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.
Glaucoma is the second leading cause of blindness in the world affecting approximately 70 million people. Glaucoma can occur at any age but the commonest type occurs in middle to old age. The disease has a genetic basis and can be inherited. As a result we have been studying the genetics of the disease in two large families from Tasmania. We hope to identify the genes involved in disease causation using a number of genetic techniques. Once mutations in a disease gene have been identified from af ....Glaucoma is the second leading cause of blindness in the world affecting approximately 70 million people. Glaucoma can occur at any age but the commonest type occurs in middle to old age. The disease has a genetic basis and can be inherited. As a result we have been studying the genetics of the disease in two large families from Tasmania. We hope to identify the genes involved in disease causation using a number of genetic techniques. Once mutations in a disease gene have been identified from affected individuals we will then be in a position to look for mutations in other family members and identify those individuals at risk of developing disease. Improvements in our understanding of how these genes are involved in disease causation will allow us to offer diagnostic testing to the wider community and develop better therapeutic interventions for treatment.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE150100083
Funder
Australian Research Council
Funding Amount
$540,000.00
Summary
A high throughput phenomics facility for pace of life traits in animals. A high throughput phenomics facility for pace of life traits in animals: This project seeks to create the first high-throughput phenomic facility for animals in Australia. The molecular revolution has brought unprecedented capacity to understand genetic variation. Genetic variation is now better understood and more easily and cheaply characterised than the physical traits that organisms exhibit. Linking phenotypic variation ....A high throughput phenomics facility for pace of life traits in animals. A high throughput phenomics facility for pace of life traits in animals: This project seeks to create the first high-throughput phenomic facility for animals in Australia. The molecular revolution has brought unprecedented capacity to understand genetic variation. Genetic variation is now better understood and more easily and cheaply characterised than the physical traits that organisms exhibit. Linking phenotypic variation to genetic variation represents the major challenge in harnessing the power of the biomolecular age. This facility will accommodate animals from marine, freshwater and terrestrial systems across a diverse array of phyla. It will allow Australian researchers to leverage advances in high throughput genomic technologies to address a major bottleneck in biology.Read moreRead less
Circulating Low -molecular Weight AGEs In The Development And Progression Of Diabetic Complications
Funder
National Health and Medical Research Council
Funding Amount
$297,523.00
Summary
High levels of sugars seen in patients with diabetes leads to damage of many organs including the heart, the eyes and the kidneys. These high sugars cause damage through a number of mechanisms, one being the formation of advanced glycation end products or AGEs, formed by the irreversible reaction between proteins and glucose. This reaction leads to a change in the shape and function of AGE-modified molecules that progressively contributes to organ damage. AGEs also bind and activate specific rec ....High levels of sugars seen in patients with diabetes leads to damage of many organs including the heart, the eyes and the kidneys. These high sugars cause damage through a number of mechanisms, one being the formation of advanced glycation end products or AGEs, formed by the irreversible reaction between proteins and glucose. This reaction leads to a change in the shape and function of AGE-modified molecules that progressively contributes to organ damage. AGEs also bind and activate specific receptors that promote the damage and scarring of tissue. Where the glucose concentration is high, AGEs accumulate much more quickly. This is one reason why patients with good sugar control do better than those who are unable to control their blood sugars. The importance of this AGE pathway is illustrated by the fact that blocking the formation of AGEs is able to prevent kidney damage in animals with diabetes. In addition, exposure to AGEs can cause diabetes-like changes in the absence of high sugars. Our laboratory is a world leader in the study of the advanced glycation and methods blocking this process. The research proposed will investigate circulating levels of AGEs in experimental animals and patients with diabetes, and correlate them with the development and progression of complications of diabetesRead moreRead less
About time; a new biology for the mineralocorticoid receptor . Temporal control of cell function aligns biological pathways with environmental cues and is critical for optimal heath in mammals. This project will shed light on how a hormone receptor, the MR, modulates time keeping of biological clock time in cells. We will bring together cutting edge genetic modals and bioinformatic approaches with a unique set of research models to define the interaction between the MR and the circadian clock a ....About time; a new biology for the mineralocorticoid receptor . Temporal control of cell function aligns biological pathways with environmental cues and is critical for optimal heath in mammals. This project will shed light on how a hormone receptor, the MR, modulates time keeping of biological clock time in cells. We will bring together cutting edge genetic modals and bioinformatic approaches with a unique set of research models to define the interaction between the MR and the circadian clock and its role in the normal biology of the heart. New data will significantly enhance our understanding of the biology of MR and cortisol for the circadian time keeping function in peripheral tissues, and gain a clearer understand how our heart cells adapt to environmental circadian disruptors such as shift work. Read moreRead less
