Evolutionary venomics: Venom system diversification in the animal kingdom. This proposal represents a tremendous opportunity for biodiscovery from the Australian toxic fauna. This will be achieved through the researcher's unique approach of investigating previously unmapped venom systems for divergent, bioactive proteins. An understanding of venomous animal protein evolution has practical implications for the treatment of envenomations - an enormous problem in Australia - as well as great pot ....Evolutionary venomics: Venom system diversification in the animal kingdom. This proposal represents a tremendous opportunity for biodiscovery from the Australian toxic fauna. This will be achieved through the researcher's unique approach of investigating previously unmapped venom systems for divergent, bioactive proteins. An understanding of venomous animal protein evolution has practical implications for the treatment of envenomations - an enormous problem in Australia - as well as great potential in drug discovery and other commercial applications. This project will provide Australian graduate and post-graduate students with finely tuned skills in cutting edge methodological techniques and a fluent understanding of molecular evolution, preparing them to be internationally competitive scientists.Read moreRead less
Molecular evolution and toxinology of colubrid snake venom toxins. This project proposes to examine the origin and evolution of venom systems in advanced snakes (Caenophidia) focusing on the colubrid radiation comprising the rear-fanged species. Demonstration by us of the presence of a potent postsynaptic neurotoxin in the Durvenoy's secretions of the Asian ratsnake Elaphe radiata, an archetypal non-venomous colubrid species, forced a fundamental rethink of venom evolution. The toxin is homologo ....Molecular evolution and toxinology of colubrid snake venom toxins. This project proposes to examine the origin and evolution of venom systems in advanced snakes (Caenophidia) focusing on the colubrid radiation comprising the rear-fanged species. Demonstration by us of the presence of a potent postsynaptic neurotoxin in the Durvenoy's secretions of the Asian ratsnake Elaphe radiata, an archetypal non-venomous colubrid species, forced a fundamental rethink of venom evolution. The toxin is homologous with the three finger toxins, previously thought unique to elapids, and supports the role of venom as a key evolutionary innovation in the diversification of advanced snakes. This project extends this work to other species and toxin families.Read moreRead less
Fish venom as a model system for the molecular evolution of defensive toxins. The key aim of this study is to undertake a thorough investigation of venoms found in distinct fish lineages, including enigmatic species such as venomous and medically important species such as the stonefish. By characterising the biodiversity of toxins found in the venoms of different fish, the evolutionary history of venom in this major vertebrate lineage can be revealed. The investigations proposed here will also d ....Fish venom as a model system for the molecular evolution of defensive toxins. The key aim of this study is to undertake a thorough investigation of venoms found in distinct fish lineages, including enigmatic species such as venomous and medically important species such as the stonefish. By characterising the biodiversity of toxins found in the venoms of different fish, the evolutionary history of venom in this major vertebrate lineage can be revealed. The investigations proposed here will also determine the functional activities of different venoms and their components. This will not only help the understanding of the medical consequences of the annual thousands of fish envenomings but also explore a largely unstudied resource for the discovery of new pharmacological diagnostics and therapeutics.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160101142
Funder
Australian Research Council
Funding Amount
$360,000.00
Summary
Unravelling the structural evolution of centipede toxins. The project intends to improve understanding of venom evolution in centipedes, and uncover new families of peptides with potential application in the agrochemical and pharmaceutical sectors. Venoms have emerged as a rich source of pharmacological tools with potential for development into therapeutics and bioinsecticides. However, venoms-based discovery has been limited by the narrow taxonomical range studied, and many groups of venomous a ....Unravelling the structural evolution of centipede toxins. The project intends to improve understanding of venom evolution in centipedes, and uncover new families of peptides with potential application in the agrochemical and pharmaceutical sectors. Venoms have emerged as a rich source of pharmacological tools with potential for development into therapeutics and bioinsecticides. However, venoms-based discovery has been limited by the narrow taxonomical range studied, and many groups of venomous animals remain overlooked. One such group is centipedes, whose venoms contain diverse novel toxins. This project aims to provide an insight into centipede toxin evolution, and establish a structure-based approach to understanding their evolution and structural diversification. The outcomes may contribute to our understanding of protein evolution and support the development of new products.Read moreRead less
Genetics of Postmenopausal Bone Loss. The major consequence of bone loss in our ageing society is fracture. At 50 years for women, the lifetime risk of sustaining an osteoporotic fracture is 50%. The consequences of these fractures, which can include reduced life expectancy, prolonged medical care, and loss of independence, have a profound socioeconomic impact in an ageing population. The proposed study offers a unique opportunity to examine the contribution of genetic factors to postmenopausal ....Genetics of Postmenopausal Bone Loss. The major consequence of bone loss in our ageing society is fracture. At 50 years for women, the lifetime risk of sustaining an osteoporotic fracture is 50%. The consequences of these fractures, which can include reduced life expectancy, prolonged medical care, and loss of independence, have a profound socioeconomic impact in an ageing population. The proposed study offers a unique opportunity to examine the contribution of genetic factors to postmenopausal osteoporosis.Read moreRead less
