Plasmid maintenance and interactions with the host cell and its genome. Plasmids are extrachromosomal genetic elements that play a central role in the evolution of bacteria. They are the most dynamic component of the bacterial genome, augmenting the host chromosome by conferring a range of significant phenotypes that facilitate environmental adaptation. This project aims to elucidate fundamental aspects of the relationship between plasmids and their bacterial hosts. Significant outcomes include ....Plasmid maintenance and interactions with the host cell and its genome. Plasmids are extrachromosomal genetic elements that play a central role in the evolution of bacteria. They are the most dynamic component of the bacterial genome, augmenting the host chromosome by conferring a range of significant phenotypes that facilitate environmental adaptation. This project aims to elucidate fundamental aspects of the relationship between plasmids and their bacterial hosts. Significant outcomes include understanding the molecular basis of efficient plasmid inheritance in bacterial populations, and exploration of the innovative hypothesis that plasmids modulate expression of the host chromosome, a possibility that would profoundly alter our view of how plasmids influence host phenotype.Read moreRead less
The role of mechanosensitive (MS) ion channels in magnetoreception. The magnetic field of the Earth has for long been known to influence the behaviour and orientation of a variety of organisms. Experimental study of the magnetic sense has however, been impaired by the lack of a plausible cellular and/or molecular mechanism providing meaningful explanation for detection of magnetic fields by living organisms. Recently, mechanosensitive (MS) ion channels have been implied to play a role in magneto ....The role of mechanosensitive (MS) ion channels in magnetoreception. The magnetic field of the Earth has for long been known to influence the behaviour and orientation of a variety of organisms. Experimental study of the magnetic sense has however, been impaired by the lack of a plausible cellular and/or molecular mechanism providing meaningful explanation for detection of magnetic fields by living organisms. Recently, mechanosensitive (MS) ion channels have been implied to play a role in magnetoreception. Based on our preliminary investigations, which suggest that the activity of bacterial MS channels may be affected by magnetic fields, we propose to study effects of magnetic fields on MS ion channels in Gram-negative bacteria Escherichia coli and Magnetospirillum magnetotacticum. The project promises also to contribute towards better understanding of adverse effects of electromagnetic radiation on human health and towards understanding the mechanisms behind remote magnetic-nanoparticle mediated activation of MS ion channels.Read moreRead less
The Fine Tuned Physiology of Microaerophilic Gastric Spirilla. The aim of the project is to understand the molecular basis of fundamental properties of the physiology of enterogastric spiral bacteria of the genera Campylobacter and Helicobacter. The characteristics of these obligate microaerophiles which will be investigated are their aerobic respiratory chains, the special metabolites and enzymes involved in thiol-disulphide redox balance, and their essential requirement for carbon dioxide. Mic ....The Fine Tuned Physiology of Microaerophilic Gastric Spirilla. The aim of the project is to understand the molecular basis of fundamental properties of the physiology of enterogastric spiral bacteria of the genera Campylobacter and Helicobacter. The characteristics of these obligate microaerophiles which will be investigated are their aerobic respiratory chains, the special metabolites and enzymes involved in thiol-disulphide redox balance, and their essential requirement for carbon dioxide. Microaerobes include some bacteria, archea and protozoa. Realisation of the widespread habitats and importance of microaerophiles, has led recently to a vigorous interest in understanding their physiology. Knowledge of the basic properties of microaerophily has potential applications to Environmental Microbiology, Agriculture, Industrial Microbiology, Veterinary Science and Medicine.Read moreRead less
Structural analysis and functional inactivation of bacterial transcription complexes. RNA polymerase is an essential enzyme in all living cells. Its role is to convert the genetic information stored in genes into a message that can be converted into protein. As such, the bacterial RNA polymerase represents an ideal target for the development of new antibiotics which will be important in maintaining the health of the Australian community and also in protecting the community from the very real thr ....Structural analysis and functional inactivation of bacterial transcription complexes. RNA polymerase is an essential enzyme in all living cells. Its role is to convert the genetic information stored in genes into a message that can be converted into protein. As such, the bacterial RNA polymerase represents an ideal target for the development of new antibiotics which will be important in maintaining the health of the Australian community and also in protecting the community from the very real threat of bioterrorism organisms such as anthrax. This project is designed to identify molecules for development as new antibiotics that are effective against RNA polymerase.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
