Malarial parasite surface proteins: structure and interactions of key merozoite antigens. Malaria remains one the most lethal infectious diseases in the world today, being directly responsible for around 2 million deaths annually, many in children under 5 years of age. Related parasitic diseases affect livestock in malaria-endemic regions and more broadly. There is an urgent need for an improved understanding of how these parasites invade target red blood cells. Knowing the structures of key pro ....Malarial parasite surface proteins: structure and interactions of key merozoite antigens. Malaria remains one the most lethal infectious diseases in the world today, being directly responsible for around 2 million deaths annually, many in children under 5 years of age. Related parasitic diseases affect livestock in malaria-endemic regions and more broadly. There is an urgent need for an improved understanding of how these parasites invade target red blood cells. Knowing the structures of key proteins on the parasite cell surface will provide a deeper understanding of host-parasite interactions, as well as a basis for the design of vaccines or drugs that interfere with parasite invasion of host red blood cells. Read moreRead less
Novel compounds to disrupt protein-protein interactions. Many diseases involve aberrant interactions between proteins. Strategies to inhibit such interactions have potential as tool reagents for biological research but also as new therapies. Most drugs currently used in the clinic are small organic molecules, though these typically are not effective at disrupting protein complexes, hence alternatives are required. This proposal to examine foldamers as a novel strategy for inhibiting protein: pro ....Novel compounds to disrupt protein-protein interactions. Many diseases involve aberrant interactions between proteins. Strategies to inhibit such interactions have potential as tool reagents for biological research but also as new therapies. Most drugs currently used in the clinic are small organic molecules, though these typically are not effective at disrupting protein complexes, hence alternatives are required. This proposal to examine foldamers as a novel strategy for inhibiting protein: protein interactions could lead to the development of new drugs for the treatment of diseases where the current traditional approaches have proven ineffective.Read moreRead less
The Role of Amyloid Protein Precursor in Mammalian Copper Transport. The knowledge gained from this investigation will help us to develop new medicines for the treatment of debilitating and ever more prevalent age-related neurodegenerative diseases and will help us to illuminate the role of metals in the ageing process itself. Apart from the obvious economic and social benefits in extending the productive lifetime of its citizens, the outcomes of this project have clear commercial applications. ....The Role of Amyloid Protein Precursor in Mammalian Copper Transport. The knowledge gained from this investigation will help us to develop new medicines for the treatment of debilitating and ever more prevalent age-related neurodegenerative diseases and will help us to illuminate the role of metals in the ageing process itself. Apart from the obvious economic and social benefits in extending the productive lifetime of its citizens, the outcomes of this project have clear commercial applications. We anticipate that there will be patents that will ensue from the programme, which will be licensed to Australian interests, and contribute to the national revenue in the biotechnology and pharmaceutical sector.Read moreRead less
Neural Copper Homeostasis: the role of the Alzheimer Amyloid-beta Precursor Protein. Alzheimer's disease (AD) is creating a growing burden upon Australian medical resources. Copper plays an important role in the development of AD, and drugs designed to adjust brain copper levels are being tested for AD treatment and show therapeutic benefits. This project will determine how copper is involved in AD so that more effective drugs can be developed. Focus will primarily be on copper-binding proteins ....Neural Copper Homeostasis: the role of the Alzheimer Amyloid-beta Precursor Protein. Alzheimer's disease (AD) is creating a growing burden upon Australian medical resources. Copper plays an important role in the development of AD, and drugs designed to adjust brain copper levels are being tested for AD treatment and show therapeutic benefits. This project will determine how copper is involved in AD so that more effective drugs can be developed. Focus will primarily be on copper-binding proteins central to AD, including amyloid-beta, and their role in AD development. Upon completion of this project, we expect to better understand neural copper metabolism in health and in AD pathology, with outcomes directly applicable to therapeutic AD intervention.Read moreRead less
Evolution of a protein fold from toxin to physiological regulator: an endogenous potassium channel blocker in humans. A potassium channel blocking peptide employed by sea anemones as a toxic component of their venom is also found in proteins from a number of higher organisms, including man. In most of these proteins the function of this toxin domain is unknown. This project aims to define the structure and function of this domain in a human protein, matrix metalloprotease 23, which has possible ....Evolution of a protein fold from toxin to physiological regulator: an endogenous potassium channel blocker in humans. A potassium channel blocking peptide employed by sea anemones as a toxic component of their venom is also found in proteins from a number of higher organisms, including man. In most of these proteins the function of this toxin domain is unknown. This project aims to define the structure and function of this domain in a human protein, matrix metalloprotease 23, which has possible roles in prostate and other cancers. Our results will not only be of interest in tracing the structural and functional evolution of this toxin domain but will also provide valuable clues to its role in both the normal physiological function of matrix metalloprotease 23, as well as its potential pathological role in cancer.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
