Genetics and evolution of Shigella O antigens. We use genome scale sequencing techniques to sequence 26 O-antigen gene clusters from Shigella. With the seven already known, this will give sequences for every O-antigen of Shigella. This will be the first time that such set is fully sequenced. Shigella are human specific pathogens, have emerged with the evolution of humans. O-antigens are important for their life and pathogenicity. This project will greatly extend our knowledge of the genetic basi ....Genetics and evolution of Shigella O antigens. We use genome scale sequencing techniques to sequence 26 O-antigen gene clusters from Shigella. With the seven already known, this will give sequences for every O-antigen of Shigella. This will be the first time that such set is fully sequenced. Shigella are human specific pathogens, have emerged with the evolution of humans. O-antigens are important for their life and pathogenicity. This project will greatly extend our knowledge of the genetic basis and evolution of this important polymorphism. O-antigens are used for typing Shigella and also elicit strong immunity. The molecular data will help establish DNA based typing and vaccine development.Read moreRead less
Understanding mechanistic and systemic regulation of protein prenyltransferases. The proposed research will expand our understanding of lipid-conjugating enzymes that are critical for a multitude of normal cellular functions. We seek to reveal the basic workings of cells and help to explain the development and complexity of signalling networks in eukaryotic evolution. The findings will enable us to explore and exploit the catalytic properties of these lipid-related enzymes for applications in bi ....Understanding mechanistic and systemic regulation of protein prenyltransferases. The proposed research will expand our understanding of lipid-conjugating enzymes that are critical for a multitude of normal cellular functions. We seek to reveal the basic workings of cells and help to explain the development and complexity of signalling networks in eukaryotic evolution. The findings will enable us to explore and exploit the catalytic properties of these lipid-related enzymes for applications in biotechnology. The ultimate aim is to create novel technologies for protein production, modification and analysis that will accelerate the pace of discovery in protein research, basic cell and organism biology, diagnostics, biotechnology and drug discovery. Read moreRead less
Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastro ....Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastroenteritis. Recent statistics show that over 5 million Australians suffer from gastroenteritis each year and hospitalisation for this infection is nearly seven times higher for indigenous than non-indigenous children. Accordingly, this research has the potential to assure a healthier future for millions of Australians.Read moreRead less
Design of Polymeric Devices for Biotechnological Applications. The research project focuses on the development of functional polymer particles for diagnostic applications. Advanced polymer chemistry will be used to synthesize devices for reliable and fast diagnostic systems. The outcome of this work will help promoting and maintaining good health in Australia by developing novel technologies and advanced materials based on polymer science.
LIPID AND LIPOPROTEIN ADSORPTION AT BIOMATERIALS AND BIO-DIAGNOSTICS INTERFACES. This project aims to investigate molecular mechanisms involved in the formation of undesired biological deposits on synthetic materials and thereby help establish the scientific basis for the rational design of materials with improved compatibility with biological fluids and the engineering of a new generation of biomedical implant devices and bio-diagnostic devices. It is well known that proteins accumulate on synt ....LIPID AND LIPOPROTEIN ADSORPTION AT BIOMATERIALS AND BIO-DIAGNOSTICS INTERFACES. This project aims to investigate molecular mechanisms involved in the formation of undesired biological deposits on synthetic materials and thereby help establish the scientific basis for the rational design of materials with improved compatibility with biological fluids and the engineering of a new generation of biomedical implant devices and bio-diagnostic devices. It is well known that proteins accumulate on synthetic solid surfaces. This project proposes to investigate whether lipids and lipoproteins also play key roles in the initiation of biological adsorption processes. Combined with the study of the interfacial forces responsible, this information will guide the design of preventative strategies.Read moreRead less
Biomolecular activity modulated by interaction with nanostructures. Nanotechnological methods are able to reliably fabricate artificial nanostructures with dimensions similar to those of large biomolecules (a few to tens of nanometers). This study focuses on the interaction of artificial nanostructures with biomolecules such as proteins and DNA, and will enable scientists to better understand biomolecular recognition and binding events, which are central to all biological processes. The underst ....Biomolecular activity modulated by interaction with nanostructures. Nanotechnological methods are able to reliably fabricate artificial nanostructures with dimensions similar to those of large biomolecules (a few to tens of nanometers). This study focuses on the interaction of artificial nanostructures with biomolecules such as proteins and DNA, and will enable scientists to better understand biomolecular recognition and binding events, which are central to all biological processes. The understanding gained can then be used to design biomimetic surfaces for use in health monitoring and medical diagnostic devices with improved sensitivity, robustness and portability, thereby providing significant benefits to the health sector.Read moreRead less
