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
Targeted isolation of specific marine bacterial species associated with higher organsims for the purpose of discovering new antimicrobial compounds. Specific bacterial species that are commonly found in association with marine plants and animals often produce active secondary metabolites. The aim of this project is to apply our understanding of these bacterial-host associations to the targeted isolation of novel antimicrobials from the marine environment. While these new compounds will undoubted ....Targeted isolation of specific marine bacterial species associated with higher organsims for the purpose of discovering new antimicrobial compounds. Specific bacterial species that are commonly found in association with marine plants and animals often produce active secondary metabolites. The aim of this project is to apply our understanding of these bacterial-host associations to the targeted isolation of novel antimicrobials from the marine environment. While these new compounds will undoubtedly have a number of commercial applications this project focuses on the development of products for dental hygiene in animals. Generally, the urgent need for new antimicrobial compounds to combat the growing number of microbes that are resistant to current antibiotics highlights the importance of this project.Read moreRead less
Disrupting Chemical Communication in Bacteria: A Novel and Effective Antimicrobial Strategy. Due to increased application of antibiotics for disease control, many pathogenic bacteria have developed resistance to existing antimicrobials. The infections associated with the resistant bacteria incur a high cost in terms of human health, well being and health care costs. Thus, there is a clear need to develop new antimicrobials that have a novel mechanism of action. The technology proposed here has ....Disrupting Chemical Communication in Bacteria: A Novel and Effective Antimicrobial Strategy. Due to increased application of antibiotics for disease control, many pathogenic bacteria have developed resistance to existing antimicrobials. The infections associated with the resistant bacteria incur a high cost in terms of human health, well being and health care costs. Thus, there is a clear need to develop new antimicrobials that have a novel mechanism of action. The technology proposed here has the potential to deliver enormous health and social welfare benefits to the Australian population as well as commercial benefits to Australian industry, through provision of new, locally produced technologies for the control of bacterial virulence.Read moreRead less
Recombinant probiotics for prevention of enteric infections in piglets. Shigatoxigenic and enterotoxigenic strains of Escherichia coli cause severe diarrhoeal disease and oedema disease in piglets. The resultant morbidity and mortality is a major cause of financial loss to the pig industry both in Australia and overseas. We have conceived a highly novel approach to prevention of these diseases involving molecular mimicry of host receptors for the E. coli toxins and adhesins on the surface of a ....Recombinant probiotics for prevention of enteric infections in piglets. Shigatoxigenic and enterotoxigenic strains of Escherichia coli cause severe diarrhoeal disease and oedema disease in piglets. The resultant morbidity and mortality is a major cause of financial loss to the pig industry both in Australia and overseas. We have conceived a highly novel approach to prevention of these diseases involving molecular mimicry of host receptors for the E. coli toxins and adhesins on the surface of a harmless bacterium. Oral administration of this agent to piglets has the potential to bind free toxins in the gut and prevent colonization of the intestines by the pathogens, thereby preventing disease.Read moreRead less
Generation and Exploitation of Fermentation Products in the Chemical Synthesis of Biologically Active Compounds with Therapeutic Potential. Dramatic developments in biotechnology have provided access to genetically engineered micro-organisms capable of effecting unusual transformations so as to form novel compounds of great value in chemical synthesis. This project will combine the powers of biotechnology with those of chemical synthesis to produce compounds that have therapeutic potential in th ....Generation and Exploitation of Fermentation Products in the Chemical Synthesis of Biologically Active Compounds with Therapeutic Potential. Dramatic developments in biotechnology have provided access to genetically engineered micro-organisms capable of effecting unusual transformations so as to form novel compounds of great value in chemical synthesis. This project will combine the powers of biotechnology with those of chemical synthesis to produce compounds that have therapeutic potential in the treatment of Alzheimer's disease, cancer and viral infections.Read moreRead less
