Extracting energy from air: mechanism of a bacterial hydrogenase. The atmosphere has recently been shown to be a key source of energy for diverse soil bacteria. Bacteria use complex enzymes, namely Huc-type hydrogenases, to harvest atmospheric hydrogen directly from air to support growth and survival. However, little is known about how Huc functions within and outside cells. By synergising expertise in microbiology, biochemistry, and chemistry, we will resolve the mechanism, assembly, and integr ....Extracting energy from air: mechanism of a bacterial hydrogenase. The atmosphere has recently been shown to be a key source of energy for diverse soil bacteria. Bacteria use complex enzymes, namely Huc-type hydrogenases, to harvest atmospheric hydrogen directly from air to support growth and survival. However, little is known about how Huc functions within and outside cells. By synergising expertise in microbiology, biochemistry, and chemistry, we will resolve the mechanism, assembly, and integration of Huc, including the basis of its remarkably high affinity and oxygen insensitivity compared to previously studied hydrogenases. This project will enable biotechnological applications, as the first study of an enzyme that extracts energy from air, and has broad ecological and biogeochemical implications.Read moreRead less
Living on air: how do bacteria scavenge atmospheric trace gases? This project aims to determine the molecular and cellular basis of atmospheric trace gas oxidation by bacteria. Bacteria have a remarkable ability to adapt to resource limitation and environmental change by entering dormant states. Our research has shown they survive in this state by using atmospheric hydrogen and carbon monoxide as energy sources. This interdisciplinary project will determine how bacteria achieve this by elucidati ....Living on air: how do bacteria scavenge atmospheric trace gases? This project aims to determine the molecular and cellular basis of atmospheric trace gas oxidation by bacteria. Bacteria have a remarkable ability to adapt to resource limitation and environmental change by entering dormant states. Our research has shown they survive in this state by using atmospheric hydrogen and carbon monoxide as energy sources. This interdisciplinary project will determine how bacteria achieve this by elucidating the regulation, mechanism, and integration of the three uncharacterised enzymes that mediate this process. Outcomes and benefits include understanding of the processes that facilitate bacterial persistence, regulate atmospheric composition, and in turn support resilience of natural ecosystems.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
The LINK to Regulating Lysine Levels in Wheat. This project aims to characterise a recently discovered allosteric mechanism called 'Ligand-Induced association by Lysine (K)' (LINK) model. LINK model regulates the function of a key biosynthetic enzyme in bacteria and plants, including agriculturally-important species such as wheat. Also, it represents a highly significant discovery to the field of biochemistry. The expected outcomes of this project include an in-depth understanding of the molecul ....The LINK to Regulating Lysine Levels in Wheat. This project aims to characterise a recently discovered allosteric mechanism called 'Ligand-Induced association by Lysine (K)' (LINK) model. LINK model regulates the function of a key biosynthetic enzyme in bacteria and plants, including agriculturally-important species such as wheat. Also, it represents a highly significant discovery to the field of biochemistry. The expected outcomes of this project include an in-depth understanding of the molecular basis of a new allosteric mechanism for regulating intracellular lysine levels, which in the longer term offers excellent potential to be manipulated for agricultural benefits.Read moreRead less
Biosynthesis of nonribosomal peptide toxins in cyanobacteria: A functional characterisation of microcystin synthetase. Microcystins are potent toxins and tumour promoters produced by cyanobacteria associated with blue-green algal blooms. This non-ribosomal peptide is produced by microcystin synthetase, a unique enzyme complex comprised of peptide synthetases, polyketide synthases, and integrated accessory enzymes. We have identified and characterised the extensive gene cluster encoding this enzy ....Biosynthesis of nonribosomal peptide toxins in cyanobacteria: A functional characterisation of microcystin synthetase. Microcystins are potent toxins and tumour promoters produced by cyanobacteria associated with blue-green algal blooms. This non-ribosomal peptide is produced by microcystin synthetase, a unique enzyme complex comprised of peptide synthetases, polyketide synthases, and integrated accessory enzymes. We have identified and characterised the extensive gene cluster encoding this enzyme. This project describes the biochemical characterisation of specific enzyme activities within microcystin synthetase and how they determine the final structure and toxicity of the many forms of microcystin. Interactions between this enzyme complex and its substrate amino acids will provide information for the genetic engineering of this and similar natural products.Read moreRead less
