Biochemistry of tropoelastin and elastin. Elastin is the main protein responsible for the elasticity of vertebrate tissues. The Weiss Lab makes large quantities of full-length tropoelastin, which is crosslinked to make elastin. We want to examine the biochemistry of tropoelastin, learn how its domains participate in elastin structure and assembly, and explore cellular responses to our synthetic elastin biomaterial. Remarkably little is known of this biochemistry because elastin is a highly cross ....Biochemistry of tropoelastin and elastin. Elastin is the main protein responsible for the elasticity of vertebrate tissues. The Weiss Lab makes large quantities of full-length tropoelastin, which is crosslinked to make elastin. We want to examine the biochemistry of tropoelastin, learn how its domains participate in elastin structure and assembly, and explore cellular responses to our synthetic elastin biomaterial. Remarkably little is known of this biochemistry because elastin is a highly cross-linked and substantially insoluble macroscopic network of tropoelastin multimers. Our availability of tropoelastin and synthetic elastin now makes these studies possible.Read moreRead less
Biochemistry of tropoelastin and elastin: the molecular architecture of elastic fibre assembly. Elastin destruction drives the progression of emphysema, a major component of chronic obstructive pulmonary disease which is a major cause of death. Loss of elastin leads to profound blockage of arteries. If we are to treat these problems we need to know how to make and repair elastin. This research will enable us to discover how elastin is constructed and define its interacting partners. We will lear ....Biochemistry of tropoelastin and elastin: the molecular architecture of elastic fibre assembly. Elastin destruction drives the progression of emphysema, a major component of chronic obstructive pulmonary disease which is a major cause of death. Loss of elastin leads to profound blockage of arteries. If we are to treat these problems we need to know how to make and repair elastin. This research will enable us to discover how elastin is constructed and define its interacting partners. We will learn how to make tissue components found in parts of the body that expand and contract such as the arteries, lung and skin. We will learn about the molecular mechanisms of elastin assembly and cell interactions, which gives us the core molecular toolkit to repair elastin tissue.Read moreRead less
Variation in bacterial genomic mutation rates. Our measurement of global mutation rates will contribute to an understanding of the evolutionary properties of bacteria, the most diverse and successful organisms in the biosphere. Bacterial variation and culture richness contributes not only to ecological processes but also to emerging diseases. The studies will enhance capabilities essential in interpreting the evolution of epidemics and the kinetics of bacterial sweeps in nature. Variation also p ....Variation in bacterial genomic mutation rates. Our measurement of global mutation rates will contribute to an understanding of the evolutionary properties of bacteria, the most diverse and successful organisms in the biosphere. Bacterial variation and culture richness contributes not only to ecological processes but also to emerging diseases. The studies will enhance capabilities essential in interpreting the evolution of epidemics and the kinetics of bacterial sweeps in nature. Variation also provides the source material for exploitation of bacterial products such as antibiotics. The results from understanding a complete set of mutational changes through genomic analysis will provide the most direct estimates of variation in evolving bacteria.Read moreRead less
Mathematical models and bioinformatic analyses of bacterial genome evolution. Bacteria are vital agents in earth's biosphere, breaking down and synthesising a wide variety of compounds. Some bacteria cause disease; others are exploited for a range of biotechnological applications. Bacteria have a remarkable ability to survive and thrive in changing conditions. For example, pathogenic bacteria confronted by antibiotics easily evolve resistance to them. With the reality of climate change, we expec ....Mathematical models and bioinformatic analyses of bacterial genome evolution. Bacteria are vital agents in earth's biosphere, breaking down and synthesising a wide variety of compounds. Some bacteria cause disease; others are exploited for a range of biotechnological applications. Bacteria have a remarkable ability to survive and thrive in changing conditions. For example, pathogenic bacteria confronted by antibiotics easily evolve resistance to them. With the reality of climate change, we expect more rapid shifts in the structure of bacterial communities, possibly leading to the emergence of new pathogens. The benefits of this project are to discover how the genetic structure of bacteria confer this flexibility, and to help keep Australia at the forefront of research in bioinformatics and mathematical biology.