Pre-clinical evaluation of snake venom proteins with therapeutic potential. Australia harbors some of the most toxic snakes in the world. Their venoms contain a range of substances that are designed to rapidly immobilize and kill their prey. These include agents that lead to enhanced blood clotting; excess bleeding. We have isolated and characterized a large number of the components involved over the last several years. The aim here is to carry out pre-clinical trials in animal models to test th ....Pre-clinical evaluation of snake venom proteins with therapeutic potential. Australia harbors some of the most toxic snakes in the world. Their venoms contain a range of substances that are designed to rapidly immobilize and kill their prey. These include agents that lead to enhanced blood clotting; excess bleeding. We have isolated and characterized a large number of the components involved over the last several years. The aim here is to carry out pre-clinical trials in animal models to test the efficacy of three proteins as anti-bleeding agents and investigate several other novel components. The ultimate outcome will be the development of novel drugs that will have application in the treatment of human disorders. Read moreRead less
ARC Centre in Bioinformatics. The Australian Centre for Genome-Phenome Bioinformatics will examine how the genome comes to life in the mammalian cell during differentiation and development. We will model, visualise and experimentally validate the complex cellular systems and regulatory networks that control the transformation of genomic information into biological structure and function. We will develop novel approaches and tools to improve health, optimise agricultural production and exploit ne ....ARC Centre in Bioinformatics. The Australian Centre for Genome-Phenome Bioinformatics will examine how the genome comes to life in the mammalian cell during differentiation and development. We will model, visualise and experimentally validate the complex cellular systems and regulatory networks that control the transformation of genomic information into biological structure and function. We will develop novel approaches and tools to improve health, optimise agricultural production and exploit new cell technologies. The Centre will build critical mass and national focus in bioinformatics to generate the human capital and intellectual property that Australia needs to compete in advanced bioscience and biotechnology.Read moreRead less
The major histocompatibility complex and scent-mediated mate choice in a Procellariiform, Gould's petrel. In Australia, there are 25 species of Procellariiformes listed as threatened or endangered under the Environment Protection and Biodiversity Conservation Act 1999. Formulating comprehensive conservation plans for endangered species requires a good understanding of the species' breeding biology yet virtually nothing is known about the mechanisms involved in mate choice in the procellariiforms ....The major histocompatibility complex and scent-mediated mate choice in a Procellariiform, Gould's petrel. In Australia, there are 25 species of Procellariiformes listed as threatened or endangered under the Environment Protection and Biodiversity Conservation Act 1999. Formulating comprehensive conservation plans for endangered species requires a good understanding of the species' breeding biology yet virtually nothing is known about the mechanisms involved in mate choice in the procellariiforms. A better understanding of the traits these long-lived birds use when choosing their lifelong breeding partner could greatly benefit conservation strategies designed to protect them. This could be particularly beneficial where translocation is an option because birds being translocated could be assessed for compatibility prior to translocation.Read moreRead less
Epigenetic integration of genomic and environmental information in honey bees. Environmental factors such as nutrition, drugs or childhood neglect alter gene activity without a change to the DNA code and may result in a range of conditions such as cancer, obesity and mental illness. Such epigenetic phenomena are driven by subtle and poorly understood modifications of the genome known as DNA methylation. Our aim is to study the link between DNA methylation and environmental influences. We aspire ....Epigenetic integration of genomic and environmental information in honey bees. Environmental factors such as nutrition, drugs or childhood neglect alter gene activity without a change to the DNA code and may result in a range of conditions such as cancer, obesity and mental illness. Such epigenetic phenomena are driven by subtle and poorly understood modifications of the genome known as DNA methylation. Our aim is to study the link between DNA methylation and environmental influences. We aspire to understand how environmental signals trigger the reprogramming of transcriptional control of genetic networks that lead to contrasting phenotypic and behavioural outcomes using the honey bee modelRead moreRead less
Meiotic recombination in Neurospora crassa: a model for the process in humans and other multicellular eukaryotes. Genes are shuffled by recombination during meiosis in the sexual cycle of higher organisms. This is best understood in yeast. Our findings show Neurospora recombination differs from yeast recombination. It is more tolerant of sequence mismatch, differs in the relative frequencies of gene conversion and crossing over, has frequently interrupted conversion tracts and has transacting ge ....Meiotic recombination in Neurospora crassa: a model for the process in humans and other multicellular eukaryotes. Genes are shuffled by recombination during meiosis in the sexual cycle of higher organisms. This is best understood in yeast. Our findings show Neurospora recombination differs from yeast recombination. It is more tolerant of sequence mismatch, differs in the relative frequencies of gene conversion and crossing over, has frequently interrupted conversion tracts and has transacting genes controlling recombination hotspot activity. We propose to genetically dissect Neurospora recombination which appears to be a closer model for recombination in humans and other higher eukaryotes, where understanding recombination can assist control of genetic disease, efficient breeding in agriculture and our understanding of evolution.Read moreRead less