Novel Statistical Methods For Genetic Epidemiology
Funder
National Health and Medical Research Council
Funding Amount
$481,505.00
Summary
We are in the midst of a genomics revolution that is transforming epidemiology, medicine and drug discovery. However, the scarcity of sophisticated statistical techniques to deal with the complicated problems inherent in genetic investigations of complex diseases is currently the critical factor limiting the success of human gene discovery programs. Statistical genetic methodology is currently one of the fastest developing areas of epidemiology. In information-intensive' areas such as genetic ep ....We are in the midst of a genomics revolution that is transforming epidemiology, medicine and drug discovery. However, the scarcity of sophisticated statistical techniques to deal with the complicated problems inherent in genetic investigations of complex diseases is currently the critical factor limiting the success of human gene discovery programs. Statistical genetic methodology is currently one of the fastest developing areas of epidemiology. In information-intensive' areas such as genetic epidemiology, genomics, and proteomics, there is a high demand for data analysis and statistical skills. WA has some world class expertise in statistical science, both in academia and in industry. However, this expertise has not yet been applied in a system way to genetic data analysis. We propose to undertake advanced methodological research in statistical genetics and bioinformatics, to produce easy-to-use and accessible software tools and resources that allow methodological advances to be accessed by the Australian research community, and to apply our new methods and tools both to specific disease research and to the developing human genome epidemiology (HuGE) enterprise in WA. These new initiatives in methodological research will draw together a number of currently separate research strands and will provide new tools and resources that will allow applied Australian programs to improve the efficiency of their research into the causes of important. Methodological development in both bioinformatics and statistical genetics are recognized international areas of need.Read moreRead less
TSuNAMi: Time Series Network Animal Modelling. Our proposal is motivated by and based upon the successful representation of time series as a network (or graph). We construct an abstract representation of a system from measurements of its changing behaviour over time. Properties of that structure (the network) then allow us to infer diagnostic information of the system. Specifically, we propose to apply this to livestock welfare during transport. By measuring the biological and environment condi ....TSuNAMi: Time Series Network Animal Modelling. Our proposal is motivated by and based upon the successful representation of time series as a network (or graph). We construct an abstract representation of a system from measurements of its changing behaviour over time. Properties of that structure (the network) then allow us to infer diagnostic information of the system. Specifically, we propose to apply this to livestock welfare during transport. By measuring the biological and environment condition of the animal we construct a network representation of that system. Geometric features of that network can then be used to infer health or duress of the subject. This proposal will develop the generic mathematical machinery to connect geometric features of the network with system behaviour. Read moreRead less
Antigen Selection In The MHC-restricted Cellular Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$175,570.00
Summary
The body's white cells eliminate microorganisms through the actions of immune lymphocytes and other cells which conspire to kill and neutralise these unwanted guests. When microorganisms hide inside the cells of the body they are still detected by a set of T lymphocytes which have specific receptors for scrutinising the surface of cells for any changes which might signal an intracellular infection. The immune system is ever vigilant in its search for signs of infection which are generally appare ....The body's white cells eliminate microorganisms through the actions of immune lymphocytes and other cells which conspire to kill and neutralise these unwanted guests. When microorganisms hide inside the cells of the body they are still detected by a set of T lymphocytes which have specific receptors for scrutinising the surface of cells for any changes which might signal an intracellular infection. The immune system is ever vigilant in its search for signs of infection which are generally apparent when molecules called antigens are released by microorganisms and captured by the body's cells. This activates lymphocytes resulting in an immune response capable of eliminating the microorganisms. Scrutiny of the body's cells by lymphocytes occurs continuously even when there is no infection present in the body. Following infection of a cell, microbial antigens reveal the infection by their appearance on the cell surface where they are detected by the immune system's lymphocytes. This occurs through a mechanism called antigen presentation. During antigen presentation the proteins inside the cell, including those of any invading microorganism, are first degraded into shorter molecules called peptides. This event is called antigen processing. A fraction of the peptides created by antigen processing are captured by specialised receptors present on all cells. These receptors are called HLA or histocompatibility molecules. This project examines the molecular events which mediate the capture of peptide antigens by HLA molecules. The main focus is on those peptide antigens which elicit killer T cell responses by the immune system. A knowledge of how these peptides are selected for presentation and how they are captured and carried to the cell surface is fundamental to understanding immune responses to microorganisms, tumours, allergens, transplants and self tissues as in autoimmunity. Therefore the study is of great general relevance.Read moreRead less
Navigating tipping points in complex dynamical systems. This project aims to use applied mathematics to investigate the onset of tipping points in dynamical systems. Working with clinicians and practicing engineers, the project aims to contribute to the development of new treatment regimes for dynamical diseases and develop improved management strategies for resource focussed engineering industries. This should provide significant benefit to many areas, including the personalised treatment of di ....Navigating tipping points in complex dynamical systems. This project aims to use applied mathematics to investigate the onset of tipping points in dynamical systems. Working with clinicians and practicing engineers, the project aims to contribute to the development of new treatment regimes for dynamical diseases and develop improved management strategies for resource focussed engineering industries. This should provide significant benefit to many areas, including the personalised treatment of disease.Read moreRead less
Complex dynamical systems: inferring form and function of interacting biological systems. Often in biology a large number of simple parts interacting according to simple rules can result in behaviour that is rich and varied. This project aims to develop the mathematics of complex systems theory to describe how such collections of simple interacting parts can form large complicated structures, and to deduce what dynamical behaviour can result.
