Smart bio-mimetic self-assembled gels for biomedical applications. Advanced materials that can be used to deliver drugs, repair scars and damaged tissue are the holy grail of regenerative medicine. Recently, a class of materials called self-assembled gels have shown enormous potential in this regard. Self-assembled gels have already demonstrated their use in drug delivery and are showing great promise in the treatment of spinal injuries. This project will create an even smarter version of these ....Smart bio-mimetic self-assembled gels for biomedical applications. Advanced materials that can be used to deliver drugs, repair scars and damaged tissue are the holy grail of regenerative medicine. Recently, a class of materials called self-assembled gels have shown enormous potential in this regard. Self-assembled gels have already demonstrated their use in drug delivery and are showing great promise in the treatment of spinal injuries. This project will create an even smarter version of these gels with biological activity, especially targeting cancer and suppressing tumour growth after surgery. Our approach will help to ensure that Australians can take a leading role in this highly exciting new area of biomedical research.Read moreRead less
Solid-phase synthesis of sulfopeptides for evaluation of chemokine-receptor recognition. This research program will develop new chemical methods for preparing biologically active molecules that contain sulphate. These molecules have important functions in controlling blood clotting, hormone activity, immune responses, and AIDS or malarial infection. The new chemical methods will be used to study the interactions of two groups of proteins that control the movement of white blood cells in inflamma ....Solid-phase synthesis of sulfopeptides for evaluation of chemokine-receptor recognition. This research program will develop new chemical methods for preparing biologically active molecules that contain sulphate. These molecules have important functions in controlling blood clotting, hormone activity, immune responses, and AIDS or malarial infection. The new chemical methods will be used to study the interactions of two groups of proteins that control the movement of white blood cells in inflammatory responses. The research will provide insights into the biochemistry of inflammation and will contribute to the development of new therapies for diseases affecting young Australians (allergy, asthma, and viral infections) as well as the elderly (atherosclerosis and arthritis).Read moreRead less
Surface Chemistry meets Cell Biology: Molecular Level Control of Surface Architecture for Cell Adhesion and Migration. Biotechnological applications such as tissue engineering, bone supports, implantable materials, cell assays and biosensors all require detailed knowledge of how cells interact with their environment. The proposed research aims to provide this knowledge by developing unique modified surfaces to investigate white blood cell migration and adhesion. Additional expected outcome will ....Surface Chemistry meets Cell Biology: Molecular Level Control of Surface Architecture for Cell Adhesion and Migration. Biotechnological applications such as tissue engineering, bone supports, implantable materials, cell assays and biosensors all require detailed knowledge of how cells interact with their environment. The proposed research aims to provide this knowledge by developing unique modified surfaces to investigate white blood cell migration and adhesion. Additional expected outcome will contribute to our understanding of the many fundamental cellular processes such as cell growth, differentiation and cell death as well as the molecular basis of diseases such as inflammation, cancer, cardiovascular diseases and wound healing. This research program will establish Australia as a leading force in this new research field.Read moreRead less
Dynamic Force Microscopy of small molecular assemblies. The possibility of manipulating a single molecule seems at first unreal, indeed 5 years ago it was pure science fiction. Through the gaining popularity of the Atomic Force Microscope (AFM) many perspectives about the molecular world are changing. Macroscopic effects such as adhesion and lubrication are now discussed in light of measurements made with this instrument. Newer work includes the observation of single protein unfolding experim ....Dynamic Force Microscopy of small molecular assemblies. The possibility of manipulating a single molecule seems at first unreal, indeed 5 years ago it was pure science fiction. Through the gaining popularity of the Atomic Force Microscope (AFM) many perspectives about the molecular world are changing. Macroscopic effects such as adhesion and lubrication are now discussed in light of measurements made with this instrument. Newer work includes the observation of single protein unfolding experiments. The biophysics oriented project detailed in this application will extend the AFM: into multi-molecular systems formed by self-assembly, such as cell membranes; into polyelectrolyte-surface interactions; and, finally into the sequencing of DNA.Read moreRead less
Metal Virulence and Therapeutic Factors in Pathogen Bioinorganic Chemistry. The aim is to gain insights into the bioinorganic chemistry that occurs when immune system cells encounter pathogens and the soles of virulence factors and immune system enhancing roles of metal ions. Pathogenic bacteria and fungi accumulate chromium (Cr) in their membranes/outer capsules, which we discovered is likely to be a previously unknown, but important, virulence factor. Hyperaccummulation of nickel (Ni) is also ....Metal Virulence and Therapeutic Factors in Pathogen Bioinorganic Chemistry. The aim is to gain insights into the bioinorganic chemistry that occurs when immune system cells encounter pathogens and the soles of virulence factors and immune system enhancing roles of metal ions. Pathogenic bacteria and fungi accumulate chromium (Cr) in their membranes/outer capsules, which we discovered is likely to be a previously unknown, but important, virulence factor. Hyperaccummulation of nickel (Ni) is also involved in virulence, whereas vanadium (V) enhances the immune system response to these pathogens. Fundamental insights into these roles of Cr, Ni and V will be investigated using advanced spectroscopic, imaging and biochemical techniques. These insights will provide new knowledge on the innate immune system.Read moreRead less
