactive oxygen species and develop a platform technology for addressing conditions where reactive species are overproduced. The project will research how nanoparticles’ physicochemical properties affect ....Nanoparticles to combat cellular dysfunction. This project aims to design, synthesise and characterise nanoparticles that can mediate the adverse effects of reactive oxygen species. The project expects to develop nanoparticles with tailored chemical functionality to modulate the concentration of reactive oxygen species and develop a platform technology for addressing conditions where reactive species are overproduced. The project will research how nanoparticles’ physicochemical properties affect their activity, and how they affect cellular function, tissue morphology and particle transport in a biological milieu. The project is expected to benefit the advanced manufacturing, veterinary and medical sectors and could lead to new chemotherapeutics.Read moreRead less
Work life after a diagnosis of breast, prostate and colorectal cancer: Major disruption or work as usual. Each year, over 40,000 working-age individuals (as well as their families and workplaces) are affected by a diagnosis of cancer. This novel and important study will, for the first time in Australia, identify the extent and effects of loss of skilled workers from the workforce because of a diagnosis of breast, prostate or colorectal cancer and will lead to the development of new interventions ....Work life after a diagnosis of breast, prostate and colorectal cancer: Major disruption or work as usual. Each year, over 40,000 working-age individuals (as well as their families and workplaces) are affected by a diagnosis of cancer. This novel and important study will, for the first time in Australia, identify the extent and effects of loss of skilled workers from the workforce because of a diagnosis of breast, prostate or colorectal cancer and will lead to the development of new interventions that help people to recover from cancer. This project is critical to help advance health and labour policies in Australia which currently faces an ageing population, global economic unrest and rising unemployment.Read moreRead less
Triggering the release of polymer bound platinum drugs. Platinum drugs are found to be highly efficient as anti-cancer drugs. Their side-effects however, limit their application. Nanoparticles are developed that bind the platinum drug tightly as long as the drug circulates in the blood stream, but releases the drug as soon as it reaches the tumour. To treat prostate cancer, the nanoparticle will be attached to a targeting moiety - a monoclonal antibody - that facilitates the effective delivery t ....Triggering the release of polymer bound platinum drugs. Platinum drugs are found to be highly efficient as anti-cancer drugs. Their side-effects however, limit their application. Nanoparticles are developed that bind the platinum drug tightly as long as the drug circulates in the blood stream, but releases the drug as soon as it reaches the tumour. To treat prostate cancer, the nanoparticle will be attached to a targeting moiety - a monoclonal antibody - that facilitates the effective delivery to the prostate cancer cells, but leaves healthy cells unaffected. This proposal aims to develop suitable synthetic pathway to enhance the treatment of cancer by using appropriate delivery vehicles. Read moreRead less
Guarding and evolving the genome: interactions between DNA-repair enzymes and damaged DNA. The application of structural biology techniques to the area of DNA repair allows us to understand the full implications linking genes and proteins to the molecular mechanisms of diseases such as cancer and hereditory conditions. Studies in this highly internationally competitive area are already established in the Bond laboratory, which has recently relocated to Australia. The use of forward-thinking stru ....Guarding and evolving the genome: interactions between DNA-repair enzymes and damaged DNA. The application of structural biology techniques to the area of DNA repair allows us to understand the full implications linking genes and proteins to the molecular mechanisms of diseases such as cancer and hereditory conditions. Studies in this highly internationally competitive area are already established in the Bond laboratory, which has recently relocated to Australia. The use of forward-thinking structural biology approaches to solve difficult technical problems will foster collaborations within Australia and with leading laboratories abroad, providing excellent up-to-date research training for students and postdoctoral researchers.
