Diet As A Therapeutic Target In Depression: A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$498,564.00
Summary
Depression is predicted to become the second-most common cause of disability in the world by 2020. While there is now compelling new evidence to suggest that diet plays an important role in the risk for and the genesis of depression, there are no existing data regarding the impact of dietary improvement on existing depressive illness. The aim of the proposed study is to answer the critically important and frequently asked question "If I improve my diet, will my mental health improve?"
AusGDB-Depression: An Australian Genetic Database Study Of Functional Genetic Variants And Environmental Factors In Major Depression
Funder
National Health and Medical Research Council
Funding Amount
$620,486.00
Summary
Major depression is the leading cause of disability in Australia, but its causes are unknown. Despite a significant role of genes in this disorder and many genetic studies, researchers have not been able to identify the genes that increase the risk for this disorder. In this project, we will identify, characterize and use genetic functional variants and environmental factors to create a way to predict diagnosis of this disorder.
Analysing Genetic And Environmental Risk Factors And Their Interactions For Common Cancers And Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$129,937.00
Summary
The statistical models for analysing cancer and cardiovascular risk factor family data are important for understanding the genetic and environmental aetiology of these diseases, but complicated by the different levels of correlations between relatives in a family. The conventional assumption of independence in observations is invalid in these situations. We intend to develop, test, implement and distribute a comprehensive suite of new statistical methods designed specifically to assistant molecu ....The statistical models for analysing cancer and cardiovascular risk factor family data are important for understanding the genetic and environmental aetiology of these diseases, but complicated by the different levels of correlations between relatives in a family. The conventional assumption of independence in observations is invalid in these situations. We intend to develop, test, implement and distribute a comprehensive suite of new statistical methods designed specifically to assistant molecular geneticists and genetic epidemiologists undertake informative and meaningful analyses of the measured and latent genetic and environmental risk factors and their possible interactions. The two associate investigators, Prof John Hopper and Prof Stephen Harrap, will bring their respective genetic epidemiological and biometric statistical expertise and their prestigious family data resources to this project. With the suite of flexible statistical models and analyses, we will further our knowledge about genetic and environmental risk factors and their interactions of common cancers and major gene effects for cardiovascular phenotypes. Simulation studies will help us understand some phenomena accounted in the research but cannot be replicated in reality and assess the efficiency of the statistical methods and credibility of our analysis results independently. Statistical programs developed in this project can also be used in other genetic and epidemiological studies (e.g. diabetes, epilepsy) where such high-level statistical tools are not yet available.Read moreRead less
Characterisation Of Susceptibility To Abacavir Hypersensitivity Carried On The HLA-B-5701, -DRB*07 And -DQ3 Haplotype
Funder
National Health and Medical Research Council
Funding Amount
$545,250.00
Summary
Drug hypersensitivity reactions (HSR) are a significant iatrogenic cause of morbidity, and even of mortality. Unfortunately the underlying mechanisms are poorly understood, making it difficult to predict which individuals may be at risk of these reactions. Research indicates that the interaction between specific drugs and the host immune system in HSR is similar to that observed in transplantation and that the major histocompatibility complex (MHC) region of the human genome assumes importance i ....Drug hypersensitivity reactions (HSR) are a significant iatrogenic cause of morbidity, and even of mortality. Unfortunately the underlying mechanisms are poorly understood, making it difficult to predict which individuals may be at risk of these reactions. Research indicates that the interaction between specific drugs and the host immune system in HSR is similar to that observed in transplantation and that the major histocompatibility complex (MHC) region of the human genome assumes importance in this setting, as it does in determining if a transplanted organ is 'rejected' or 'accepted'. We have identified a striking association between MHC genetic markers (HLA-B*5701, -DRB1*0701, and -DQ3) and HSR to the HIV drug abacavir. Carriage of these markers was found in 72% (13-18) of individuals with this reaction, and 0% (0-185) of those who tolerated abacavir (odds ratio 822), thus predicting HSR in 100% of cases, and abacavir tolerance in 97%. This represents one of the most powerful MHC gene associations with a clinical syndrome yet described. As abacavir HSR affects ~5% of abacavir users, knowledge of these genetic factors would be predicted to significantly reduce the risk of susceptible individuals developing HSR, without inappropriately denying access to abacavir. This association between the MHC and abacavir HSR in the clinical setting provides a unique opportunity to characterise mechanisms that underlie this HSR, which may give insights into drug HSR generally. Continued support of this research in the public domain, rather than in the commercial sector, will ensure that commercial considerations do not restrict the dissemination of these findings. Given the high predictive value of this readily performed genetic test in identifying at-risk individuals, there is also a clinical imperative to rapidly identify the gene(s) involved, to provide the most targeted risk assessment possible.Read moreRead less
An Investigation Of The Role Of Gene-environment Interactions And Epigenetics In Depression: Nature Combined With Nurture.
