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
Regulation And Mechanisms Of Cytotoxic Lymphocyte Function
Funder
National Health and Medical Research Council
Funding Amount
$631,010.00
Summary
The immune system is the essential complex barrier that protects the organism for infections and some malignancies. Despite considerable efforts, the mechanism by which immune cells kill dangerous unwanted cells is poorly understood. This project will investigate the mechanism of action and the role in human pathologies of a key component of the immune system, a toxic protein perforin.
Perforin is a cytolytic protein found in cytotoxic lymphocytes. It plays an essential role in the destruction of virus- and pathogen- infected cells as well as tumour cells. Perforin deficiency in humans and experimental animals results in the loss of resistance to many viral infections and dramatically increases the chance of spontaneous tumour formation. Whilst perforin was first characterised two decades ago, its mechanisms of action remain unknown. The current Grant Proposal will capitalise ....Perforin is a cytolytic protein found in cytotoxic lymphocytes. It plays an essential role in the destruction of virus- and pathogen- infected cells as well as tumour cells. Perforin deficiency in humans and experimental animals results in the loss of resistance to many viral infections and dramatically increases the chance of spontaneous tumour formation. Whilst perforin was first characterised two decades ago, its mechanisms of action remain unknown. The current Grant Proposal will capitalise on some recent key technological advances in our laboratory that are enabling us to investigate the mechanisms and the regulation of perforin function. Our recent advances in the field put us in a pre-eminent international position to conduct these studies. In broader terms, the proposed studies will have an immediate impact on our understanding of the mechanisms of cytotoxic lymphocyte regulated immune response and on immune homoeostasis in general. It will also improve our understanding of defence mechanisms against various pathogens and will provide more insight into the role of immune system in protection of the organism against cancer.Read moreRead less
The Adaptive Immune Response To Epstein-Barr Virus.
Funder
National Health and Medical Research Council
Funding Amount
$92,314.00
Summary
Epstein-Barr virus (EBV), the causative agent of glandular fever, is carried by a large proportion of adults worldwide. EBV is known to cause many cancers including Burkitt's lymphoma and has been linked to autoimmune diseases such as multiple sclerosis. The aim of this project is to find new fragments of EBV that the body's immune system can recognise and use to protect itself against the virus. Once found these pieces will form parts of the puzzle that will one day combine as a vaccine against ....Epstein-Barr virus (EBV), the causative agent of glandular fever, is carried by a large proportion of adults worldwide. EBV is known to cause many cancers including Burkitt's lymphoma and has been linked to autoimmune diseases such as multiple sclerosis. The aim of this project is to find new fragments of EBV that the body's immune system can recognise and use to protect itself against the virus. Once found these pieces will form parts of the puzzle that will one day combine as a vaccine against EBV.Read moreRead less
Identification And Characterisation Of Nessy; A Novel Gene Important For T Cell Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$250,500.00
Summary
This project aims to identify, and understand the function of, a new gene involved in the immune system. The Nessy mouse strain was developed in Prof. Goodnow s Medical Genome Centre at the Australian National University. It has a mutation in an unknown gene which causes a defect in T lymphocytes- white blood cells which are important for fighting infection. This project has three major aims: 1) to identify the gene. 2) to understand the defects in T lymphocytes caused by the gene. 3) to identif ....This project aims to identify, and understand the function of, a new gene involved in the immune system. The Nessy mouse strain was developed in Prof. Goodnow s Medical Genome Centre at the Australian National University. It has a mutation in an unknown gene which causes a defect in T lymphocytes- white blood cells which are important for fighting infection. This project has three major aims: 1) to identify the gene. 2) to understand the defects in T lymphocytes caused by the gene. 3) to identify which other genes interact with the mutant gene. Thus will allow us to understand how the mutant gene causes the T lymphocyte defects. This project will improve our understanding of the development and functioning of T lymphocytes, which play a central role in the immune system. Since the genomes of mice and humans are very similar, it is likely that we will be able to identify a human counterpart to the Nessy gene.Read moreRead less
Determining Regulators Of ILC3 In Mucosal Barrier Function And Immune Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$705,209.00
Summary
Innate lymphoid cells (ILCs) are specialized cells that defend the body against invading microorganisms at the body’s surfaces, mediate pathogen clearance and tissue repair but may also drive inflammatory conditions such as allergic asthma and inflammatory bowel disease. We will investigate the molecular switches that regulate this novel cell type and potentially uncover novel molecules or pathways for therapeutic targets.