Buffering the ecosystem impact of invasive cane toads. This project aims to address the devastating ecological problems caused by invasive species, by developing a novel approach that does not rely upon eradicating the invader through training vulnerable native predators not to eat toxic cane toads. Expected outcomes of this project include building a broad coalition of conservation-focused groups, from private land-owners and local businesses through to Indigenous groups and government and non- ....Buffering the ecosystem impact of invasive cane toads. This project aims to address the devastating ecological problems caused by invasive species, by developing a novel approach that does not rely upon eradicating the invader through training vulnerable native predators not to eat toxic cane toads. Expected outcomes of this project include building a broad coalition of conservation-focused groups, from private land-owners and local businesses through to Indigenous groups and government and non-government agencies across the entire Kimberley region. It will also result in the evaluation of methods for deployment of taste-aversion at a landscape scale. This should provide significant benefits by conserving vulnerable fauna and building a powerful network within a region of high biodiversity in tropical Australia.Read moreRead less
Protein-protein interactions in amyloid deposits. The aggregation of specific proteins to form insoluble amyloid fibrils is characteristic of several age-related diseases such as type-II diabetes, Alzheimer's disease and Parkinson's disease. In vivo amyloid deposits also contain three prominent non-fibrillar protein components, namely serum amyloid P component, apolipoprotein E and alpha1-antichymotrypsin. These non-fibrillar amyloid components bind to a wide variety of amyloid fibrils, irresp ....Protein-protein interactions in amyloid deposits. The aggregation of specific proteins to form insoluble amyloid fibrils is characteristic of several age-related diseases such as type-II diabetes, Alzheimer's disease and Parkinson's disease. In vivo amyloid deposits also contain three prominent non-fibrillar protein components, namely serum amyloid P component, apolipoprotein E and alpha1-antichymotrypsin. These non-fibrillar amyloid components bind to a wide variety of amyloid fibrils, irrespective of the nature of the protein constituent. This proposal is to identify the structural basis for this recognition process, the capacity of non-fibrillar components to cross-link amyloid fibrils to form networks and the influence of these interactions on amyloid fibril cytotoxicity.Read moreRead less
Making Green Guard® greener: enhancing the efficacy of a biopesticide. The project aims to identify naturally occurring micro-organisms to increase the effectiveness of Green Guard ®, which is a biopesticide used against the Australian plague locust. The project will use next-generation sequencing and other molecular techniques to potentially identify candidate microbes or combinations of microbes that can be added to Green Guard to enhance locust susceptibility. The project also aims to quantif ....Making Green Guard® greener: enhancing the efficacy of a biopesticide. The project aims to identify naturally occurring micro-organisms to increase the effectiveness of Green Guard ®, which is a biopesticide used against the Australian plague locust. The project will use next-generation sequencing and other molecular techniques to potentially identify candidate microbes or combinations of microbes that can be added to Green Guard to enhance locust susceptibility. The project also aims to quantify the interactive impact of temperature and nutrition on immune function, disease resistance and host-plant quality of plague locusts; and to explore the combined effects of temperature, habitat and Green Guard, in combination with candidate microbes or pathogens, on the behaviour and collective movement of locusts. It is anticipated that this will have implications for management and control strategies.Read moreRead less
Dissemination And Virulence Properties Of The She Pathogenicity Island Of Shigella Flexneri.
Funder
National Health and Medical Research Council
Funding Amount
$110,625.00
Summary
Bacterial species belonging to the genus Shigella are responsible for intestinal diseases ranging from mild diarrhoea to life threatening bacillary dysentery. Such diseases kill over a million people, mainly infants in developing countries, every year and lead to serious morbidity and mortality even in industrialised countries with well developed health care systems. In many cases the virulence of Shigella species is augmented by large fragments of DNA, called pathogenicity islands, that carry g ....Bacterial species belonging to the genus Shigella are responsible for intestinal diseases ranging from mild diarrhoea to life threatening bacillary dysentery. Such diseases kill over a million people, mainly infants in developing countries, every year and lead to serious morbidity and mortality even in industrialised countries with well developed health care systems. In many cases the virulence of Shigella species is augmented by large fragments of DNA, called pathogenicity islands, that carry genes which contribute to the development of disease (pathogenesis) in humans. Pathogenicity islands are important genetic elements which appear to spread independantly throughout bacterial populations and therefore contribute to the emergence of new virulence traits in bacteria. Recently, we identified two related pathogenicity islands carried by both Shigella flexneri and other species of the genus Shigella. The two pathogenicity islands belong to a unique class of genetic elements found in Shigella species and virulent strains of the intestinal bacterium E. coli. Our current study is aimed at (1) understanding the mechanisms by which one of these islands, the she pathogenicity island, spreads from one bacterial strain to another to introduce disease-producing or virulence genes to new bacteria and (2) to study how the sigA virulence gene, carried on the she pathogenicity island, contributes to disease development in humans. We know that sigA encodes a protein toxin which contributes to the loss of fluid from the intestines of rabbits that have been experimentally infected with Shigella flexneri. We propose to study the structure and function of the SigA protein to determine how it interacts with tissues to produce a pathological state. Such studies will enhance our understanding of the process of disease development and contribute to the investigation and assessment of new strategies for therapeutic intervention.Read moreRead less
Are alternative histones important regulators of transcription in Plasmodium falciparum? Malaria parasites depend on tightly controlled expression of their genes for maintaining infection and causing disease. The project will identify mechanisms of gene control used by parasites; these mechanisms may provide targets for malaria therapies.