CAGE: Consortium For The Architecture Of Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$501,080.00
Summary
This research project is about understanding why some people are most susceptible to disease than others, by identifying genetic factors that influence the expression of genes that are important in disease. We will work with leaders in the field in Europe and the USA in an international research consortium to find genetic variants with an effect on gene expression and to link those genetic factors to disease. The project will provide new understanding about the biological basis of common disease ....This research project is about understanding why some people are most susceptible to disease than others, by identifying genetic factors that influence the expression of genes that are important in disease. We will work with leaders in the field in Europe and the USA in an international research consortium to find genetic variants with an effect on gene expression and to link those genetic factors to disease. The project will provide new understanding about the biological basis of common diseases.Read moreRead less
Dynamics And Mechanisms Of Immune Complex-mediated Skin Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$526,467.00
Summary
Type III hypersensitivity underlies a number of common autoimmune diseases, including rheumatoid arthritis and lupus erythematosus. These diseases are caused by the deposition of immune complexes (IC) and the accumulation of neutrophils within small blood vessels. We will use real time imaging to dissect in space and time the recruitment of neutrophils and IC deposition during type III hypersensitivity reactions in order to better understand the pathogenesis of these conditions.
Methods And Software Tool For Complex Trait Analyses Using Multi-omics Data
Funder
National Health and Medical Research Council
Funding Amount
$573,999.00
Summary
This project aims to develop methods to disentangle the contribution of people’s difference in DNA sequence, DNA methylation, and gene expression to their difference in characteristics (including risks to diseases), and to utilise these information to predict disease risks of different people. This project also aims to develop a versatile and efficient computer software to implement the methods being proposed in this project, as well as all other commonly used methods in the research community.
We have discovered how a rare type of human antibody called IgG4 exerts a major regulatory influence on the body's immune system. We have discovered how IgG4 can "switch" off inflammatory white blood cells which has broad implications for the development of new forms of therapy for switching off allergies and autoimmune diseases and for switching on immunity to infections and cancers.
Identification Of Protein Altering Variants Influencing Preeclampsia Risk
Funder
National Health and Medical Research Council
Funding Amount
$572,014.00
Summary
Preeclampsia is a common and serious pregnancy disorder for which there is currently no early diagnostic test or cure other than delivery. It is also associated with later life cardiovascular disease. The identification of gene mutations for preeclampsia in this study will provide insight into the cause of this disorder that may lead to new treatments and tests to predict those women at risk.
Identifying Novel Susceptibility Loci For Osteoporosis Through Whole Genome Sequencing
Funder
National Health and Medical Research Council
Funding Amount
$623,969.00
Summary
Our highly successful genome-wide studies of bone mineral density (a risk factor for osteoporosis) have highlighted 60 loci relevant to the disease. However, a substantial amount of genetic variance remains unexplained. This project will focus on less common variants that have larger effect sizes and are relevant to osteoporosis, but are not well studied by approaches such as high-density SNP arrays and genome-wide association studies.
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.
Exome Sequencing By NGS To Identify Rare Variants Affecting Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$570,425.00
Summary
Rates of type 2 diabetes are rising dramatically, and current efforts are failing to stem its progression. More information about why the disease develops is urgently needed. We apply the latest technological innovations in DNA analysis to accelerate the discovery of the mechanism behind the development of type 2 diabetes. This knowledge will lead to new ways to control diabetes through development of novel therapies.
Estimation And Partitioning Of The Still-missing Heritability For Complex Disease
Funder
National Health and Medical Research Council
Funding Amount
$291,856.00
Summary
We have pioneered the use of multi-marker statistical genetic methods in human genetics to elucidate the genetic architecture of complex traits, including common diseases. We have shown that between a third and a half of additive genetic variation is captured by common genetic variants, leaving two-thirds to a half truly ‘missing’. In this proposal we will test our hypothesis that the still-missing heritability is due to low frequency causal variants. Applications of genomic medicine require thi ....We have pioneered the use of multi-marker statistical genetic methods in human genetics to elucidate the genetic architecture of complex traits, including common diseases. We have shown that between a third and a half of additive genetic variation is captured by common genetic variants, leaving two-thirds to a half truly ‘missing’. In this proposal we will test our hypothesis that the still-missing heritability is due to low frequency causal variants. Applications of genomic medicine require this fundamental knowledge to progress fully.Read moreRead less