Diseases Of Aminoacid Transport: Genetic, Molecular And Biochemical Studies
Funder
National Health and Medical Research Council
Funding Amount
$394,173.00
Summary
Aminoacids are essential building blocks of all living things. They are taken up and retained in the body by highly specific pumps on the surface of cells. By understanding the mechanisms that control aminoacids, we will not only uncover pathways common to normal biology but also shed light on mechanisms of disease in humans. Specifically, the aminoacidurias include a number of inherited diseases of aminoacid transport that result in failure of uptake and retention of particular aminoacids. Hart ....Aminoacids are essential building blocks of all living things. They are taken up and retained in the body by highly specific pumps on the surface of cells. By understanding the mechanisms that control aminoacids, we will not only uncover pathways common to normal biology but also shed light on mechanisms of disease in humans. Specifically, the aminoacidurias include a number of inherited diseases of aminoacid transport that result in failure of uptake and retention of particular aminoacids. Hartnup disease is an inherited disorder of neutral aminoacid transport that can lead to a sun-sensitive skin rash, difficulties in controlling movements and walking and other neurological symptoms including mental retardation. A major feature of Hartnup disease is its clinical variability. We have recently identified the main genetic cause for Hartnup disease, and named the gene SLC6A19. We wish to examine whether the clinical variability observed is a consequence of genetic changes and variability in SLC6A19 and other possible genes. Two other aminoacidurias to be studied are dicarboxylic aminoaciduria and iminoglycinuria; both of which are also variable in their clinical consequences ranging from normality to mental retardation. Owing to the relative rarity of these disorders, we are fortunate to have exclusive access to individuals identified by the largest neonatal screening programme for aminoacidurias in the world, based in Canada, and other clinical cohorts within Australia. We will undertake genetic testing to localise and-or confirm the gene(s) involved in these diseases for the first time anywhere and then seek to explain their clinical variability based on functional analyses. We have established a team of researchers with complementary skills from three sites comprising the Australian Aminoaciduria Consortium. Outcomes from this project should impact on the causes and possible therapies for other important medical diseases including motor neurone disease.Read moreRead less
Evolutionary history and impact of adeno-associated viruses in Australia. Recently accrued evidence identifies Australia as an ideal closed-model system in which to elucidate the evolutionary history of a group of non-pathogenic viruses, known as adeno-associated viruses (AAVs). This project aims to trace back the evolutionary history of AAVs for tens of millions of years via molecular fossil imprints left behind by ancient viral invasions of Australian marsupial genomes. Concurrently, the poten ....Evolutionary history and impact of adeno-associated viruses in Australia. Recently accrued evidence identifies Australia as an ideal closed-model system in which to elucidate the evolutionary history of a group of non-pathogenic viruses, known as adeno-associated viruses (AAVs). This project aims to trace back the evolutionary history of AAVs for tens of millions of years via molecular fossil imprints left behind by ancient viral invasions of Australian marsupial genomes. Concurrently, the potential impact that these viral invasions had on the evolutionary development of their ancestral hosts will be investigated. This could facilitate previously unattainable insights into both AAV and marsupial evolution, with broader implications relevant to the advancement of the fields of virology and mammalian evolution.Read moreRead less
New approaches for screening cereal germplasm for enhanced microbial pathogen resistance and desirable grain texture. The trait of grain hardness (texture) is of significance to the Australian infrastructure, as exports of hard wheat contribute over 5 billion dollars per year on average to the national economy and hard wheats are also important for domestic usage. The genes responsible for grain texture also impart resistance to bacterial and fungal pathogens which can cause extensive damage. ....New approaches for screening cereal germplasm for enhanced microbial pathogen resistance and desirable grain texture. The trait of grain hardness (texture) is of significance to the Australian infrastructure, as exports of hard wheat contribute over 5 billion dollars per year on average to the national economy and hard wheats are also important for domestic usage. The genes responsible for grain texture also impart resistance to bacterial and fungal pathogens which can cause extensive damage. However, the Australian gene pool has very limited genetic diversity in grain textures and thus possibly in pathogen resistance. The project will work out the science behind these two traits and identify lines with new variants of textures and pathogen resistances, thus greatly benefiting the national infrastructure and local primary industries.Read moreRead less
Can we exploit mRNA modifications to control protein expression? Genes are encoded by DNA but are transcribed into a message called RNA before they can be translated into protein. RNA can be chemically modified at a gene-specific level, and this modification has been central to the success of RNA vaccines against COVID-19. Despite the importance of these modifications in cellular life and in biotechnology, the role of the most abundant RNA modifications is unclear. This project will investigate ....Can we exploit mRNA modifications to control protein expression? Genes are encoded by DNA but are transcribed into a message called RNA before they can be translated into protein. RNA can be chemically modified at a gene-specific level, and this modification has been central to the success of RNA vaccines against COVID-19. Despite the importance of these modifications in cellular life and in biotechnology, the role of the most abundant RNA modifications is unclear. This project will investigate how we can exploit RNA modifications to modulate protein expression in a tractable single-celled organism with a small genome, Plasmodium. This information is important because understanding gene regulation is fundamental to all life, and the role of RNA modifications is emerging as integral to biotechnology.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120102954
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Identifying and understanding the genetic regulators of cardiac development. The project aims to discover new genes involved in cardiac development so we can understand how to build a heart. Armed with this information, we can devise strategies for the repair of congenital and acquired heart disease.
Genetic dissection of cardiac morphogenesis. The human heart is critical for survival and yet, despite its importance, we still lack a basic understanding of how it forms. This project aims to discover new genes involved in cardiac development so we can understand how to build a heart. Armed with this information, this research will assist in devising strategies for the repair of congenital and acquired heart disease.
Understanding how the heart becomes more efficient. The body demands that the heart function at utmost efficiency. Trabeculae – folds within the heart lumen – maximise blood flow, contribute to chamber development and form the electrical conduction network of the heart. Problems with trabeculae formation cause cardiomyopathy and arrhythmia and yet we do not understand its basic development. The project will investigate the earliest stages of when this tissue develops its identity and examine the ....Understanding how the heart becomes more efficient. The body demands that the heart function at utmost efficiency. Trabeculae – folds within the heart lumen – maximise blood flow, contribute to chamber development and form the electrical conduction network of the heart. Problems with trabeculae formation cause cardiomyopathy and arrhythmia and yet we do not understand its basic development. The project will investigate the earliest stages of when this tissue develops its identity and examine the signalling, genetic, cellular and extracellular cues required to instruct trabeculae to form in the heart. Findings from this research will revise our understanding of when and how trabeculae form and provide key information about how to grow and repair this important tissue.Read moreRead less
CD151 and functional overlap in tetraspanins. The applicants are currently world leaders in the tetraspanin field. This project will enhance existing international collaborations to maintain and increase the applicants', and hence Australia's, international standing in this field and Australia's reputation in cell and molecular biology in general.
The project will greatly increase our understanding of this important but poorly understood family of proteins. It will also provide training opport ....CD151 and functional overlap in tetraspanins. The applicants are currently world leaders in the tetraspanin field. This project will enhance existing international collaborations to maintain and increase the applicants', and hence Australia's, international standing in this field and Australia's reputation in cell and molecular biology in general.
The project will greatly increase our understanding of this important but poorly understood family of proteins. It will also provide training opportunities for postgraduate students in state-of-the-art approaches in biotechnology.Read moreRead less