Molecular Interactions in the Eubacterial Replisome: A Paradigm for Study of Dynamic Macromolecular Machines. Many pathogenic bacteria have developed resistance to antibiotics in common use, and new drugs are urgently required to kill them. Copying of their chromosomes before they divide into two new cells is essential for bacteria to live, so DNA synthesis is a good process to target for development of new antibiotics. This project will use state-of-the-art equipment available in several labora ....Molecular Interactions in the Eubacterial Replisome: A Paradigm for Study of Dynamic Macromolecular Machines. Many pathogenic bacteria have developed resistance to antibiotics in common use, and new drugs are urgently required to kill them. Copying of their chromosomes before they divide into two new cells is essential for bacteria to live, so DNA synthesis is a good process to target for development of new antibiotics. This project will use state-of-the-art equipment available in several laboratories in Australia and overseas to develop new understanding of how the molecular machine that copies DNA works. This k nowledge could lead to new drugs, and will give us new information about how cellular machines function.Read moreRead less
Proteomics of the Influenza Virus for In-field Surveillance. The influenza virus continues to pose a serious health risk to Australians and remains a leading cause of death. The molecular characterisation of emerging strains of the virus lies at the heart of current surveillance procedures vital to vaccine preparation and the development of new anti-viral drugs. This research will advance a world-first proteomics surveillance of the virus developed in this laboratory that will enable it to be ch ....Proteomics of the Influenza Virus for In-field Surveillance. The influenza virus continues to pose a serious health risk to Australians and remains a leading cause of death. The molecular characterisation of emerging strains of the virus lies at the heart of current surveillance procedures vital to vaccine preparation and the development of new anti-viral drugs. This research will advance a world-first proteomics surveillance of the virus developed in this laboratory that will enable it to be characterised in-field at the site(s) of infection outbreaks. This rapid response is vital, particularly in the event of a pandemic or a deliberate release of the virus in a bioterrorist attack.Read moreRead less
Synthesis and Characterisation of Encoded Hybrid Polymer/Gold Nanoparticles for Application in Bioassays. Bioassays are the cornerstone of in vitro diagnostic and biomedical research. This proposal will significantly contribute to these areas, by targeting an emerging technology that is crucial for their future development. The hybrid nanoparticles described in this project have the potential to replace conventional detection strategies that are currently used for bioassays. In doing so, they sh ....Synthesis and Characterisation of Encoded Hybrid Polymer/Gold Nanoparticles for Application in Bioassays. Bioassays are the cornerstone of in vitro diagnostic and biomedical research. This proposal will significantly contribute to these areas, by targeting an emerging technology that is crucial for their future development. The hybrid nanoparticles described in this project have the potential to replace conventional detection strategies that are currently used for bioassays. In doing so, they should provide significant advantages over conventional detection strategies. These advantages include increased sample throughput and conservation of biological samples, which makes possible the acceleration of patient diagnosis and drug discovery. Read moreRead less
Plasmon nanobiosensor for whole blood analysis. The new method will be able to detect specific disease markers or to identify subtle differences in protein content in complex dense analytes such as blood and other body fluids, of practical utility in diagnostic and clinical situations. It will also be relevant in other areas such as medical diagnostics of viral diseases, and for unsolved environmental monitoring problems such as the presence of specific microorganisms in industrial waste. Owing ....Plasmon nanobiosensor for whole blood analysis. The new method will be able to detect specific disease markers or to identify subtle differences in protein content in complex dense analytes such as blood and other body fluids, of practical utility in diagnostic and clinical situations. It will also be relevant in other areas such as medical diagnostics of viral diseases, and for unsolved environmental monitoring problems such as the presence of specific microorganisms in industrial waste. Owing to their design simplicity and low cost of components, the devices developed in this program will lend themselves well to the development of new commercial technologies for Australia.Read moreRead less