Sensing atmosphere: Understanding the HNOX-protein gas-sensing capability and how it is affected by heme-oxidation. The project investigates how gas sensing heme-proteins from the novel HNOX (Heme-Nitric Oxide) family are able to discriminate between different gaseous ligands such as O2 and NO and how oxidation of the heme alters this response. The gas-sensing capability of the HNOX proteins is crucial for organisms ranging from bacteria to humans. Thus, understanding of these signalling mechani ....Sensing atmosphere: Understanding the HNOX-protein gas-sensing capability and how it is affected by heme-oxidation. The project investigates how gas sensing heme-proteins from the novel HNOX (Heme-Nitric Oxide) family are able to discriminate between different gaseous ligands such as O2 and NO and how oxidation of the heme alters this response. The gas-sensing capability of the HNOX proteins is crucial for organisms ranging from bacteria to humans. Thus, understanding of these signalling mechanisms will have a strong impact on many scientific fields from the control of pathogen growth to human blood pressure regulation. This collaboration will establish Australian scientists and as world-leading in the field of NO and redox signalling. This development will also be of substantial benefit for the training of the next generation of Australian students and scientists.Read moreRead less
Molecular evolution of a model oligomeric enzyme from bacterial extremophiles. The national benefits of this research program include insight into the sustainability of marine microorganisms that play an important role in Australia's diverse ecosystem, the development and applications of frontier technologies including high-performance computing on the world's largest supercomputer facility for life science research, and knowledge impacting on the discovery of novel antibiotics that target patho ....Molecular evolution of a model oligomeric enzyme from bacterial extremophiles. The national benefits of this research program include insight into the sustainability of marine microorganisms that play an important role in Australia's diverse ecosystem, the development and applications of frontier technologies including high-performance computing on the world's largest supercomputer facility for life science research, and knowledge impacting on the discovery of novel antibiotics that target pathogenic bacteria, like Golden Staph. This program will also train several young Australians in highly sought after skills, including bacteriology, biophysics, enzymology, molecular biology, molecular modelling, protein chemistry and structural biology. Read moreRead less
Inhibitors of meso-diaminopimelic acid (meso-DAP) and lysine biosynthesis: targeting dihydrodipicolinate synthase. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics with novel modes of action. This project aims to generate new drug candidates that target dihydrodipicolinate synthase (DHDPS) - the first enzyme in the synthesis of the bacterial cell wall - using a triple-pronged approach. This novel approach will allow for the development of new drugs to tr ....Inhibitors of meso-diaminopimelic acid (meso-DAP) and lysine biosynthesis: targeting dihydrodipicolinate synthase. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics with novel modes of action. This project aims to generate new drug candidates that target dihydrodipicolinate synthase (DHDPS) - the first enzyme in the synthesis of the bacterial cell wall - using a triple-pronged approach. This novel approach will allow for the development of new drugs to treat a range of pathogenic bacteria, including "Golden Staph".Read moreRead less
A Unique Target in the Purine Biosynthesis of the Pathogen Helicobacter pylori. The uptake systems of purine and analogues of the human pathogen Helicobacter pylori will be characterised because they can be utilised to introduce cytotoxic compounds into the cells. The first step in de novo purine biosynthesis of the bacterium is catalysed by two different enzymes, which are components of other biosynthetic pathways. These unique properties make them excellent potential therapeutic targets. Their ....A Unique Target in the Purine Biosynthesis of the Pathogen Helicobacter pylori. The uptake systems of purine and analogues of the human pathogen Helicobacter pylori will be characterised because they can be utilised to introduce cytotoxic compounds into the cells. The first step in de novo purine biosynthesis of the bacterium is catalysed by two different enzymes, which are components of other biosynthetic pathways. These unique properties make them excellent potential therapeutic targets. Their individual combined activities in purine biosynthesis will be characterised in situ and in vitro. Isogenic mutants with inactivated genes encoding for these enzymes will be constructed to investigate their role in the survival of the organism.Read moreRead less