Smart Nanocapsules for Efficient Cellular Delivery of Bioactive Peptide Drugs. This project will bring about practical benefits in terms of developing efficient therapeutic drug delivery systems, which has a market growth estimated to be ca. 23% p.a. in the world. The novel encapsulation technology developed in this project is not only desirable for biomolecules but also applicable for other functional materials and will find wide applications in a number of fields, such as chemical, food proces ....Smart Nanocapsules for Efficient Cellular Delivery of Bioactive Peptide Drugs. This project will bring about practical benefits in terms of developing efficient therapeutic drug delivery systems, which has a market growth estimated to be ca. 23% p.a. in the world. The novel encapsulation technology developed in this project is not only desirable for biomolecules but also applicable for other functional materials and will find wide applications in a number of fields, such as chemical, food processing and cosmetic industries. Successful completion of the project can also strengthen our capacity to participate in new areas of research and positioning Australia at the forefront of bionanotechnology.Read moreRead less
Repulsive van der Waals forces and Brownian ratchet motors: manipulating thermal and quantum Fluctuations. A fundamental problem with miniaturizing machines and mechanical devices below the micron scale is the issue of friction and lubrication. One way to completely circumvent the need for lubrication is to use a little-studied phenomenon known as 'repulsive van der Waals forces', to create materials that fundamentally repel each other in certain fluid environments. This effect is very large at ....Repulsive van der Waals forces and Brownian ratchet motors: manipulating thermal and quantum Fluctuations. A fundamental problem with miniaturizing machines and mechanical devices below the micron scale is the issue of friction and lubrication. One way to completely circumvent the need for lubrication is to use a little-studied phenomenon known as 'repulsive van der Waals forces', to create materials that fundamentally repel each other in certain fluid environments. This effect is very large at the nanoscale and this proposal examines how such forces can be used to make 'lubricant free' motors and nanomachines. This will open up the possibility of building small and portable sensors, actuators, microfluidic devices and eventually active drug delivery systems for health applications.Read moreRead less
Controlling Anisotropic Growth of Metal Oxide Crystals in Aqueous Solution by Selective Adsorption of Small Molecules. The proposed research will enhance our ability to make both light emitting diodes (LEDs) and piezoelectric actuators from ZnO. LEDs are a high efficiency light source that save energy compared to conventional illumination sources and can be fabricated in thin films. The proposal is to also bring the technology for device fabrication to Australia where it can ultimately be used ....Controlling Anisotropic Growth of Metal Oxide Crystals in Aqueous Solution by Selective Adsorption of Small Molecules. The proposed research will enhance our ability to make both light emitting diodes (LEDs) and piezoelectric actuators from ZnO. LEDs are a high efficiency light source that save energy compared to conventional illumination sources and can be fabricated in thin films. The proposal is to also bring the technology for device fabrication to Australia where it can ultimately be used to broaden the economic base of the country. The knowledge of crystal growth rate and crystal morphology control can be applied to improvements in the efficiency of alumina production which is already an important contributor to Australian exports.Read moreRead less
Intrinsically Unstructured Proteins (IUPs): NMR characterization, prediction, and application to malarial proteome. Determination of protein structures with longer DR by NMR will enrich the DR dataset and provide a deeper understanding of protein structure-function relationships and protein folding pathways. The proposal will also provide valuable information in the key applied area of target selection in structural biology. Not all current web services are freely accessible and available servi ....Intrinsically Unstructured Proteins (IUPs): NMR characterization, prediction, and application to malarial proteome. Determination of protein structures with longer DR by NMR will enrich the DR dataset and provide a deeper understanding of protein structure-function relationships and protein folding pathways. The proposal will also provide valuable information in the key applied area of target selection in structural biology. Not all current web services are freely accessible and available services can be improved further by using more reliable training dataset or more effective algorithms, development of a national DR predictor will help Australian structural biologists increase the success rate of structure determination and provide greater insight into a range of proteomes.Read moreRead less