Mapping Of Genetic Traits In Experimental Models Using Databases
Funder
National Health and Medical Research Council
Funding Amount
$237,750.00
Summary
The project aims to detect genes that influence human traits. These traits could be a disease such as diabetes or they may be much less sinister, representing hearing range as an example. Many of these traits are difficult to detect because they are governed by many genes which may also interact with the environment to influence the trait. In order to detect genes in these traits we would like to simplify the complex interactions by eliminating the environment as a potential cause or concentrati ....The project aims to detect genes that influence human traits. These traits could be a disease such as diabetes or they may be much less sinister, representing hearing range as an example. Many of these traits are difficult to detect because they are governed by many genes which may also interact with the environment to influence the trait. In order to detect genes in these traits we would like to simplify the complex interactions by eliminating the environment as a potential cause or concentrating on a particular population where the incidence appears to be much greater. In human populations we have no control over the environmental exposures and we cannot restrict their movements. For this reason many genetic studies have been conducted in mice. Many strains of mice have been generated. Their environment can be strictly controlled, enabling a much better identification of disease genes. Since mice and humans share much of their genome they also share many of their genes and are often afflicted by the same diseases. Thus if we identify genes in mice we have a very good chance of identifying the equivalent human genes. The completion of sequencing for the human genome is being closely followed by the completion of the mouse genome, precisely because mice have been used for over 100 years for genetic studies. The data generated from these sequencing efforts and prior genetic studies is now accumulating in vast databases. These databases of DNA information can be used to map genes for traits. The idea is to determine the trait measurement for many mice in different strains and compare these trait levels to the DNA state (genotype) of markers in the genome of the strains. If these are associated it indicates that the marker is situated close to a gene influencing the trait. This narrows the search considerably. Without this strategy we would have the daunting task of identifiying trait genes from many thousands of potential candidates.Read moreRead less
Statistical Methods for Next Generation Genome-Wide Association Studies. This project aims to develop cutting-edge statistical methods to analyse large genomic datasets and identify genetic variants associated with inter-individual differences in various human traits. Knowledge of trait-associated DNA variants is instrumental in understanding how natural selection has shaped human traits. By integrating genomic data from diverse and underrepresented populations, this project further expects to c ....Statistical Methods for Next Generation Genome-Wide Association Studies. This project aims to develop cutting-edge statistical methods to analyse large genomic datasets and identify genetic variants associated with inter-individual differences in various human traits. Knowledge of trait-associated DNA variants is instrumental in understanding how natural selection has shaped human traits. By integrating genomic data from diverse and underrepresented populations, this project further expects to contribute to the equitable use of genomic technologies in humans, regardless of geographical origins. Expected outcomes of this research include novel analysis methods and software tools, which should broadly and significantly benefit gene discovery in other species, including those of agricultural relevance.Read moreRead less
Development Of A Generic Strategy For The Stabilisation Of Peptide-based Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$443,196.00
Summary
There is huge interest in the development of bioactive peptides and proteins for the treatment of a wide range of diseases. However, there are still a number of hurdles that need to be overcome before this source of promising pharmaceuticals can fulfil their vast potential. One of the biggest challenges in the development of peptides and proteins as drugs is overcoming their poor stability in the human body. The broad aim of this research proposal is to develop a novel strategy that provides the ....There is huge interest in the development of bioactive peptides and proteins for the treatment of a wide range of diseases. However, there are still a number of hurdles that need to be overcome before this source of promising pharmaceuticals can fulfil their vast potential. One of the biggest challenges in the development of peptides and proteins as drugs is overcoming their poor stability in the human body. The broad aim of this research proposal is to develop a novel strategy that provides therapeutically promising peptides and proteins the ability to resist the body s natural degradation pathways so they are able to reach their biological target. To develop this strategy we will use the recently discovered peptide hepcidin as a model system. Hepcidin is the major iron-regulatory hormone in the human body and incorrect levels of this hormone result in either iron overload (haemochromatosis), when there is not enough hepcidin produced by the body, or anemia of inflammation when there is too much hepcidin. The development of hepcidin-based therapeutic agents to treat these conditions has the potential to have significant impact as it has been estimated that up to 1 in 300 Australians are affected by haemochromatosis during their lifetimes. Unfortunately, unmodified peptides, like hepcidin, are of limited therapeutic value due to their poor stability within the human body. This research proposal describes the development of stabilised hepcidin analogues with the potential of being useful drug leads for the treatment of haemochromatosis.Read moreRead less
Major Histocompatibility Complex (MHC) Genetics Of Ankylosing Spondylitis
Funder
National Health and Medical Research Council
Funding Amount
$568,612.00
Summary
Ankylosing spondylitis (AS) is the prototypic condition of a group of types of inflammatory arthritis called 'seronegative spondyloarthropathies'. These conditions are the most common form of inflammatory arthritis in white populations and occur worldwide. One third of the risk of developing AS is determined by genes within a region called the 'major histocompatibility complex' (MHC), in addition to the gene HLA-B27, the main gene causing AS. We aim to identify the remaining MHC genes.