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Multivalent drug delivery carrier for the targeted delivery of platinum anticancer agents to hepatocytes. Hepatocellular carcinoma (HCC) is often treated with chemotherapy using cytotoxic drugs. This systemic treatment results in the distribution of the drug throughout the body. Employing a polymer particle as a drug carrier for these drugs ensures a temporal control of the release and therefore supply of the drug within the body. By attaching carbohydrate moieties onto the surface of the polyme ....Multivalent drug delivery carrier for the targeted delivery of platinum anticancer agents to hepatocytes. Hepatocellular carcinoma (HCC) is often treated with chemotherapy using cytotoxic drugs. This systemic treatment results in the distribution of the drug throughout the body. Employing a polymer particle as a drug carrier for these drugs ensures a temporal control of the release and therefore supply of the drug within the body. By attaching carbohydrate moieties onto the surface of the polymer particle the drug carrier can specifically be recognized by cell receptors, thus allowing a targeted delivery of the drug to the desired area in the body. A range of carbohydrate-based drug carriers will be synthesized and tested towards their interaction with hepatocytes to allow optimisation of this drug carrier system.
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Navigating tipping points in complex dynamical systems. This project aims to use applied mathematics to investigate the onset of tipping points in dynamical systems. Working with clinicians and practicing engineers, the project aims to contribute to the development of new treatment regimes for dynamical diseases and develop improved management strategies for resource focussed engineering industries. This should provide significant benefit to many areas, including the personalised treatment of di ....Navigating tipping points in complex dynamical systems. This project aims to use applied mathematics to investigate the onset of tipping points in dynamical systems. Working with clinicians and practicing engineers, the project aims to contribute to the development of new treatment regimes for dynamical diseases and develop improved management strategies for resource focussed engineering industries. This should provide significant benefit to many areas, including the personalised treatment of disease.Read moreRead less
BIOSYNTHESIS OF A FUNGAL TOXIN AND ITS ROLE IN PLANT DISEASE. This project will determine how an important class of toxic molecules, epipolythiodioxopiperazines (EPTs), are made by fungi. Knowledge of the domains and actions of these genes in the biosynthetic pathway may lead to the ability to engineer secondary metabolites with altered specificity, and drugs that alleviate symptoms of secondary fungal toxicoses associated with leukemia, organ transplants and HIV AIDS. Also this project will a ....BIOSYNTHESIS OF A FUNGAL TOXIN AND ITS ROLE IN PLANT DISEASE. This project will determine how an important class of toxic molecules, epipolythiodioxopiperazines (EPTs), are made by fungi. Knowledge of the domains and actions of these genes in the biosynthetic pathway may lead to the ability to engineer secondary metabolites with altered specificity, and drugs that alleviate symptoms of secondary fungal toxicoses associated with leukemia, organ transplants and HIV AIDS. Also this project will also elucidate the role of an EPT, sirodesmin, in blackleg of canola, a disease that costs the Australian canola industry up to $50 million in losses annually. Outcomes of this project may lead to novel blackleg disease control strategies. Read moreRead less
Mitochondrially targeted anti-cancer drugs modulate the mitochondrial genome. Successful cancer management requires novel therapeutical approaches. This project will test the effect of a new class of compounds that target mitochondria, the powerhouse of the cells, where they suppress expression of mitochondrial genes. By this mechanism, cancers that are resistant to apoptosis induction can be inhibited.
Core-shell nanoparticle from polymers with pendant cyclodextrins. A better drug delivery system will be developed for the treatment of cancer with albendazole. These nanoparticles enhance the circulation time in the body, but also facilitate the delivery of the drug to the site of the tumour, which will increase the efficacy of the treatment. The nanoparticles are obtained by processing polymers with pendant cyclodextrin groups, which are a type of complex sugars. Aim of this work is the explora ....Core-shell nanoparticle from polymers with pendant cyclodextrins. A better drug delivery system will be developed for the treatment of cancer with albendazole. These nanoparticles enhance the circulation time in the body, but also facilitate the delivery of the drug to the site of the tumour, which will increase the efficacy of the treatment. The nanoparticles are obtained by processing polymers with pendant cyclodextrin groups, which are a type of complex sugars. Aim of this work is the exploration of synthetic routes to generate nanoparticles. Tailoring the underpinning polymer structure of these nanoparticles will allow the optimisation of the release of albendazole from the drug carrier, thus improving cancer treatment.Read moreRead less