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
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
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.
Rubisco for all climates: unlocking the enzyme's structure-function relations for more efficient photosynthesis. This projects biotechnological research will identify structural features in the carbon dioxide (CO2)-capturing enzyme from plants that improve its performance, particularly at warmer temperatures. This knowledge is vital for predicting the influence of climate change on crop productivity and paving the way for supercharging photosynthesis to boost crop performance.
Understanding how RNA editing regulates RNA fate. This project aims to address how RNA editing mediated by ADAR1 alters the interactions of targeted RNA with the innate immune sensing system. ADAR1 editing converts adenosine to inosine within double stranded RNA. It is known that this is key to prevent activation of the innate immune sensor MDA5 by endogenous RNA. However, we do not understand why edited RNA is tolerated and unedited RNA is not. This project will generate new knowledge regarding ....Understanding how RNA editing regulates RNA fate. This project aims to address how RNA editing mediated by ADAR1 alters the interactions of targeted RNA with the innate immune sensing system. ADAR1 editing converts adenosine to inosine within double stranded RNA. It is known that this is key to prevent activation of the innate immune sensor MDA5 by endogenous RNA. However, we do not understand why edited RNA is tolerated and unedited RNA is not. This project will generate new knowledge regarding the effect of editing on how endogenous RNA is perceived by the innate immune system.Read moreRead less
A novel family of amino acid transporters in Apicomplexan parasites. Apicomplexan parasites are single celled organisms that are the causative agents of major diseases in livestock and humans. However, the basic biochemistry of these intracellular parasites is poorly understood, and there are limited treatments available for the diseases these parasites cause. The project hypothesis is that a novel family of proteins that are unique to apicomplexan parasites play a key role in the uptake of esse ....A novel family of amino acid transporters in Apicomplexan parasites. Apicomplexan parasites are single celled organisms that are the causative agents of major diseases in livestock and humans. However, the basic biochemistry of these intracellular parasites is poorly understood, and there are limited treatments available for the diseases these parasites cause. The project hypothesis is that a novel family of proteins that are unique to apicomplexan parasites play a key role in the uptake of essential nutrients (amino acids) into these organisms. This project aims to use a combination of genetic, biochemical and physiological methods to understand the function of these proteins, the role(s) that they play in apicomplexan biology, and their importance for parasite survival.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