Structure, Formation And Evolution Of Multiple Antibiotic And Mercury Resistance Regions In Gram-negative Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$550,500.00
Summary
Antibiotic resistance and particularly resistance to several different antibiotics simultaneously is becoming alarmingly common in bacteria that cause infectious diseases in humans and animals. New antibiotics are proving slow to appear and the most obvious way to increase the effectiveness and the useful lifetime of existing antibiotics is though attempting to reduce the prevalence of resistant bacteria. This can only be done using good surveillance that allows the places where resistant bacter ....Antibiotic resistance and particularly resistance to several different antibiotics simultaneously is becoming alarmingly common in bacteria that cause infectious diseases in humans and animals. New antibiotics are proving slow to appear and the most obvious way to increase the effectiveness and the useful lifetime of existing antibiotics is though attempting to reduce the prevalence of resistant bacteria. This can only be done using good surveillance that allows the places where resistant bacteria and resistance genes are present in large numbers, e.g. in food-production animals, in hospitals, in the human gut or in the environment, to be identified. Very little data of this type is available internationally and even less for the Australian situation. Using recent knowledge of resistance genes and modern molecular techniques the work will identify which resistance genes and combinations of resistance genes confering resistance to antibbiotics used either in the clinic or administered to food-producing animals or both are found in Australian isolates. By examining multiply antibiotic resistant isolates from these two and other sources the flow of resistance genes and resistant bacteria between these two reservoirs will be tracked accurately. This will allow the sources relevant to difficult to treat or untreatable infections acquired in the hospital setting to be identified and appropriate action taken.Read moreRead less
Monotreme immune system provides insights into their evolutionary relationships. Genes of immunological importance will be cloned and characterised from the short-beaked echidna with the purpose of investigating the immune system in monotremes, gaining insights into the timing and order of evolutionary separation of the three extant mammalian groups:- the Prototherians (monotremes), the Metatherians (marsupials) and Eutherians (placentals), increasing understanding of the evolution of the verteb ....Monotreme immune system provides insights into their evolutionary relationships. Genes of immunological importance will be cloned and characterised from the short-beaked echidna with the purpose of investigating the immune system in monotremes, gaining insights into the timing and order of evolutionary separation of the three extant mammalian groups:- the Prototherians (monotremes), the Metatherians (marsupials) and Eutherians (placentals), increasing understanding of the evolution of the vertebrate immune system and providing the basis for making immunological reagents which are necessary for studying monotreme diseases (as a precautionary conservation strategy).Read moreRead less
Enhanced biocatalysis in organic solvents for pharmaceutical biotransformation. Enzymes such as hydrolases play an important role in biotechnology because of their extreme versatility with respect to substrate specificity and stereoselectivity. The use of lipases as catalysts for optical isomer-specific organic reactions is often limited by unacceptably low enantioselectivities. We will investigate recombinant enzymes cloned from thermophilic lipolytic bacteria for synthetic reactions in orga ....Enhanced biocatalysis in organic solvents for pharmaceutical biotransformation. Enzymes such as hydrolases play an important role in biotechnology because of their extreme versatility with respect to substrate specificity and stereoselectivity. The use of lipases as catalysts for optical isomer-specific organic reactions is often limited by unacceptably low enantioselectivities. We will investigate recombinant enzymes cloned from thermophilic lipolytic bacteria for synthetic reactions in organic solvents, especially chiral resolution of mixtures in the production of pharmaceutical intermediates. Genetic improvement of lipase enantiospecificity and regioselectivity will be achieved using in vitro evolution by recombination and screening. The outcome will be cost-effective production superior biocatalysts with specifically enhanced regiospecific, enantioselective and hydrolytic characteristics.
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Evolution in microsatellite DNA: testing models of mutation in an Australian marsupial. We aim to compare mutational events between microsatellite loci that vary in their exposure to recombination. We are able to do this because of a remarkable finding that Australian brushtail possums have multiple occurrences of a single microsatellite repeat element within the Y-chromosome and among autosomal loci. We will compare variation between the Y-linked and non Y-linked loci within and among individu ....Evolution in microsatellite DNA: testing models of mutation in an Australian marsupial. We aim to compare mutational events between microsatellite loci that vary in their exposure to recombination. We are able to do this because of a remarkable finding that Australian brushtail possums have multiple occurrences of a single microsatellite repeat element within the Y-chromosome and among autosomal loci. We will compare variation between the Y-linked and non Y-linked loci within and among individual possums and use those comparisons to distinguish between recombinant and non- recombinant mutational mechanisms. These data will provide new insights into the mutational mechanisms that drive variation in these most important molecular markers.Read moreRead less
Sex in Dragons: Evolution of sex determination in reptiles. Australia is a leader in sex determination research with major advances in our understanding attributable to Australian researchers and laboratories. This project will contribute to our prestige as a nation capable of contributing cutting edge research directions and stimulating ideas in human sex determination. Moreover, many reptiles have temperature-dependent sex determination, and so would appear appallingly vulnerable to climate ch ....Sex in Dragons: Evolution of sex determination in reptiles. Australia is a leader in sex determination research with major advances in our understanding attributable to Australian researchers and laboratories. This project will contribute to our prestige as a nation capable of contributing cutting edge research directions and stimulating ideas in human sex determination. Moreover, many reptiles have temperature-dependent sex determination, and so would appear appallingly vulnerable to climate change. Our project, will bring improved understanding of sex determination in reptiles, identify evolutionary responses of reptiles to climate change, and assist by informing society on how we might manage this issue into the future conservation of these unique Australian reptiles. Read moreRead less