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Biophysical characterization of protein interactions within a transcription factor network. Gene expression is regulated in part by interactions between pairs and groups of proteins known as transcription factors and co-regulators. These proteins assemble into complexes at gene promoters and enhancers and thereby control the expression of that gene. Little is known at the molecular level of how these complexes form and how different interactions cooperate or compete with each other. In this prop ....Biophysical characterization of protein interactions within a transcription factor network. Gene expression is regulated in part by interactions between pairs and groups of proteins known as transcription factors and co-regulators. These proteins assemble into complexes at gene promoters and enhancers and thereby control the expression of that gene. Little is known at the molecular level of how these complexes form and how different interactions cooperate or compete with each other. In this proposal we aim to define a complex between two transcriptional regulators (HOP and SRF) involved in cardiac development and to begin to define other interactions that make up a transcriptional network essential for development of a normal heart.Read moreRead less
A genetic analysis of the role of an atypical hexokinase in gene regulation. This project addresses a question which is relevant to all living things-how do changes in the environment of a cell bring about a change in gene expression? The aim of this project is to investigate the role of hexokinases in gene regulation by studying the Aspergillus nidulans xprF gene, which encodes an an unusual hexokinase. Hexokinases are thought to be the glucose sensors in plants, animals and fungi, and play a ....A genetic analysis of the role of an atypical hexokinase in gene regulation. This project addresses a question which is relevant to all living things-how do changes in the environment of a cell bring about a change in gene expression? The aim of this project is to investigate the role of hexokinases in gene regulation by studying the Aspergillus nidulans xprF gene, which encodes an an unusual hexokinase. Hexokinases are thought to be the glucose sensors in plants, animals and fungi, and play a role in the development of diabetes in humans. In plants, sugars affect many processes including growth, flowering, photosynthesis, nitrogen metabolism, starch synthesis, pigmentation and response to pathogens.Read moreRead less
Environmental influence on evolutionary processes in bacterial populations. Bacterial populations exhibit remarkable adaptive capabilities in many environmental and medical settings. They respond to environmental stress in terms of altered gene expression, but what are the effects on mutation rates and fitness when cells grow at suboptimal growth rates? We plan to test whether the physiological state of an ancestral population is a determinant of a population's subsequent response to selection. ....Environmental influence on evolutionary processes in bacterial populations. Bacterial populations exhibit remarkable adaptive capabilities in many environmental and medical settings. They respond to environmental stress in terms of altered gene expression, but what are the effects on mutation rates and fitness when cells grow at suboptimal growth rates? We plan to test whether the physiological state of an ancestral population is a determinant of a population's subsequent response to selection. A simple model system using controlled culture conditions will be used to investigate the linkage between environment, mutation rate and fitness under selection. Demonstration of these linkages will have significant impacts on microbiology and understanding evolution.Read moreRead less
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
Evolutionary and ecological complexity in an experimentally controlled environment. Understanding the capacity and mechanism of microbial evolution provides the framework for developing new strategies for preventing infectious disease. If we know how evolution works, it will be possible to hamper the capacity to evolve as a mechanism of preventing new diseases and controlling existing ones. This project will provide a mechanistic description of evolution in real time under controlled conditions. ....Evolutionary and ecological complexity in an experimentally controlled environment. Understanding the capacity and mechanism of microbial evolution provides the framework for developing new strategies for preventing infectious disease. If we know how evolution works, it will be possible to hamper the capacity to evolve as a mechanism of preventing new diseases and controlling existing ones. This project will provide a mechanistic description of evolution in real time under controlled conditions. This detailed information will be used in the education of the public and in debates about evolution. The project will also train at least five students in molecular and evolutionary microbiology, essential for facing future challenges.
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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