The Chemistry and Biochemistry of Chromium: Cancer and Nutrition. Of all of the human carcinogens, chromium(VI) has the highest level of occupational exposure, and is of increasing concern as an environmental carcinogen, as highlighted by the film Erin Brockovitch. Similarly, chromium(III) nutritional supplement consumption by humans and animals is rising rapidly, despite mounting concerns about their cancer risks. However, the complexity of Cr biochemistry is such that it is still poorly unde ....The Chemistry and Biochemistry of Chromium: Cancer and Nutrition. Of all of the human carcinogens, chromium(VI) has the highest level of occupational exposure, and is of increasing concern as an environmental carcinogen, as highlighted by the film Erin Brockovitch. Similarly, chromium(III) nutritional supplement consumption by humans and animals is rising rapidly, despite mounting concerns about their cancer risks. However, the complexity of Cr biochemistry is such that it is still poorly understood. This project aims at providing new insights into Cr biochemistry that are of relevance in evaluating risk factors for occupational and environmental exposure and for producing safer Cr dietary supplements.Read moreRead less
Peptide-based Star Polymers for Improved Biointeraction and Targeted Anticancer Therapies. The aim of this project is to develop peptide-based star polymer nanocarriers for targeted drug delivery to cancer stem cells which integrate aptamer targeting technology and biointeraction studies with blood plasma fluid. The significance of this research is it pioneers the development of a drug delivery system that minimises plasma opsonization through understanding polymer-plasma interactions, which in ....Peptide-based Star Polymers for Improved Biointeraction and Targeted Anticancer Therapies. The aim of this project is to develop peptide-based star polymer nanocarriers for targeted drug delivery to cancer stem cells which integrate aptamer targeting technology and biointeraction studies with blood plasma fluid. The significance of this research is it pioneers the development of a drug delivery system that minimises plasma opsonization through understanding polymer-plasma interactions, which in turn increases tumour specificity and cell internalisation through incorporation of targeting aptamers and triggered drug release. This project will use rational design, advanced macromolecular engineering and an interdisciplinary collaboration to generate next-generation polymer therapeutics for drug delivery.Read moreRead less
Harnessing the potential of metals in biocatalysis. The project aims to use an integrated, multi-disciplinary approach to study the properties of a group of related but functionally diverse enzymes; binuclear metallohydrolases (BMHs). These enzymes are of great relevance to protein engineers aiming to produce potent agents for bioremediation and pharmacologists interested in developing drugs. Elucidating and modulating the mode of action of BMHs is thus our main objective and should provide esse ....Harnessing the potential of metals in biocatalysis. The project aims to use an integrated, multi-disciplinary approach to study the properties of a group of related but functionally diverse enzymes; binuclear metallohydrolases (BMHs). These enzymes are of great relevance to protein engineers aiming to produce potent agents for bioremediation and pharmacologists interested in developing drugs. Elucidating and modulating the mode of action of BMHs is thus our main objective and should provide essential information to fully exploit the potential of these enzymes for practical applications. In particular, understanding how metal ions interact with BMHs and how this contributes to their reactivity is crucial to optimally understand their biotechnological potential.Read moreRead less
Single-session Introduction of Mutations in Parallel Lines (SIMPL). This project aims to develop a novel method for markedly accelerating production of genetically modified mice, which are a key 'tool' for studying biological processes and diseases. The work plans to take CRISPR, the latest gene-editing technique, to the next level by developing a novel CRISPR-based method to generate different mouse strains with distinct variations of the same gene sequences, at a fraction of the present cost a ....Single-session Introduction of Mutations in Parallel Lines (SIMPL). This project aims to develop a novel method for markedly accelerating production of genetically modified mice, which are a key 'tool' for studying biological processes and diseases. The work plans to take CRISPR, the latest gene-editing technique, to the next level by developing a novel CRISPR-based method to generate different mouse strains with distinct variations of the same gene sequences, at a fraction of the present cost and time. This project should overcome a major barrier to studying gene function with unprecedented detail, thereby opening new avenues for future research into biological processes. Thus, the outcomes from this project should impact on the entire field of biomedical research, and advance Australia's biotech industry.Read moreRead less
