Uncovering vertebrate lifespan biodiversity with whole genome sequencing. This project aims to integrate existing data on the genetic mechanisms of lifespan evolution in model systems with a novel combination of whole genome sequencing and comparative phylogenomics to reveal the common genomic signatures of lifespan evolution in vertebrates. Expected outcomes include a perspective on the evolution of lifespan, a topic of major health interest for Australia and the rest of the developed world. Th ....Uncovering vertebrate lifespan biodiversity with whole genome sequencing. This project aims to integrate existing data on the genetic mechanisms of lifespan evolution in model systems with a novel combination of whole genome sequencing and comparative phylogenomics to reveal the common genomic signatures of lifespan evolution in vertebrates. Expected outcomes include a perspective on the evolution of lifespan, a topic of major health interest for Australia and the rest of the developed world. This will provide significant benefits, such as long-term implications for aging research, with possible business applications. It will also increase Australia’s visibility and competitiveness in the developing field of bioinformatics.Read moreRead less
Bipolar affective disorder (BP), or manic-depressive illness, is a major cause of disability and mortality worldwide. It has a lifetime prevalence of about 1% and suicide risk of about 20%. The disorder is characterised by episodes of mania or hypomania and depression, appearing in varying succession, with or without intermission. Twin, family, and adoptive studies point to a strong genetic component leading to the development of bipolar disorder, with a heritability of the order of 80%. Yet the ....Bipolar affective disorder (BP), or manic-depressive illness, is a major cause of disability and mortality worldwide. It has a lifetime prevalence of about 1% and suicide risk of about 20%. The disorder is characterised by episodes of mania or hypomania and depression, appearing in varying succession, with or without intermission. Twin, family, and adoptive studies point to a strong genetic component leading to the development of bipolar disorder, with a heritability of the order of 80%. Yet the identification of the genetic basis of the disease has proved exceedingly difficult, with numerous studies producing no definitive data. The lack of convincing results has been interpreted as an indication of complex genetic mechanisms and underlying differences between affected families and ethnic groups. Genetically isolated populations, where most individuals descend from a small number of founders, are believed to hold great potential for understanding the genetic basis of complex diseases, such as bipolar disorder. Affected subjects in such populations are likely to share the same predisposing genes, making these genes easier to identify. During the last 10 years, we have been involved in the study of bipolar disorder in one such population, with very promising results. In this project, we propose to take the research further by collecting more affected families, confirming the current positive findings and narrowing down the search to a small region, possibly a single gene. If successful, the study will be a major breakthrough which, by identifying a molecular pathway and disease mechanism, will contribute valuable and generally valid information on the biological basis of mood disorders.Read moreRead less
Genomic and molecular characterisation of a novel Australian leishmania pathogen. Leishmaniasis is the second most serious protozoal disease after malaria. This project will help characterise the first Leishmania species identified in Australia providing molecular tools to monitor the pathogen and a detailed assessment of any potential risk to human health. Comparative analysis with more pathogenic species will help identify genes and mechanisms that determine the progression of human disease le ....Genomic and molecular characterisation of a novel Australian leishmania pathogen. Leishmaniasis is the second most serious protozoal disease after malaria. This project will help characterise the first Leishmania species identified in Australia providing molecular tools to monitor the pathogen and a detailed assessment of any potential risk to human health. Comparative analysis with more pathogenic species will help identify genes and mechanisms that determine the progression of human disease leading to the potential identification of new drug and vaccine targets. The methodologies and expertise developed will be used will be available to other research groups working on infectious diseases.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160100755
Funder
Australian Research Council
Funding Amount
$371,000.00
Summary
Evolution of genome architecture. The project aims to understand how changes to genome architecture over evolutionary time are linked to the diversity of animal morphology. Our genome sequence is arranged into higher order structures that enable coordinated gene expression. The appropriate expression of genes in time and space is necessary to produce the multitude of cell types that make up a multicellular organism. Yet, to date, genome topology is poorly explored, especially between species. Th ....Evolution of genome architecture. The project aims to understand how changes to genome architecture over evolutionary time are linked to the diversity of animal morphology. Our genome sequence is arranged into higher order structures that enable coordinated gene expression. The appropriate expression of genes in time and space is necessary to produce the multitude of cell types that make up a multicellular organism. Yet, to date, genome topology is poorly explored, especially between species. The project involves comparisons of the 3D structure of genomes in divergent species. These findings are expected to inform the underlying principles of gene regulation in animals and species evolution.Read moreRead less
