Dissecting The Pseudoexfoliation Syndrome With Complementary Genetic, Proteomic And Biophysical Strategies
Funder
National Health and Medical Research Council
Funding Amount
$490,352.00
Summary
Pseudoexfoliation syndrome (PEX) is an eye condition in which flaky material deposits in the eye, greatly increasing the risk of cataract and glaucoma which can lead to blindness. PEX is also associated with heart disease, strokes and aneurysms. Cataract surgery in PEX patients has a higher rate of complications. In this project we will determine the nature of PEX material and why it forms. This knowlege will facilitate better diagnosis and treatment of PEX preventing associated blindness.
Investigating The Role Of The UPF3B Gene And Nonsense Mediated RNA Decay (NMD) Process In Mental Retardation.
Funder
National Health and Medical Research Council
Funding Amount
$572,710.00
Summary
Intellectual disability is a frequent and important medical problem. Genetic and environmental factors contribute about equally to the aetiology of intellectual disability. Estimated 1-3% of population suffer from a form of intellectual disability. Among the genetic factors contributing to intellectual disability are genes, and their mutations, on one of the human chromosomes, chromosome X. We have been studying human X-chromosome genes for many years and discovered in excess of 20 novel genes c ....Intellectual disability is a frequent and important medical problem. Genetic and environmental factors contribute about equally to the aetiology of intellectual disability. Estimated 1-3% of population suffer from a form of intellectual disability. Among the genetic factors contributing to intellectual disability are genes, and their mutations, on one of the human chromosomes, chromosome X. We have been studying human X-chromosome genes for many years and discovered in excess of 20 novel genes causing various forms of intellectual disability. Surprisingly the number of genes, in which mutations cause various forms of intellectual disability is unexpectedly high. Just on the human X-chromosome we expect in excess of 200 such genes, which is nearly 30% of the gene content of this chromosome. We propose to study a novel gene, UPF3B, we recently identified to be mutated in a form of intellectual disability. The normal function of this gene and its protein is known to a certain extent. The UPF3B protein plays a role of a guardian of other genes in human (and also other species) cells. The role of the UPF3B protein is to prevent erroneous genetic information to be used for the building of proteins with potentially toxic effects to the organism. In our patients this process clearly malfunctions as a consequence of the damaged UPF3B gene. We propose to shed some more light in to the molecular intricacies of this process with the aim to better understand the mechanics of the process. Families, which participate in our studies and have this gene involved will benefit from the availability of direct test. Multiple other families around the world are also likely to benefit, now or in the future.Read moreRead less
Refining the timescale of human evolution and dispersal using ancient DNA. Understanding the timescale of human evolution and migration is a key goal of genetic analysis. It provides the foundation for studying our evolutionary and demographic history, our relationships to other hominids and our impact on the natural world. This project aims to use ancient DNA data to improve estimates of our evolutionary timescale.
Development of efficient CRISPR gene drives in mice. This project aims to generate new tools for vertebrate pest management through development of cutting-edge gene drive technology in mice. Vertebrate pests cost Australia over $1 billion each year in agricultural losses and environmental damage and novel strategies are required to tackle this challenge. Newly developed “gene drives”, which can rapidly spread through populations, have enormous potential for the sustained management and even erad ....Development of efficient CRISPR gene drives in mice. This project aims to generate new tools for vertebrate pest management through development of cutting-edge gene drive technology in mice. Vertebrate pests cost Australia over $1 billion each year in agricultural losses and environmental damage and novel strategies are required to tackle this challenge. Newly developed “gene drives”, which can rapidly spread through populations, have enormous potential for the sustained management and even eradication of pests. This project aims to develop gene drive technology in mice as a prototypical vertebrate pest species. The project will potentially deliver valuable tools that directly impact Australia’s Science and Research Priority on Food.Read moreRead less
Small is beautiful: Did gene-rich regions of mammal chromosomes evolve from microchromosomes? Most birds and reptile genomes feature many tiny microchromosomes. These are not junk, as previously thought, but contain most of the genes. Mammals lack microchromosomes, but contain gene-rich regions with similar attributes. We suggest that microchromosomes originated by genome duplication, and evolved into the gene-rich regions of mammalian chromosomes. We will test this hypothesis by comparing seque ....Small is beautiful: Did gene-rich regions of mammal chromosomes evolve from microchromosomes? Most birds and reptile genomes feature many tiny microchromosomes. These are not junk, as previously thought, but contain most of the genes. Mammals lack microchromosomes, but contain gene-rich regions with similar attributes. We suggest that microchromosomes originated by genome duplication, and evolved into the gene-rich regions of mammalian chromosomes. We will test this hypothesis by comparing sequences and genes in microchromosomes of birds, reptiles and monotremes. This will clarify the origin and evolution of the ?microgenome?, establish its suitability as a model for vertebrate genome organisation, and demonstrate whether microchromosomes are the ancestors of the gene-rich regions of mammalian chromosomes.Read moreRead less