Targeted analysis of the arbuscular mycorrhizal symbiosis phenome in a model host, tomato. We will capitalise on our previous discovery of novel phenotypic variation in arbuscular mycorrhizas in mutant and wild-type tomato, to explore development and function of the symbiosis at the molecular-genetic level. We will clone and sequence the gene responsible for mycorrhiza-defective phenotypes to provide inferences on function and relations with other genes. We will determine if plant defence blocks ....Targeted analysis of the arbuscular mycorrhizal symbiosis phenome in a model host, tomato. We will capitalise on our previous discovery of novel phenotypic variation in arbuscular mycorrhizas in mutant and wild-type tomato, to explore development and function of the symbiosis at the molecular-genetic level. We will clone and sequence the gene responsible for mycorrhiza-defective phenotypes to provide inferences on function and relations with other genes. We will determine if plant defence blocks fungal colonisation in the mutant and/or varies with different wild-type phenotypes and explore molecular mechanisms of nutrient transfer from fungus to plant in relation to phenotypic diversity. The project will provide new insights into genome/phenome interactions controlling this widespread beneficial symbiosis.Read moreRead less
Molecular genetic analyses of trinucleotide repeat expansions. Several neuronal diseases like Huntington's disease, Frederick's ataxia and fragile X syndrome are caused by expansion of trinucleotide repeat sequences in the deoxyribonucleic acid (DNA). These diseases show progressive severity in subsequent generations. Here we use a simple plant model with a very similar DNA mutation to study the genetic basis of repeat expansions over several generations across populations. This proposal will im ....Molecular genetic analyses of trinucleotide repeat expansions. Several neuronal diseases like Huntington's disease, Frederick's ataxia and fragile X syndrome are caused by expansion of trinucleotide repeat sequences in the deoxyribonucleic acid (DNA). These diseases show progressive severity in subsequent generations. Here we use a simple plant model with a very similar DNA mutation to study the genetic basis of repeat expansions over several generations across populations. This proposal will improve our mechanistic understanding of genetic diseases in populations. In addition, this proposal is expected to lead to identification of potential targets and technologies that would be of interest to Australian industry.Read moreRead less
Arabidopsis DNA binding proteins that control transcription of its mitochondrial genome. The increases in crop output and quality needed to drive the agricultural sector of Australia's future economy will arise from knowledge gained by combining traditional methods and the type of cutting-edge research that identifies plant mitochondrial DNA-binding proteins and their sites of action. Mitochondria are fundamental to many agronomically important traits, including plant growth, fruit ripening and ....Arabidopsis DNA binding proteins that control transcription of its mitochondrial genome. The increases in crop output and quality needed to drive the agricultural sector of Australia's future economy will arise from knowledge gained by combining traditional methods and the type of cutting-edge research that identifies plant mitochondrial DNA-binding proteins and their sites of action. Mitochondria are fundamental to many agronomically important traits, including plant growth, fruit ripening and plant stress and disease defence. Opportunities for the rational manipulation of these and hitherto undiscovered traits will come from new knowledge generated by this project, which will develop and use frontier technologies that will keep Australia at the forefront of international research into mitochondrial structure and function.Read moreRead less
Genetic analysis of cohesin function and regulation in Drosophila. In yeast, a multiprotein complex, called cohesin, holds newly replicated chromatids together until the cell is ready to partition each chromatid into its daughter cells. We and others have shown that cohesins are regulated differently in animal cells. We propose to combine classical genetic analyses with two new and innovative techniques, time-lapse confocal microscopy of fluorescent proteins in living cells and gene-specific kno ....Genetic analysis of cohesin function and regulation in Drosophila. In yeast, a multiprotein complex, called cohesin, holds newly replicated chromatids together until the cell is ready to partition each chromatid into its daughter cells. We and others have shown that cohesins are regulated differently in animal cells. We propose to combine classical genetic analyses with two new and innovative techniques, time-lapse confocal microscopy of fluorescent proteins in living cells and gene-specific knockout techniques to study key cohesin regulators in Drosophila. These studies will provide us with novel insights into how multicellular organisms regulate the structure and stability of their chromosomes.Read moreRead less