The regulation of signalling molecules in Saccharomyces Cerevisiae by inositol polyphosphate 5-phosphatases. Phosphoinositide signalling molecules regulate the actin cytoskeleton, secretion, vesicular trafficking and cell growth and death. We have identified, cloned and characterised a family of signal terminating enzymes called inositol polyphosphate 5-phosphatases (5-phosphatases) that regulate phosphoinositide signalling molecules. We have cloned and characterised four distinct 5-phosphatases ....The regulation of signalling molecules in Saccharomyces Cerevisiae by inositol polyphosphate 5-phosphatases. Phosphoinositide signalling molecules regulate the actin cytoskeleton, secretion, vesicular trafficking and cell growth and death. We have identified, cloned and characterised a family of signal terminating enzymes called inositol polyphosphate 5-phosphatases (5-phosphatases) that regulate phosphoinositide signalling molecules. We have cloned and characterised four distinct 5-phosphatases in the yeast Saccharomyces Cerevisiae and demonstrated by both deletion and overexpression studies that these enzymes regulate the actin cytoskeleton, endocytosis and secretion. This research proposal aims to investigate the signalling complexes the 5-phosphatases form with specific actin binding and or regulatory proteins, investigate the complex interactions of phosphoinositide lipid phosphatases and the roles they play in regulating secretion from the endoplasmic reticulum and finally characterize a novel 5-phosphatase that we have recently identified. Collectively the outcome of these studies will provide novel information about the functionallly significant signalling pathways regulated by this important enzyme family.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
Molecular mechanisms of novel bacterial copper defense proteins. This project aims to reveal molecular and cellular mechanisms used by bacteria to neutralise the destructive effects of copper. Copper is an essential trace element in living systems. It is toxic to bacteria and so plays a vital role in nutritional immunity. To counteract copper toxicity, bacteria have evolved defense mechanisms. The project will investigate a novel but poorly understood class of bacterial proteins, the suppressor ....Molecular mechanisms of novel bacterial copper defense proteins. This project aims to reveal molecular and cellular mechanisms used by bacteria to neutralise the destructive effects of copper. Copper is an essential trace element in living systems. It is toxic to bacteria and so plays a vital role in nutritional immunity. To counteract copper toxicity, bacteria have evolved defense mechanisms. The project will investigate a novel but poorly understood class of bacterial proteins, the suppressor of copper sensitivity proteins, that contribute to this key virulence trait. The expected outcomes will be fundamental new knowledge of metallo-protein diversity, bacterial virulence mechanisms, and membrane protein function with potential impact on health, environment, and biotechnology.Read moreRead less
From Chemical Architecture to Protein Surfaces. Creation of small stable molecules that reproduce key functions of important protein surfaces, would be a significant technology breakthrough with many important potential applications in science, medicine & industry. As new scientific tools they could be used to interrogate biological systems & implicate specific protein surfaces in biological/disease mechanisms. As leads to new medicines (pharmaceuticals, vaccines, diagnostics), they could offer ....From Chemical Architecture to Protein Surfaces. Creation of small stable molecules that reproduce key functions of important protein surfaces, would be a significant technology breakthrough with many important potential applications in science, medicine & industry. As new scientific tools they could be used to interrogate biological systems & implicate specific protein surfaces in biological/disease mechanisms. As leads to new medicines (pharmaceuticals, vaccines, diagnostics), they could offer new ways of impacting on infection, diseases of the aged, & preventative medicine (National Research Priorities). As new intellectual property, the technology has the potential to advance basic science at the chemistry-biology interface while providing new economic opportunities for Australia.Read moreRead less
Arsenite oxidation by a novel bacterium that is a candidate for arsenic bioremediation. The arsenic munching microbe NT-26 could help in the fight to clean up arsenic-contaminated mining waste and drinking water. Arsenic poses an environmental problem in countries such as Australia, USA and Canada owing primarily to mining activities. The problem in countries such as Bangladesh and West Bengal are even more serious as these people are dying of arsenic-related diseases as they rely on water conta ....Arsenite oxidation by a novel bacterium that is a candidate for arsenic bioremediation. The arsenic munching microbe NT-26 could help in the fight to clean up arsenic-contaminated mining waste and drinking water. Arsenic poses an environmental problem in countries such as Australia, USA and Canada owing primarily to mining activities. The problem in countries such as Bangladesh and West Bengal are even more serious as these people are dying of arsenic-related diseases as they rely on water containing arsenic as their primary source of drinking water. The outcomes of this research should provide the necessary information for removing arsenic from all types of waters.Read moreRead less