Developing new methods to retrieve and analyse preserved genetic information. This project will position Australia at the leading edge of research into preserved DNA, and will use innovative molecular biology approaches to develop a range of new forensic, archaeological and medical applications. It will build Australian knowledge and scientific capacity by developing core expertise and training personnel in areas important for biosecurity, customs and quarantine, forensics/counter-terrorism, and ....Developing new methods to retrieve and analyse preserved genetic information. This project will position Australia at the leading edge of research into preserved DNA, and will use innovative molecular biology approaches to develop a range of new forensic, archaeological and medical applications. It will build Australian knowledge and scientific capacity by developing core expertise and training personnel in areas important for biosecurity, customs and quarantine, forensics/counter-terrorism, and studies of climate change. It will also create and foster research innovation in molecular biology with spin-offs for evolution, archaeology, medical and conservation biology research, and will also encourage involvement with the rapidly expanding field of genomics and bioinformatics.Read moreRead less
Investigating The Antimicrobial Activity Of Zinc At The Host-pneumococcal Interface
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Streptococcus pneumoniae is a human-only bacterium that is responsible for killing more than one million people every year. This project will analyse how the human immune system fights this bacterium, and subsequently, how the bacteria manages to subvert these attacks and survive in the human host. This will provide crucial information for developing new drugs against this pathogen, in an attempt to combat the ever-increasing problem of antibiotic resistance.
Potential of gene drives to eliminate incursions of Drosophila suzukii. This project aims to test the efficacy and evolutionary stability of different types of gene drives, and model whether gene drives can be used to eliminate incursions of Drosophila suzukii into Australia. It is now possible to use genome editing technology to alter populations of organisms using ‘gene drives’. Multiple strategies have been conceived with a major distinction between those that aim to eliminate populations ver ....Potential of gene drives to eliminate incursions of Drosophila suzukii. This project aims to test the efficacy and evolutionary stability of different types of gene drives, and model whether gene drives can be used to eliminate incursions of Drosophila suzukii into Australia. It is now possible to use genome editing technology to alter populations of organisms using ‘gene drives’. Multiple strategies have been conceived with a major distinction between those that aim to eliminate populations versus those that aim to modify populations. This project will examine these strategies in two fly species, the model, Drosophila melanogaster and the devastating pest of horticulture, Drosophila suzukii. The project expects to assess a gene drive strategy to control the invasive pest that threatens the Australian soft-skinned fruit industries.Read moreRead less
Adaptation to life in the dark: genomic analyses of blind beetles. This project aims to utilise a unique Australian model system based on multiple, independently-evolved subterranean water beetles to explore the adaptive and regressive changes in the genome that occur when surface species colonise subterranean habitats. This project focuses on the evolution of Heat Shock protein (Hsp) genes that play critical roles in adaptation to environmental stress and the process of de-canalisation, the rel ....Adaptation to life in the dark: genomic analyses of blind beetles. This project aims to utilise a unique Australian model system based on multiple, independently-evolved subterranean water beetles to explore the adaptive and regressive changes in the genome that occur when surface species colonise subterranean habitats. This project focuses on the evolution of Heat Shock protein (Hsp) genes that play critical roles in adaptation to environmental stress and the process of de-canalisation, the release of cryptic genetic variation that can allow novel morphologies to evolve in new environments. The project expects to provide further understanding of how species may potentially adapt to environmental stresses in the future, including climate change.Read moreRead less
Is regressive evolution associated with loss of gene function in subterranean animals? This project aims to investigate a fundamental biological process: the evolutionary basis for how non-functional characters, such as eyes in subterranean animals, are lost. It will use a unique model system based on eyeless water beetles, and utilise novel new genomic tools to test whether loss of characters results from gene inactivation.