Funder
National Health and Medical Research Council
Funding Amount
$337,602.00
Summary
Depression is one of the biggest public health problems, yet the causes remain largely unknown. This study aims to determine how environmental factors can combine with particular genes to increases an individual’s risk of depression. Environmental factors can also cause modifications to genes which can affect an individual’s health. This study will thus also examine whether women with post-natal depression and their children have different gene modifications than those without depression.
Microarrays are a new technology for measuring the relative expression levels of thousands of genes simultaneously. They allow medical researchers to take a genome-wide look at which genes are active in a particular tissue type in an organism at a particular time. Many biomedical and biological research groups in Australia have recently untaken microarray experiments for the first time or are planning microarray experiments in the near future. Microarray experiments produce massive amounts of in ....Microarrays are a new technology for measuring the relative expression levels of thousands of genes simultaneously. They allow medical researchers to take a genome-wide look at which genes are active in a particular tissue type in an organism at a particular time. Many biomedical and biological research groups in Australia have recently untaken microarray experiments for the first time or are planning microarray experiments in the near future. Microarray experiments produce massive amounts of information and the study of how to extract this information is still in a fledgling state. This project will solve a number of fundamental problems in microarray data analysis. The emphasis is not on special methods of down-stream analysis but on basic issues which are common to all microarray experiments. The project will determine how tissue samples from different organisms should be combined in complex experiments. It will develop methods for evaluating the quality of results from microarray experiments. It will make microarray analysis less sensitive to production artifacts. It will make novel use of serial analysis of gene expression (SAGE), a more accurate but more expensive and less available technology, to calibrate the results of microarray experiments. The results will be applied during the lifetime of the project to a number of experiments at the Walter and Eliza Hall Institute and the University of Melbourne on blood cell development, cell growth and proliferation, resistance to malaria and leishmaniasis parasites, and Down syndrome.Read moreRead less
Identifying Determinants Of Both The Origins And The Progression Of The Depressive And Bipolar (mood) Disorders.
Funder
National Health and Medical Research Council
Funding Amount
$6,235,352.00
Summary
Currently, mood disorders are classified by severity, largely ignoring causes and leading to limited treatments. The Team will clarify how differing depressive and bipolar (mood) disorders are best modelled and pursue their differing causes, so assisting identification of specific treatments relating to their underlying causes. Our studies employ a range of sophisticated technologies, including molecular biology, brain imaging techniques, and mathematical modeling. The capacity of such research ....Currently, mood disorders are classified by severity, largely ignoring causes and leading to limited treatments. The Team will clarify how differing depressive and bipolar (mood) disorders are best modelled and pursue their differing causes, so assisting identification of specific treatments relating to their underlying causes. Our studies employ a range of sophisticated technologies, including molecular biology, brain imaging techniques, and mathematical modeling. The capacity of such research to advance the management of mood disorders address a pressing clinical need.Read moreRead less
The Role Of Non-classical MHC Class I Molecules In Adaptive Immunity
Funder
National Health and Medical Research Council
Funding Amount
$443,834.00
Summary
Specialised proteins called MHC class Ia molecules (MHC-Ia) stimulate killer T cells to lyse virus infected cells. In contrast, the function of the closely related MHC-Ib is uncertain. Recent findings have demonstrated that MHC-Ib can also be recognised by T cells and this interaction is important in the control of viral infections. However, despite the similarity to MHC-Ia, it is unclear how this interaction occurs. This project aims to investigate how killer T cells recognise MHC-Ib molecules.