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
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.
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
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
A Structural Investigation Into The T-cell Response To Epstein Barr Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$549,000.00
Summary
X-ray crystallography is an essential tool for solving the three-dimensional structure of proteins. Proteins control the biological processes within the cell and it is the precise shape of proteins that determines how they function. Depending on the particular sequence of the amino acids, the so-called building unit of the proteins, the protein molecule bends and forms a distinct, complex shape. This specific three-dimensional shape allows the protein to undertake its specific function, such as ....X-ray crystallography is an essential tool for solving the three-dimensional structure of proteins. Proteins control the biological processes within the cell and it is the precise shape of proteins that determines how they function. Depending on the particular sequence of the amino acids, the so-called building unit of the proteins, the protein molecule bends and forms a distinct, complex shape. This specific three-dimensional shape allows the protein to undertake its specific function, such as binding to other proteins, acting as an enzyme or interacting with nucleic acids. To determine how a protein acts, it is vital to know the precise three-dimensional shape at the atomic level. This proposal is concerned with understanding the precise shape of proteins that control the immune response to Epstein Barr Virus. Epstein Barr Virus is an ubiquitous human pathogen that has being linked to a number of cancers. This work will further our understanding of the immune response to Epstein Barr Virus.Read moreRead less
Antigen Presentation, Recognition And The Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$14,927,045.00
Summary
This program focuses on understanding the development of immunity during infection or inflammatory diseases using a broad array of techniques to dissect the function of various immune cell types and to explore the relationship between structure and function of important cell surface molecules. These studies will improve our ability to design new generation vaccines for combating infectious diseases, controlling cancer, or limiting autoimmune or inflammatory diseases.
Rapid mapping of genes for complex traits. This project will develop a new resource that will allow rapid identification of genes controlling complex traits. This world-leading resource will improve knowledge of diseases like diabetes and neurological diseases.
Evolution and the immune system: genetic differences in immune response between human populations due to adaptation to living in different geo-climatic locations. The project, which investigates the genetics of inter-population differences in immune response, will lead to advances in immunology and population genetics research, explain present population specific differences in disease incidence and possibly forecast future population trends of diseases such as asthma and allergy. The study will ....Evolution and the immune system: genetic differences in immune response between human populations due to adaptation to living in different geo-climatic locations. The project, which investigates the genetics of inter-population differences in immune response, will lead to advances in immunology and population genetics research, explain present population specific differences in disease incidence and possibly forecast future population trends of diseases such as asthma and allergy. The study will strengthen ties with collaborators around the world, thus promoting excellence in Australian research and gain Australia prestige in the international community as a country that produces research of global significance. Understanding the immune system's 'recent evolutionary roots' has implications for the health of Australians, especially in light of Australia's increasingly multi-ethnic background.Read moreRead less
Testing the costs and benefits of gene flow. The mixing of individuals from different populations has traditionally been viewed as beneficial because it maintains genetic variation and offsets the deleterious effects of inbreeding. However, this practice can also have detrimental effects on the fitness of populations. In this project field and laboratory experiments will test whether the benefits gained by mixing of individuals from different populations outweigh the costs or vice versa. In add ....Testing the costs and benefits of gene flow. The mixing of individuals from different populations has traditionally been viewed as beneficial because it maintains genetic variation and offsets the deleterious effects of inbreeding. However, this practice can also have detrimental effects on the fitness of populations. In this project field and laboratory experiments will test whether the benefits gained by mixing of individuals from different populations outweigh the costs or vice versa. In addition to providing information essential for the management of endangered species, the results will provide valuable insights on the processes that determine species' ranges and how new species evolve.Read moreRead less
Identifying the diversity and evolution of loci associated with adaptation to aridity/heat and salinity in ancient cereal crops. This project will use ancient grains of wheat, barley and rye to find 'lost' genetic diversity at key genes associated with resistance to aridity, salt and disease. This project will make the proteins of key genes, and study their interaction with the environment over time by measuring ions in the grains to reveal the ancient environmental conditions.