Phasevarions of Haemophilus influenzae: mechanisms and origins of a novel epigenetic system controlling coordinated random switching in expression of multiple genes. Central to the utilisation of biological information is our ability to identify and interpret DNA sequence information from genomes. In bacteria that cause disease, these investigations can identify key aspects of the infectious process or potential components of vaccines or new targets for antibiotics. Our recent work has identifie ....Phasevarions of Haemophilus influenzae: mechanisms and origins of a novel epigenetic system controlling coordinated random switching in expression of multiple genes. Central to the utilisation of biological information is our ability to identify and interpret DNA sequence information from genomes. In bacteria that cause disease, these investigations can identify key aspects of the infectious process or potential components of vaccines or new targets for antibiotics. Our recent work has identified a new genetic system, the 'phasevarion', that mediates random expression of multiple genes. The proposed research aims to advance our understanding of gene expression at the most basic level, revealing how bacteria generate diverse populations to evade environmental and immune stresses, and facilitating improved interpretation and use of DNA sequences for researchers and industry in this field.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
Estimation of non-additive genetic variance for complex traits using genome-wide single nucleotide polymorphyisms and sequence data. Finding genes for traits of importance in agriculture, ecology and human health depends on understanding the genetic basis of these traits. This project will investigate whether variation in traits in humans, cattle and wild sheep are influenced by gene-gene interactions.
The genetic architecture and evolution of quantitative traits. Most important traits are controlled by many genes and by the environment, however there is little knowledge of how many genes are involved in these complex traits and what their effects are. This project will describe the number of genes and their effects for complex traits in humans and livestock and explain how these genes evolve.
Control of Wolbachia replication: maintaining a stable symbiosis. This project will use a comparative genomics approach to better understand how Wolbachia infections of insects are able to maintain themselves in insects without causing pathology. The results will allow us to better understand a distinguishing characteristic of an intracellular symbiont, namely replication control. The results also have the potential to lead to new approaches to insect pest control through a better understanding ....Control of Wolbachia replication: maintaining a stable symbiosis. This project will use a comparative genomics approach to better understand how Wolbachia infections of insects are able to maintain themselves in insects without causing pathology. The results will allow us to better understand a distinguishing characteristic of an intracellular symbiont, namely replication control. The results also have the potential to lead to new approaches to insect pest control through a better understanding of how Wolbachia might be used to skew insect population age structure.Read moreRead less
Mutational genetic variance and the fitness optimum. Mutation and selection are ubiquitous forces in nature, but we do not understand how genetic variation produced by mutation is maintained in the presence of selection that depletes it. The recent discovery of apparent stabilising selection on traits with high levels of genetic variation provides a new approach to understanding this paradox.
Discovery Early Career Researcher Award - Grant ID: DE200100425
Funder
Australian Research Council
Funding Amount
$409,364.00
Summary
Genetic and Molecular Consequences of Non-Random Mating in Humans. This project aims to develop and apply novel statistical methods to quantify the effects on a large number of complex traits of two forms of non-random mating in humans, that is inbreeding and assortative mating. The innovation in this proposal lies in integrating multi-level phenotypes with next-generation sequencing data collected in more than half a million study participants. Expected outcomes of this research include advance ....Genetic and Molecular Consequences of Non-Random Mating in Humans. This project aims to develop and apply novel statistical methods to quantify the effects on a large number of complex traits of two forms of non-random mating in humans, that is inbreeding and assortative mating. The innovation in this proposal lies in integrating multi-level phenotypes with next-generation sequencing data collected in more than half a million study participants. Expected outcomes of this research include advanced analytical methods to perform this integration and dissection of the biological consequences of non-random mating in humans at an unprecedented phenotypically detailed scale. The benefit of this project will be to identify new drivers of mate choice that can contribute to economic, health and social inequalities. Read moreRead less
The genomics of adaptation in Wolbachia pipientis, an emerging biocontrol agent. Australians are increasingly exposed to insect-transmitted diseases such as dengue fever. Novel biocontrol methods using the bacterium Wolbachia aim to control insect populations to reduce disease transmission. Our research will be the first to investigate genomic variation and the process of adaptation to new insect hosts in Wolbachia. The novel data and understanding of evolutionary processes we generate will be c ....The genomics of adaptation in Wolbachia pipientis, an emerging biocontrol agent. Australians are increasingly exposed to insect-transmitted diseases such as dengue fever. Novel biocontrol methods using the bacterium Wolbachia aim to control insect populations to reduce disease transmission. Our research will be the first to investigate genomic variation and the process of adaptation to new insect hosts in Wolbachia. The novel data and understanding of evolutionary processes we generate will be critical for screening bacterial biocontrol candidates and designing biocontrol release strategies. It will also strengthen the position of Australian research as a world-leader in the fusion of post-genomics and applied microbiology. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE140100958
Funder
Australian Research Council
Funding Amount
$394,112.00
Summary
Understanding how shared between-sex genetic variance constrains the evolution of sexual dimorphism. Differences between males and females in the expression of shared traits have been of lasting interest to biologists. One fundamental question, which is as yet poorly understood, regards the extent to which a common genome restricts the independent evolution of the sexes. This project proposes a novel way of examining the degree to which the shared genetic architecture restricts the evolution of ....Understanding how shared between-sex genetic variance constrains the evolution of sexual dimorphism. Differences between males and females in the expression of shared traits have been of lasting interest to biologists. One fundamental question, which is as yet poorly understood, regards the extent to which a common genome restricts the independent evolution of the sexes. This project proposes a novel way of examining the degree to which the shared genetic architecture restricts the evolution of the sexes and the costs this imposes on population fitness. The results from the proposed experiments will give a clearer picture of how current measures reflect the true genetic constraint imposed on the sexes from a shared genetic architecture.Read moreRead less
A comparative genomics approach to understanding host-endosymbiont interactions. Australia's unique ecosystems are vulnerable to invasion by exotic pests that threaten agriculture and human health. The bacterial symbiont Wolbachia is found in many major pests of agricultural and medical importance. Our results will give insights into how Wolbachia spreads into host populations and improve its use as a tool to impair insect transmission of disease, e.g. as an agent to carry genes into an insect p ....A comparative genomics approach to understanding host-endosymbiont interactions. Australia's unique ecosystems are vulnerable to invasion by exotic pests that threaten agriculture and human health. The bacterial symbiont Wolbachia is found in many major pests of agricultural and medical importance. Our results will give insights into how Wolbachia spreads into host populations and improve its use as a tool to impair insect transmission of disease, e.g. as an agent to carry genes into an insect population that limit disease transmission. Our results will also make fundamental contributions to understanding host-parasite evolution, host-parasite communication, and insect developmental processes, and will be of interest to a large international community of researchers in this field. Read moreRead less