Stuctural analysis of RNA polymerase elongation complexes. RNA polymerase (RNAP) 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. Many additional factors are required to ensure that this enzyme functions correctly in the cell. The aim of this project is to obtain structural information on a bacterial RNAP complexed with an essential transcription factor called NusA. Using this information ....Stuctural analysis of RNA polymerase elongation complexes. RNA polymerase (RNAP) 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. Many additional factors are required to ensure that this enzyme functions correctly in the cell. The aim of this project is to obtain structural information on a bacterial RNAP complexed with an essential transcription factor called NusA. Using this information, plus data already obtained on the structure of this enzyme complexed with another essential factor called sigma, we will design small molecules to inhibit the interaction of these essential factors with polymerase. These molecules will serve as leads for the development of new antibiotics.Read moreRead less
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
DNA Dynamics is Shear and Extensional Flows: Simulation and Single Molecule Experiments. The proposal seeks to establish a collaboration between Monash University and Stanford University in order to combine several recent experimental and theoretical advances that have been made by the individual groups in single molecule experimental techniques, extensional rheometry, and molecular rheology, to obtain new insights into the structure and dynamics of biopolymers. The central aim is to make a sign ....DNA Dynamics is Shear and Extensional Flows: Simulation and Single Molecule Experiments. The proposal seeks to establish a collaboration between Monash University and Stanford University in order to combine several recent experimental and theoretical advances that have been made by the individual groups in single molecule experimental techniques, extensional rheometry, and molecular rheology, to obtain new insights into the structure and dynamics of biopolymers. The central aim is to make a significant contribution towards bringing state-of-the-art techniques used for the characterization of polymeric systems to bear on the nature and origin of the elastic properties of biopolymers.Read moreRead less
The flow properties of proteins and other biopolymers. The living cell is an extraordinary organization with a vast variety of biomacromolecules carrying out myriads of functions with great specificity and accuracy. The key issue in cell biology is to unravel the structures of biopolymers and the deep connection that exists between structure and function. This interdisciplinary research program combines recent advances in experimental and theoretical rheology, with advances in protein science, t ....The flow properties of proteins and other biopolymers. The living cell is an extraordinary organization with a vast variety of biomacromolecules carrying out myriads of functions with great specificity and accuracy. The key issue in cell biology is to unravel the structures of biopolymers and the deep connection that exists between structure and function. This interdisciplinary research program combines recent advances in experimental and theoretical rheology, with advances in protein science, to investigate the response of biopolymers to deformation. This approach will lead to insights into the problem of protein folding, the interaction of biopolymers with surfaces, and the physical basis for the mechanical properties of biopolymers.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
New drugs for malaria that target histone deacetylases. There is no vaccine for malaria and current drugs are failing, contributing to millions of malaria-related deaths each year. The aim of this project is to develop new drugs to address this significant global health issue. This project will focus on drugs that act in novel ways to existing malaria drugs by targeting enzymes that are involved in altering gene expression in the parasite. These kinds of enzymes are recognised drug targets in ot ....New drugs for malaria that target histone deacetylases. There is no vaccine for malaria and current drugs are failing, contributing to millions of malaria-related deaths each year. The aim of this project is to develop new drugs to address this significant global health issue. This project will focus on drugs that act in novel ways to existing malaria drugs by targeting enzymes that are involved in altering gene expression in the parasite. These kinds of enzymes are recognised drug targets in other diseases such as cancer. The outcomes of this project will include advances in malaria drug development that build on Australian drug discovery efforts, seeding further funding opportunities from industry and other sources and contributing research training and capacity building in Australia.Read moreRead less
Does testosterone produce duds or studs? A performance-based examination of the Immunocompetence Handicap Hypothesis. The evolutionary persistence of testosterone (T) as a vertebrate reproductive hormone is viewed as a double-edged sword. On the one hand T secretion is required for development and expression of appropriate reproductive functions. On the other hand T is known to suppress immune functions and is thus considered a liability to male health. We are examining an alternate hypothesis: ....Does testosterone produce duds or studs? A performance-based examination of the Immunocompetence Handicap Hypothesis. The evolutionary persistence of testosterone (T) as a vertebrate reproductive hormone is viewed as a double-edged sword. On the one hand T secretion is required for development and expression of appropriate reproductive functions. On the other hand T is known to suppress immune functions and is thus considered a liability to male health. We are examining an alternate hypothesis: that T-induced immunosuppression benefits breeding males by protecting their physical performance levels during immune challenge. We will examine this hypothesis by quantifying the interactive effects of T and immune challenge on the aerobic capacity of male birds.Read moreRead less
FERTILIZATION IN VIVO AND IN VITRO IN AUSTRALIAN MARSUPIALS. Using reproductive technology previously undeveloped in Australian marsupials this study addresses the most significant question still unresolved in marsupial reproductive biology - 'How does fertilization occur?' We propose to investigate the morphological and functional characteristics of fertilisation and its roles in early development in marsupials, the uniqueness of these events and their evolutionary significance. These findings ....FERTILIZATION IN VIVO AND IN VITRO IN AUSTRALIAN MARSUPIALS. Using reproductive technology previously undeveloped in Australian marsupials this study addresses the most significant question still unresolved in marsupial reproductive biology - 'How does fertilization occur?' We propose to investigate the morphological and functional characteristics of fertilisation and its roles in early development in marsupials, the uniqueness of these events and their evolutionary significance. These findings will not only further our knowledge of reproduction in marsupials and shed light on the evolutionary factors underlying sperm and egg design but will provide tools for assisted breeding programs for threatened wildlife and for the regulation of over abundant species.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
Sex in the city: social harmony and conflict resolution in insect societies. Explaining the organization of cooperative societies is a significant challenge to the field of evolutionary biology. Insect societies play a pivotal role in achieving this aim, as colonies of many species persist with apparent harmony despite the presence of numerous queens competing for reproductive dominance. This study evaluates alternative hypotheses for the resolution of reproductive conflict and the maintenance a ....Sex in the city: social harmony and conflict resolution in insect societies. Explaining the organization of cooperative societies is a significant challenge to the field of evolutionary biology. Insect societies play a pivotal role in achieving this aim, as colonies of many species persist with apparent harmony despite the presence of numerous queens competing for reproductive dominance. This study evaluates alternative hypotheses for the resolution of reproductive conflict and the maintenance and evolution of cooperative societies, by examining colonies of the Australian multi-queened social wasp genus Ropalidia. Outcomes include robust tests of prominent hypotheses, explanations for cooperation's diversity and persistence, and the development of powerful molecular and behavioral techniques within Australia.
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