Tumour localisation and enhancement of anthracycline anticancer activity. The anthracyclines are one of the most widely used anticancer agents today. If the cytotoxicity of these agents can be localised to tumour cells, or their activity improved, then this will result in improved response rates, less side-effects and an improved quality of life for many patients for whom anthracycline treatment is an important part of their therapy. This will result in enormous national/community benefit to an ....Tumour localisation and enhancement of anthracycline anticancer activity. The anthracyclines are one of the most widely used anticancer agents today. If the cytotoxicity of these agents can be localised to tumour cells, or their activity improved, then this will result in improved response rates, less side-effects and an improved quality of life for many patients for whom anthracycline treatment is an important part of their therapy. This will result in enormous national/community benefit to an aging Australian population that is becoming increasingly more prone to cancer. Read moreRead less
Anticancer drug development: Enhancing the anticancer activity of mitoxantrone. Many cancer sufferers may benefit from this work if we are able to develop more active derivatives of mitoxantrone, or develop procedures to inhibit the repair of DNA lesions induced by mitoxantrone. This may result in therapies with improved response, reduced drug dosage and/or reduced side-effects. Because this work may result in one or more patents, and possibly commercialisation with Australian (and overseas) pha ....Anticancer drug development: Enhancing the anticancer activity of mitoxantrone. Many cancer sufferers may benefit from this work if we are able to develop more active derivatives of mitoxantrone, or develop procedures to inhibit the repair of DNA lesions induced by mitoxantrone. This may result in therapies with improved response, reduced drug dosage and/or reduced side-effects. Because this work may result in one or more patents, and possibly commercialisation with Australian (and overseas) pharmaceutical companies, there are potential commercial benefits to Australia. The "discovery" aspect of this work may also identify other cellular responses to mitoxantrone (ie specific genes which are re-expressed) and this may also reveal new targets to further enhance the activity of this drug.Read moreRead less
Molecular basis for the synergistic potentiation of anthracycline anticancer agents by formaldehyde-releasing prodrugs. AIMS: The overall aim is to develop a full understanding of the molecular basis for the synergistic activation of Adriamycin (and other anthracycline anticancer agents) by formaldehyde-releasing prodrugs such as AN-9.
SIGNIFICANCE: Because Adriamycin is currently one of the most widely used anticancer agents, and this activity has the potential to be dramatically enhanced by t ....Molecular basis for the synergistic potentiation of anthracycline anticancer agents by formaldehyde-releasing prodrugs. AIMS: The overall aim is to develop a full understanding of the molecular basis for the synergistic activation of Adriamycin (and other anthracycline anticancer agents) by formaldehyde-releasing prodrugs such as AN-9.
SIGNIFICANCE: Because Adriamycin is currently one of the most widely used anticancer agents, and this activity has the potential to be dramatically enhanced by the concurrent use of formaldehyde-releasing prodrugs, a biochemical understanding of these processes will provide the basis to exploit this synergy to provide improved treatment outcomes (eg, lower drug doses,reduced side-effects, improved activity against drug-resistanct tumours etc).
EXPECTED OUTCOMES: The long-term outcome of this project is commercialisation to develop products for clinical use based on this synergy (eg, drug/prodrug combinations) and ultimately the development of tumour-directed therapy to yield a tumour-localised anticancer response.Read moreRead less
The design of targetable epigenetic modifiers. The project aims to engineer enzymes as valuable tools for understanding gene expression mechanisms and potentially a technology for altering gene expression in plants, animals or humans in a targetable manner. The genetic information encoded in the DNA of all complex organisms has been shown to be augmented by decorations on both DNA and the histone proteins that package DNA. This so-called epigenetic information is important but not well understoo ....The design of targetable epigenetic modifiers. The project aims to engineer enzymes as valuable tools for understanding gene expression mechanisms and potentially a technology for altering gene expression in plants, animals or humans in a targetable manner. The genetic information encoded in the DNA of all complex organisms has been shown to be augmented by decorations on both DNA and the histone proteins that package DNA. This so-called epigenetic information is important but not well understood. The project plans to design highly specific and targetable enzymes that can interrogate and manipulate epigenetic information in living cells. Understanding the regulation of gene expression and controlling the expression of chosen genes may form a foundation for applications in agriculture, biology and medicine.Read moreRead less
Evolved enzymes and biomimetics for organophosphate degradation. Organophosphate (OP) pesticides are an indispensable part of modern agriculture - their use results in dramatically increased crop yields. However, they are toxic and can damage the environment and cause significant health problems. This project intends to evolve enzymes capable of dealing with problems caused by OPs.
Exploring the catalytic role of the Rubisco small subunit: a new target for improving carbon dioxide-fixation in plants. This project uses new biotechnological tools to improve the performance of the photosynthetic protein Rubisco, the primary carbon dioxide-fixing enzyme in plants. By supercharging photosynthesis, this research will help to boost yield and reduce water and nitrogen use in crops.