Insect age: an ecological genomics approach to understanding host-parasite interactions. The importance of insect age (or the age structure of a population of insects) in understanding relationships between insects and their abiotic and biotic environment has been stressed in many theoretical studies but seldom directly tested. This is because few tools exist that can accurately measure the age of a wild-caught insect with any accuracy. In this proposal we plan to use a genomics approach to deve ....Insect age: an ecological genomics approach to understanding host-parasite interactions. The importance of insect age (or the age structure of a population of insects) in understanding relationships between insects and their abiotic and biotic environment has been stressed in many theoretical studies but seldom directly tested. This is because few tools exist that can accurately measure the age of a wild-caught insect with any accuracy. In this proposal we plan to use a genomics approach to develop tools that can be used to efficiently determine the age of an insect and then apply these tools to better understand the relationship between insect age and the ability of an insect to transmit pathogens to humans, livestock or plants. These tools will also have future applicability in developing new approaches to control insect transmitted disease as well as provide methodology to determine the effectiveness of current control programs that seek to kill pest insect populations of agricultural or public health significance.Read moreRead less
Drugging the undruggable: Development of novel technologies to selectively regulate the expression of targets driving cancer and other diseases. Transcription factors are “undruggable” targets playing a principal role driving cancer. This project will create novel therapeutic strategies to inhibit transcription factors and other elusive targets differentially expressed in diseased cells, without affecting normal tissue. It proposes to construct engineered proteins able to bind and modify specifi ....Drugging the undruggable: Development of novel technologies to selectively regulate the expression of targets driving cancer and other diseases. Transcription factors are “undruggable” targets playing a principal role driving cancer. This project will create novel therapeutic strategies to inhibit transcription factors and other elusive targets differentially expressed in diseased cells, without affecting normal tissue. It proposes to construct engineered proteins able to bind and modify specific key genes deregulated in cancer, to correct their expression and stably reprogram the phenotype of the tumour cell in a normal-like state. It outlines the engineering of novel synthetic agents to block specific protein-protein interactions in cancer cells and to induce potent tumour cell death. This work will generate novel and selective therapeutics to treat un-curable forms of tumours.Read moreRead less
Chromatin barriers in Plasmodium falciparum gene regulation. Malaria is a major world disease that kills around 2 million people annually. The genome of the causative agent has now been completely sequenced, but we still know very little of how and why some genes are activated while their neighbours are turned off. I will study the DNA barriers that separate such genes, and the proteins that interact with these regions to better understand how genetic regulation functions in these parasites. A b ....Chromatin barriers in Plasmodium falciparum gene regulation. Malaria is a major world disease that kills around 2 million people annually. The genome of the causative agent has now been completely sequenced, but we still know very little of how and why some genes are activated while their neighbours are turned off. I will study the DNA barriers that separate such genes, and the proteins that interact with these regions to better understand how genetic regulation functions in these parasites. A better understanding of gene regulation in malaria parasites will help us to better combat the tricks utilised by this and other organisms to elude our immune systems.Read moreRead less
Real-time phylogenetics for food-borne outbreak surveillance. The project aims to introduce, for the first time, real-time evolutionary analysis of agricultural pathogens so that outbreaks affecting crops and the food supply can be managed precisely and rapidly. An expert team will implement a large-scale data analytics framework in user-friendly software that integrates Australian infectious disease genomics data with global data. Underpinning this work are new theory and algorithms that apply ....Real-time phylogenetics for food-borne outbreak surveillance. The project aims to introduce, for the first time, real-time evolutionary analysis of agricultural pathogens so that outbreaks affecting crops and the food supply can be managed precisely and rapidly. An expert team will implement a large-scale data analytics framework in user-friendly software that integrates Australian infectious disease genomics data with global data. Underpinning this work are new theory and algorithms that apply Sequential Monte Carlo to update phylogenetic analyses continuously as new data arrives. Expected outcomes include new knowledge of statistical algorithms for evolutionary analysis, relevant to biological disciplines beyond infectious disease; and enhanced capacity for infectious disease analysis. Read moreRead less