Identification And Characterisation Of A Gene Causing Insulin Hypersecretion In A Mouse Model Of Diabetes Susceptibility
Funder
National Health and Medical Research Council
Funding Amount
$430,320.00
Summary
Diabetes is a disorder primarily characterised by the inability to produce and secrete the pancreatic hormone insulin, which regulates plasma sugar levels. This results in increased sugar levels which cause diabetic complications such as retinopathy and nephropathy. The inability to produce and secrete insulin is due to both defects in function as well as a reduction in pancreatic beta cells. Paradoxically it has been shown that some patients who are at risk of develping diabetes actually secret ....Diabetes is a disorder primarily characterised by the inability to produce and secrete the pancreatic hormone insulin, which regulates plasma sugar levels. This results in increased sugar levels which cause diabetic complications such as retinopathy and nephropathy. The inability to produce and secrete insulin is due to both defects in function as well as a reduction in pancreatic beta cells. Paradoxically it has been shown that some patients who are at risk of develping diabetes actually secrete more insulin than normal. Furthermore it has been suggested that this increase in insulin secretion actually may be associated with the decreased production and secretion of insulin characteristic of diabetes. The DBA-2 mouse is a model of reduced insulin production and secretion when exposed to high sugar levels or diabetes. However we have shown that in the normal non-stressed state DBA-2 mice actually secrete more insulin than normal and that this occurs from a very early age, suggesting that this trait is inherited. We have subsequently performed genetic studies and have identified a segment of DNA containing 10 genes associated with increased insulin secretion in DBA-2 mice. The level of one of these genes we have called Hip1 is increased 5-fold in DBA-2 mice, providing a candidate gene for increased insulin secretion in this model of diabetes susceptibility. However, whether Hip1 is also responsible for reduced insulin production and secretion in the DBA-2 mouse is not known. Therefore the overall hypothesis of this project is that the gene Hip1 which is associated with increased insulin secretion is also responsible for reduced insulin production and secretion when DBA-2 mice are exposed to high sugar or obesity. Determining why Hip1 is increased and whether it results in diabetes in DBA-2 mice may provide a reasonable candidate for the development of therapeutic interventions which may prevent the progression of diabetes in some patients.Read moreRead less
Investigation Of The Genetic Basis Of Insulin Hypersecretion In A Mouse Model Of Pancreatic Islet Failure
Funder
National Health and Medical Research Council
Funding Amount
$406,980.00
Summary
Type 2 diabetes is a chronic disease that is associated with blindness, kidney failure, heart attacks and stroke and these are secondary to high blood sugar levels. Thus, determining the cause of high blood sugar levels in type 2 diabetes will lead to better management of the disease and ease the financial burden on the public health system. High blood sugar in type 2 diabetes results from the inability of the body to secrete enough insulin. Insulin is the main hormone that lowers blood sugar le ....Type 2 diabetes is a chronic disease that is associated with blindness, kidney failure, heart attacks and stroke and these are secondary to high blood sugar levels. Thus, determining the cause of high blood sugar levels in type 2 diabetes will lead to better management of the disease and ease the financial burden on the public health system. High blood sugar in type 2 diabetes results from the inability of the body to secrete enough insulin. Insulin is the main hormone that lowers blood sugar levels and is produced by the pancreas. The reason for reduced insulin secretion in type 2 diabetes is not known. Paradoxically, it has been shown that some people who are at an increased risk of developing diabetes (eg people with obesity or a family history of diabetes) secrete more insulin than normal. It is not clear why this is, but a few studies have suggested that reducing insulin secretion in these circumstances can protect the pancreas and preserve its ability to secrete the appropriate amount of insulin. The DBA-2 is a mouse strain that like humans with type 2 diabetes, its pancreas can also fail to secrete the appropriate amount of insulin and under these circumstances becomes diabetic. Furthermore our laboratory has generated evidence