Fine Mapping Of Genes Underlying Asthma And Eosinophilia
Funder
National Health and Medical Research Council
Funding Amount
$278,000.00
Summary
Asthma is the fourth most common chronic disease in Australia, and is increasing in incidence. Genetic factors are known to be important modifiers of disease risk, and several genes have been reported in the literature as being involved in either causing asthma or altering response to therapy. Immunoglobulin E (IgE) level and eosinophil count are two factors known to be increased in the blood of asthmatics. In two studies by our group, one of asthma in families, the other of healthy adolescent t ....Asthma is the fourth most common chronic disease in Australia, and is increasing in incidence. Genetic factors are known to be important modifiers of disease risk, and several genes have been reported in the literature as being involved in either causing asthma or altering response to therapy. Immunoglobulin E (IgE) level and eosinophil count are two factors known to be increased in the blood of asthmatics. In two studies by our group, one of asthma in families, the other of healthy adolescent twins, we showed these measures to be genetically linked to two different regions in the genome. Closer examination of these regions found several genes that might be responsible for the linkage. In the present study, we plan to test which of these candidate genes actually causes elevated IgE level or eosinophil count. The approach is to compare the frequency of a putative gene in a child expressing that phenotype to that in their parents. Each child receives one copy of a gene from the father, and one from the mother, making up a complete genotype (two possibly different versions or alleles of the gene). Since each parent transmitted only one allele to the child, the remaining allele from each parent can be used to create a normal control genotype, that is guaranteed to come from the same ethnic background as the asthmatic child. Therefore, we will collect replacement blood samples in those familes where all the previously DNA has been used up in our earlier study. We will extract DNA, and measure the genotypes of parents and children at the 6 genes in our two regions that we think most likely to be involved in eosinophil count or IgE level. This family based test will allow us to decide which genes are genuinely associated with asthma in our population. We will also test if these genes interact with other genes thought to be asthma risk factors. Identification of novel genes involved in asthma will help understand and ultimately treat this condition.Read moreRead less
Structural Studies On The Immune Effector Perforin: Developing Mechanism-based Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$1,116,594.00
Summary
Perforin is an essential weapon deployed by the human immune cells in order to destroy virally infected or cancerous cells. Despite this key role, unwanted or excessive perforin function can result in disease and can severely impact on successful treatment of leukaemia through bone marrow transplantation. This application aims to understand the molecular details of perforin function, and to apply this knowledge to develop perforin inhibitors.
Localisation Of Genes For Multiple Sclerosis In The HLA Region
Funder
National Health and Medical Research Council
Funding Amount
$426,500.00
Summary
Multiple sclerosis (MS) is a disease that affects around 10,000 Australians. It is a disease of young adults with women being affected more often than men. While there are therapeutics available to treat it, these are very expensive ($10-12,000 per annum) and are effective in only a proportion of affected individuals. MS is governed by a complex interplay of environmental and genetic susceptibility factors, neither alone sufficient to cause disease, however, the study of these factors has been c ....Multiple sclerosis (MS) is a disease that affects around 10,000 Australians. It is a disease of young adults with women being affected more often than men. While there are therapeutics available to treat it, these are very expensive ($10-12,000 per annum) and are effective in only a proportion of affected individuals. MS is governed by a complex interplay of environmental and genetic susceptibility factors, neither alone sufficient to cause disease, however, the study of these factors has been confounded by the complex nature of the disease. We and other researchers have identified the human leukocyte antigen (HLA) complex on chromosome 6 as harbouring susceptibility genes for MS. Our recent work has localised these genes in two distinct regions of the HLA complex. In this project we plan to localise these genes more precisely to permit their identification. By identifying these genes we hope to develop an understanding of their function in a healthy person and in a person with MS. Understanding what goes wrong during disease is a critical first step along the track to the design of novel therapeutics. A successful therapeutic agent would be designed to interfere with disease processes and treat the disease more effectively.Read moreRead less
I am a clinical researcher determining: a) the role of altered airway structure, particularly airway smooth muscle and extracellular matrix, in asthma and COPD; and b) the prevalence of, and risk factors for, respiratory disease in general populations.
Developing And Applying Biologically Plausible Statistical Models For Normal And Non-normal Family Data
Funder
National Health and Medical Research Council
Funding Amount
$339,700.00
Summary
Although molecular and computing advances have enabled more detailed investigations of inherited diseases and the ability to fit realistic statistical models to these data, limitations still exist when analysing family data. Often only basic statistical analyses are performed, due to the lack of understanding of complexities within the data and-or inability of researchers to fit appropriate statistical models. These factors have hampered the search for genes and environmental factors influencing ....Although molecular and computing advances have enabled more detailed investigations of inherited diseases and the ability to fit realistic statistical models to these data, limitations still exist when analysing family data. Often only basic statistical analyses are performed, due to the lack of understanding of complexities within the data and-or inability of researchers to fit appropriate statistical models. These factors have hampered the search for genes and environmental factors influencing common diseases. This project aims to develop novel, biologically realistic statistical models for investigation of common, complex diseases, such as heart disease and cancer, in families. These models will incorporate both measured and unmeasured genetic and environmental factors, and will be applicable to both normally distributed and non-normally distributed traits. Model fitting will use computer-intensive simulation techniques. Application of the models to data from two large pre-existing studies of international renown, the Victorian Family Heart Study and the Australian Prostate Cancer Family Study, will enable a better understanding of the genetic and environmental factors influencing heart disease and cancer. The models will also be applicable to many other studies of diseases which use data from families, and allow more accurate and useful information to be obtained from data. Software will also be made freely available to other researchers. This will ultimately translate into better outcomes from familial genetic research, and eventually, better prevention, detection, and treatment of the diseases.Read moreRead less
Preventive messages and guidelines to reduce sitting — especially prolonged periods of sitting — have emerged. However, what prolonged sitting should be replaced with, and the feasibility of making real world changes to this behaviour, is unknown. This program of research will provide high quality evidence on the benefits of reducing prolonged sitting time, and the effectiveness and acceptability of achieving sitting reductions in real-world contexts.