Engineered Polymer Nanoparticles: A Potent Weapon Against Cancer. Cervical cancer is the commonest cause of cancer death in women under the age of 50 worldwide, the 8th most common cancer among women in Australia, and is the leading cause of cancer death in Aboriginal women. While a vaccine is available to prevent HPV-mediated disease, it would not impact upon death rates for at least 25 years. The systemic delivery of RNAi offers to best opportunity to solve this problem. The delivery devices w ....Engineered Polymer Nanoparticles: A Potent Weapon Against Cancer. Cervical cancer is the commonest cause of cancer death in women under the age of 50 worldwide, the 8th most common cancer among women in Australia, and is the leading cause of cancer death in Aboriginal women. While a vaccine is available to prevent HPV-mediated disease, it would not impact upon death rates for at least 25 years. The systemic delivery of RNAi offers to best opportunity to solve this problem. The delivery devices will be designed with precision and function to meet the delivery needs in vivo. These polymer structures will be suitable for use in drug and gene delivery providing Australian products with advanced features and capabilities, significantly improving product performance.Read moreRead less
Cellular mechanics in unusual systems. This project aims to provide a fundamental understanding of how biomechanics influences stem cells under normal and microgravity conditions. This will be achieved by developing and validating simulated microgravity conditions on earth and establishing a valid system that mimics the extracellular matrix of living tissue in low gravity. The materials and technology generated will allow detailed insight into how force influences focal adhesion between cells an ....Cellular mechanics in unusual systems. This project aims to provide a fundamental understanding of how biomechanics influences stem cells under normal and microgravity conditions. This will be achieved by developing and validating simulated microgravity conditions on earth and establishing a valid system that mimics the extracellular matrix of living tissue in low gravity. The materials and technology generated will allow detailed insight into how force influences focal adhesion between cells and how this force is transferred from cell-to-cell in tissue. The findings from this project are expected to have significant benefit in controlling cell fate in space and on earth.Read moreRead less
Defining the biosynthesis and immunological properties of complex bacterial glycolipids. We will study how sugar-lipids are made by industrially, agriculturally and medically important bacteria, and how they interact with the immune system. This will provide new insights into cell wall biosynthesis of importance to the biotechnology industry and identify new reagents for manipulating the immune system.
Mechanisms and consequences of oxidation of glycosaminoglycans, proteins and proteoglycans by myeloperoxidase-derived oxidants. Atherosclerosis (hardening of the arteries) is responsible for the death of 40% of the population of developed, and developing, countries including Australia. Rupture of the fibrous cap of atherosclerotic lesions is responsible for most sudden deaths from heart disease and stokes, but is a poorly understood process. Evidence has been presented for a role for oxidation r ....Mechanisms and consequences of oxidation of glycosaminoglycans, proteins and proteoglycans by myeloperoxidase-derived oxidants. Atherosclerosis (hardening of the arteries) is responsible for the death of 40% of the population of developed, and developing, countries including Australia. Rupture of the fibrous cap of atherosclerotic lesions is responsible for most sudden deaths from heart disease and stokes, but is a poorly understood process. Evidence has been presented for a role for oxidation reactions in weakening the structure of lesions and making them prone to rupture. Little is known about the fundamental chemistry of such damage; this will be addressed in the proposed program. The data obtained will underpin the development of new preventative and protective strategies to minimise lesion rupture and deaths from this major disease.Read moreRead less
Mechanisms and consequences of myeloperoxidase-mediated damage to glycosaminoglycans, proteins and proteoglycans. Atherosclerosis (hardening of the arteries) is responsible for the death of 40% of the population of developed, and developing, countries including Australia. Rupture of the fibrous cap of atherosclerotic lesions is responsible for most sudden deaths from heart disease and stokes, but is a poorly understood process. Evidence has been presented for a role for oxidation reactions in we ....Mechanisms and consequences of myeloperoxidase-mediated damage to glycosaminoglycans, proteins and proteoglycans. Atherosclerosis (hardening of the arteries) is responsible for the death of 40% of the population of developed, and developing, countries including Australia. Rupture of the fibrous cap of atherosclerotic lesions is responsible for most sudden deaths from heart disease and stokes, but is a poorly understood process. Evidence has been presented for a role for oxidation reactions in weakening the structure of lesions and making them prone to rupture. Little is known about the fundamental chemistry of such damage; this will be addressed in the proposed program. The data obtained will underpin the development of new preventative and protective strategies to minimise lesion rupture and deaths from this major disease.Read moreRead less