Sex in Dragons: The molecular basis of genetic and environmental sex determination. How animals determine sex has been debated over decades. Particularly mysterious is that sex is determined by genes in some animals, and by temperature in others. We will study closely related dragon lizards which determine sex via genes (GSD) or temperature (TSD). We will use novel genetic, molecular and cytological aproaches to discover genes and chromosomes that control sex determination in the GSD species, an ....Sex in Dragons: The molecular basis of genetic and environmental sex determination. How animals determine sex has been debated over decades. Particularly mysterious is that sex is determined by genes in some animals, and by temperature in others. We will study closely related dragon lizards which determine sex via genes (GSD) or temperature (TSD). We will use novel genetic, molecular and cytological aproaches to discover genes and chromosomes that control sex determination in the GSD species, and explore their homologues in the TSD species. We expect this study will provide new insights to mechanisms of sex determination in all vertebrates, and demonstrate how genes and the environment interact to control the process.Read moreRead less
Organization, function and evolution of marsupial Y chromosomes. The Y chromosome of humans and other mammals contains only a few genes, most specialized for male sex and reproduction. How the Y chromosome evolved to be so peculiar has been debated for 90 years. It began as an ordinary chromosome, but has degraded until there is almost nothing left, and it is likely to disappear in about 13 million years. Molecular characterization of the Y chromosomes of distantly related mammals could serve to ....Organization, function and evolution of marsupial Y chromosomes. The Y chromosome of humans and other mammals contains only a few genes, most specialized for male sex and reproduction. How the Y chromosome evolved to be so peculiar has been debated for 90 years. It began as an ordinary chromosome, but has degraded until there is almost nothing left, and it is likely to disappear in about 13 million years. Molecular characterization of the Y chromosomes of distantly related mammals could serve to 're-run the evolutionary tape', but the Y chromosome has been left out of whole genome sequencing because it is hard to do efficiently. We developed a novel technique to isolate DNA sequences and genes on the Y chromosome in three species of marsupials, which are especially valuable because they are so different from human and mouse.Read moreRead less
Sex in Dragons: Probing the genotype-phenotype interaction in sex determination. Reptiles have two modes of sex determination: genetic (GSD) and temperature dependent (TSD). We will determine if there is an underlying mechanism of sex determination common to TSD and GSD reptiles by comparing the genomes of two sister species of dragon lizard that differ in their mode of sex determination. This study will provide new insights to the mechanism of sex determination in vertebrates and will test the ....Sex in Dragons: Probing the genotype-phenotype interaction in sex determination. Reptiles have two modes of sex determination: genetic (GSD) and temperature dependent (TSD). We will determine if there is an underlying mechanism of sex determination common to TSD and GSD reptiles by comparing the genomes of two sister species of dragon lizard that differ in their mode of sex determination. This study will provide new insights to the mechanism of sex determination in vertebrates and will test the proposition that sex determination results from the interaction between environmental influences and an underlying genetic component.Read moreRead less
Rnomics - The Role of Introns and Other Noncoding RNAs in the Evolution and Development of Complex Organisms. Approximately 98% of the transcriptional output of the human genome is noncoding RNA. The aims of the project are to (a) provide direct evidence that introns contain functional information and are part of an RNA-based regulatory network, (b) identify large numbers of new noncoding RNAs and substantiate the conclusion that noncoding RNAs genes are common in eukaryotic genomes, and (c) pr ....Rnomics - The Role of Introns and Other Noncoding RNAs in the Evolution and Development of Complex Organisms. Approximately 98% of the transcriptional output of the human genome is noncoding RNA. The aims of the project are to (a) provide direct evidence that introns contain functional information and are part of an RNA-based regulatory network, (b) identify large numbers of new noncoding RNAs and substantiate the conclusion that noncoding RNAs genes are common in eukaryotic genomes, and (c) provide supporting evidence that the higher eukaryotes have evolved a second tier of gene expression based on RNA. The project has the capacity to transform our understanding of genetic programming in the higher organisms, with considerable scientific and practical implications.Read moreRead less
Synthesis and assembly of bacterial repeat unit polysaccharides. Bacteria make an enormous range of surface polysaccharides. The complexity was first appreciated as antigenic diversity, but we now have hundreds of chemical structures and perhaps a hundred sequences of their gene clusters, but the number in nature must be many thousands. Our knowledge of gene function is growing but is not keeping up with the discovery of new sequences and structures. The aim is to determine structure and functio ....Synthesis and assembly of bacterial repeat unit polysaccharides. Bacteria make an enormous range of surface polysaccharides. The complexity was first appreciated as antigenic diversity, but we now have hundreds of chemical structures and perhaps a hundred sequences of their gene clusters, but the number in nature must be many thousands. Our knowledge of gene function is growing but is not keeping up with the discovery of new sequences and structures. The aim is to determine structure and function of key O antigen processing genes and the functions of a range of glycosyl transferases, and to use the information to generate novel gene clusters to synthesise novel polysaccharidesRead moreRead less