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
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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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
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
Gating, specificity and regulation of the YggB channel protein from Corynebacterium glutamicum. The proposed research will greatly contribute to our understanding of the functioning of a bacterial membrane channel/transporter, which has played a significant role in biotechnology of commercially important amino acids. A direct national benefit will result from establishing collaboration with a leading German laboratory providing expertise in protein biochemistry and molecular microbiology not ava ....Gating, specificity and regulation of the YggB channel protein from Corynebacterium glutamicum. The proposed research will greatly contribute to our understanding of the functioning of a bacterial membrane channel/transporter, which has played a significant role in biotechnology of commercially important amino acids. A direct national benefit will result from establishing collaboration with a leading German laboratory providing expertise in protein biochemistry and molecular microbiology not available in Australia. The acquired knowledge will present an original contribution which will have a strong impact on a very competitive field of molecular microbiology and biotechnology.Read moreRead less
Early evolutionary origins of mechanosensory transduction: structure, function and phylogenetic studies of the family of mechanosensitive channels in cell-walled organisms. The proposed project is based on the recent progress the applicants have made by (i) identifying a novel family of mechanosensitive (MS) channels in cell-walled organisms, which include Archaea and Bacteria (prokaryotes), as well as fungi and plants (eukaryotes), and (ii) determining basic aspects of the structural dynamics ....Early evolutionary origins of mechanosensory transduction: structure, function and phylogenetic studies of the family of mechanosensitive channels in cell-walled organisms. The proposed project is based on the recent progress the applicants have made by (i) identifying a novel family of mechanosensitive (MS) channels in cell-walled organisms, which include Archaea and Bacteria (prokaryotes), as well as fungi and plants (eukaryotes), and (ii) determining basic aspects of the structural dynamics of MscL, the prototype MS channel, using electronparamagnetic resonance spectroscopy and molecular dynamics simulations in combination with the patch clamp technique. The aim of the project is to elucidate the molecular principles underlying the function of MS channels, which is of fundamental importance for understanding of the biophysics and physiology of mechanosensory transduction throughout the biological world.Read moreRead less
Thinking about the future: The nature and development of mental time travel. This project is one of the first systematic investigations into the development of the human capacity to consider future events. A variety of novel tasks will probe what children know about the future and how it relates to their ability to reason about past events. Comparisons between children and apes will further inform us about the nature of this crucial mental skill. The findings will provide valuable information fo ....Thinking about the future: The nature and development of mental time travel. This project is one of the first systematic investigations into the development of the human capacity to consider future events. A variety of novel tasks will probe what children know about the future and how it relates to their ability to reason about past events. Comparisons between children and apes will further inform us about the nature of this crucial mental skill. The findings will provide valuable information for developing appropriate educational approaches and for our understanding of abnormalities. As international leaders in this field, we are in an ideal position to conduct this research, offer unique opportunities for postgraduate training, and to continue in Australia's outstanding tradition of excellence in basic research.Read moreRead less
Force from lipids: the role of the lipid bilayer in mechanosensory transduction. The proposed research will significantly contribute to a better understanding of the wide range of physiological processes underlying mechanosensory transduction in living cells. The direct benefit for Australian science consists of: (i) strengthening international links with leading overseas laboratories, and (ii) accessing the state-of-the-art expertise not available in Australia. The acquired knowledge will aid i ....Force from lipids: the role of the lipid bilayer in mechanosensory transduction. The proposed research will significantly contribute to a better understanding of the wide range of physiological processes underlying mechanosensory transduction in living cells. The direct benefit for Australian science consists of: (i) strengthening international links with leading overseas laboratories, and (ii) accessing the state-of-the-art expertise not available in Australia. The acquired knowledge will aid in developing and designing artificial tactile sensors inspired by their biological models studied in this project. Long-term, the project is expected to make an original contribution towards developing new technologies and novel medical applications, both of which promise to be of great national benefit.Read moreRead less