that shows that like people who are at risk of diabetes, DBA-2 mice in fact secrete more insulin prior to becoming diabetic. Whether the cause of this increased insulin secretion is linked to the eventual reduction of secretion is not known. The aim of this study is to identify the gene that causes increased insulin secretion in the DBA-2 mouse. Furthermore, genetically manipulated animals will be produced that contain only this gene to determine its effect on insulin secretion. Should the identification of this gene be related to the eventual failure of the pancreas to secrete enough insulin, then it would provide a target for drug therapy to correct insulin levels and therefore reduce blood sugar levels.Read moreRead less
The Immunogenetics Of Ankylosing Spondylitis: A Genetic And Functional Investigation Of IL23R And Related Genes
Funder
National Health and Medical Research Council
Funding Amount
$536,679.00
Summary
Ankylosing spondylitis (AS) is a common inflammatory arthritis which causes primarily back pain and stiffness, and affects 1-250 individuals. Our group identified association between tagging genetic markers in the gene IL23R and AS, and our preliminary data suggests some related genes are involved as well. This study aims to identify the key genetic variants involved and determine the mechanism by which they cause AS.
Policing Australian Popular Music. This project will be the first comprehensive study of the relationship between policing and popular music in Australia. An interdisciplinary approach brings together criminology, music, history, social work, cultural, and music education research to investigate the processes by which certain forms of popular music and affiliated communities have been criminalised, and the ways musicians and musical communities have voiced resistance to police and state power. T ....Policing Australian Popular Music. This project will be the first comprehensive study of the relationship between policing and popular music in Australia. An interdisciplinary approach brings together criminology, music, history, social work, cultural, and music education research to investigate the processes by which certain forms of popular music and affiliated communities have been criminalised, and the ways musicians and musical communities have voiced resistance to police and state power. Through innovative interview and arts-practice based methodologies, the project will generate new knowledge on the historic and contemporary relations between state governance and creative cultural expression to inform policy and practice in policing as well as cultural investments. Read moreRead less
Molecular Imaging Of Brain Tumour Therapeutic Efficacy
Funder
National Health and Medical Research Council
Funding Amount
$412,200.00
Summary
The prognosis for malignant brain tumour patients that do not respond to intial treatment strategies is very poor. The fact that many of these patients patients will not survive longer than 12 months post diagnosis underscores the need to make treatment management decisions in a timely manner. This project seeks to develop and validate non-invasive early molecular imaging biomarkers that can quantify treatment efficacy months before traditional measures of efficacy are valid.
Hydrogen Bonding, Hydrogen Transfer, Hydrogenation and Hydrogenolysis: A Computational Quantum Chemistry Investigation. This proposal aims to carry out state-of-the-art chemistry research using computer modelling rather than traditional laboratory methods. The computer calculations are directed towards designing catalysts that will provide more efficient ways to convert environmentally harmful carbon dioxide to a valuable chemical fuel methanol, and to convert toxic polychlorinated hydrocarbon ....Hydrogen Bonding, Hydrogen Transfer, Hydrogenation and Hydrogenolysis: A Computational Quantum Chemistry Investigation. This proposal aims to carry out state-of-the-art chemistry research using computer modelling rather than traditional laboratory methods. The computer calculations are directed towards designing catalysts that will provide more efficient ways to convert environmentally harmful carbon dioxide to a valuable chemical fuel methanol, and to convert toxic polychlorinated hydrocarbon wastes to benign products. The increased understanding of free radicals that will stem from this research may ultimately help in dealing with problems associated with heart disease, some forms of cancer and vitamin B12 deficiency. New generations of chemists will be trained at the highest level in this burgeoning field of computational chemistry.Read moreRead less