A Genome-wide Search For Genes Underlying The Developmental Origins Of Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,022,552.00
Summary
Epidemic rises in the incidence of many chronic diseases such as obesity, type 2 diabetes, hypertension, coronary artery disease and mental illness have occurred in Australia over the last two decades. Antenatal, early life and childhood factors have been consistently associated with the development of such diseases. We propose to conduct a genome-wide scan in an exceptional longitudinal birth cohort in order to identify the genetic mechanisms linking early life event and adult disease.
Unravelling the drivers of greenhouse gas emissions in estuaries. The aim of this project is to understand and quantify the factors controlling the emission of carbon dioxide, methane and nitrous oxide from estuaries. Coastal systems play a disproportionately large role in the global emissions of greenhouse gases, but this is poorly quantified. The project plans to use a combination of continuous concentration and stable isotope measurements, process measurements and advanced numerical modelling ....Unravelling the drivers of greenhouse gas emissions in estuaries. The aim of this project is to understand and quantify the factors controlling the emission of carbon dioxide, methane and nitrous oxide from estuaries. Coastal systems play a disproportionately large role in the global emissions of greenhouse gases, but this is poorly quantified. The project plans to use a combination of continuous concentration and stable isotope measurements, process measurements and advanced numerical modelling across a range of undisturbed to disturbed systems. It is intended that this project will provide information for conceptualising, calibrating and verifying models, including green-house gas production. Good models, and the data that support them, such as that provided by this study, are critical for the efficient allocation of management resources in Australian coastal systems, including by our partners. The findings from this project will have direct implications to the management, rehabilitation and protection of waterways (including biodiversity) in Australia.Read moreRead less
Postviral Wheezing In Childhood: Disregulation Of Airway Tone?
Funder
National Health and Medical Research Council
Funding Amount
$577,040.00
Summary
Asthma is a very common childhood condition that is becoming increasingly more common. Wheezing is common in infants and young children following viral infections and is often thought of as the first manifestation of asthma. However, many children and infants who wheeze with viral infections appear to grow out of asthma in their teenage years. Asthma that persists into adult life is usually associated with allergies to common environmental allergens, such as house dust mite and grass pollens. Ho ....Asthma is a very common childhood condition that is becoming increasingly more common. Wheezing is common in infants and young children following viral infections and is often thought of as the first manifestation of asthma. However, many children and infants who wheeze with viral infections appear to grow out of asthma in their teenage years. Asthma that persists into adult life is usually associated with allergies to common environmental allergens, such as house dust mite and grass pollens. However, many infants who wheeze with viral infections, especially in the first year of life, do not develop allergies in later life, raising the possibility that they did not have the same type of asthma as those whose symptoms persist. This project will study the effects of viral infections on lung function to determine whether particular types of virus can have detrimental effects of lung function lasting for years. We will also examine whether the age at which the infection occurs and the severity of the infection influence the long-term outcome. The project involves studying infants during the recovery phase of respiratory viral infections, older children years after documented infections and experimental animal models that have been infected under controlled conditions. By determining whether respiratory viral infections can have long-term effects on lung function that can mimic asthma, we will advance our understanding of how asthma develops. In addition, specific treatment and preventative strategies could then be developed to prevent these long-term abnormalities, instead of relying on asthma medication (especially inhaled corticosteroids) as is the current practice. Preventative strategies could include encouraging the development of specific vaccines.Read moreRead less
The Identification Of Thoracic Targets For Prevention And Intervention In Bronchopulmonary Dysplasia
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
The persistence of breathing problems from infancy to later life is a complication of premature birth with lifelong consequences. Breathing problems often occur together with lung disease, but prematurity can also affect heart and blood vessel development, and weakness of the main breathing muscle. We will find out how much the heart, lungs and diaphragm contribute to breathing problems in babies; helping us to better predict, diagnose and treat severe breathing problems in babies born preterm.
Backyard Bandicoots: Engaging community in urban bushland conservation. Backyard bandicoots: Engaging community in urban bushland conservation. This project aims to develop a model for urban ecosystem function and restoration, by identifying resources used by urban bandicoots (quenda). Digging mammal species turn over substantial volumes of soil as they forage for invertebrates, subterranean fungi, and plant material. These ecosystem engineers contribute to water infiltration, nutrient cycling, ....Backyard Bandicoots: Engaging community in urban bushland conservation. Backyard bandicoots: Engaging community in urban bushland conservation. This project aims to develop a model for urban ecosystem function and restoration, by identifying resources used by urban bandicoots (quenda). Digging mammal species turn over substantial volumes of soil as they forage for invertebrates, subterranean fungi, and plant material. These ecosystem engineers contribute to water infiltration, nutrient cycling, increased soil microorganism function, and seedling recruitment. They spread hypogeous mycorrhizal fungi that contribute to plant nutrition, crucial in Australia's nutrient-poor soils. This research is expected to improve targeted plantings in bushland reserves, and identify and mitigate threats to bandicoots in cities.Read moreRead less