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
A Genome-wide Association Study In 2000 Glaucoma Cases With Matched Controls Using Equimoloar DNA Pools
Funder
National Health and Medical Research Council
Funding Amount
$610,267.00
Summary
Glaucoma is a common cause of loss of vision worldwide but we are unable to predict which people are at high risk of blindness. We aim to discover the genetic risk factors for glaucoma. We will use cutting edge genetic technology to assess the whole genome in thousands of patients with glaucoma. We hope to identify important new glaucoma genes, which could lead to the development of diagnostic tests and treatments which will provide the most cost-efficient ways to prevent glaucoma blindness.
Clinical Genetic Phenotyping Of Autism Spectrum Disorders
Funder
National Health and Medical Research Council
Funding Amount
$582,114.00
Summary
Individuals with autism spectrum disorders (ASD) have difficulty with communication, social interaction and intellectual disability. The cause is generally not known although most cases have a genetic basis involving multiple genes and possibly environmental factors. We will study families of children with ASD and carefully characterize features related to ASD in family members. This will help us to understand how ASD is inherited and serve as the basis for the discovery of autism genes.
Exposure To High Dose Estrogens In Adolescence: Long Term Effects On Mammographic Breast Density
Funder
National Health and Medical Research Council
Funding Amount
$89,050.00
Summary
Breast density is a well established risk factor for breast cancer, and has been shown to be reversibly influenced by hormone exposures in adult life. As one of the important roles of sex hormones during puberty is mammary cell proliferation, it is plausible that exposures at this earlier life stage might have a sustained influence on breast tissue composition and density, and subsequent breast cancer risk. This project aims to increase our understanding of the influence of sex hormones in adole ....Breast density is a well established risk factor for breast cancer, and has been shown to be reversibly influenced by hormone exposures in adult life. As one of the important roles of sex hormones during puberty is mammary cell proliferation, it is plausible that exposures at this earlier life stage might have a sustained influence on breast tissue composition and density, and subsequent breast cancer risk. This project aims to increase our understanding of the influence of sex hormones in adolescence on breast cancer risk by testing the hypothesis that exposure to large doses of sex hormones during adolescence has long-term effects on mammographic density. This will be done by comparing the mammographic densities of women who were treated with high doses of estrogen for tall stature during adolescence with women who were similarly assessed for tall stature but not treated. No previous study in humans has examined the long-term effects on breast tissue of high dose estrogen exposure at this early life stage. This is not surprising, given the difficulty in finding a suitable exposed population. This cohort of women, assessed or treated for tall stature, provides us with a unique opportunity to examine these influences. This research will add to our understanding of the influence of sex hormones in adolescence on mammographic density and breast cancer risk. If hormonal factors in adolescence are shown to influence mammographic density, this may lead to new avenues for breast cancer prevention efforts that are targeted much earlier in life. This information may lead to new research directions examining adolescent hormonal exposures (both endogenous and exogenous) and their influence on breast tissue.Read moreRead less
Determinant Spreading And The Role Of The MHC Class II Region In Systemic And Organ-specific Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$140,570.00
Summary
Autoimmune diseases are among the most important group of disorders affecting the adult population. In these diseases the immune system damages organs and tissues producing widespread pathology (systemic autoimmunity such as Lupus erythematosus) or localised disease (organ-specific autoimmunity such as insulin dependent diabetes). We understand very little about how and why the immune system attacks the body's own tissues. This study examines how antibodies and T lymphocytes are formed against c ....Autoimmune diseases are among the most important group of disorders affecting the adult population. In these diseases the immune system damages organs and tissues producing widespread pathology (systemic autoimmunity such as Lupus erythematosus) or localised disease (organ-specific autoimmunity such as insulin dependent diabetes). We understand very little about how and why the immune system attacks the body's own tissues. This study examines how antibodies and T lymphocytes are formed against components located inside cells of the body. The study involves genetically modifying mice by introducing key human genes which influence the development of autoimmunity. In this way the role of these human genes can be examined experimentally without having to work exclusively on patients. We also hope that these mice might be important in creating new models of celiac disease and insulin dependent diabetes. The proposed experiments should tell us how these genes contribute to the development of autoimmune disease. This understanding could be relevant devising treatments and interventions to prevent autoimmune diseases.Read moreRead less
Enhancing The Cardioprotective Effect Of Diadenosine Tetraphosphate: Designing Inhibitors Against Ap4A Hydrolase
Funder
National Health and Medical Research Council
Funding Amount
$442,500.00
Summary
Ischemia describes the condition where blood flow in the blood vessels of the heart is decreased or blocked, preventing delivery of oxygen and nutrients to the heart. Ischemic preconditioning is a phenomenon where short bursts of ischemia, followed by reperfusion, actually protect the heart from a subsequent longer period of ischemia. The biochemical signalling events involved in preconditioning are complex and incompletely defined, but most likely involve multiple pathways, although the mitocho ....Ischemia describes the condition where blood flow in the blood vessels of the heart is decreased or blocked, preventing delivery of oxygen and nutrients to the heart. Ischemic preconditioning is a phenomenon where short bursts of ischemia, followed by reperfusion, actually protect the heart from a subsequent longer period of ischemia. The biochemical signalling events involved in preconditioning are complex and incompletely defined, but most likely involve multiple pathways, although the mitochondrial ATP-dependent potassium channel may be in common with most pathways. Pretreatment with the compound diadenosine tetraphosphate (Ap4A) mimics ischemic preconditioning with noticeable reductions in tissue necrosis (cell death). This treatment has been shown in experimental work to protect the heart during periods of stress such as in heart surgery or recovery from an ischemic event. The biological site of action by Ap4A may be the mitochondria ATP-dependent potassium channel or an associated protein. Ap4A can be degraded by enzymes located inside and on the outside of heart cells, notably by two forms of Ap4A hydrolase. We will use antibody assays to understand the specific localization and amount of Ap4A hydrolase before and after ischemia and after ischemic preconditioning in human heart muscle and blood vessels. We propose to determine the structure of the enzyme and use novel computer methods to screen databases for potential inhibitors. These inhibitors of Ap4A hydrolase activity could aid the design of a potent inhibitor that would prevent Ap4A hydrolase from degrading Ap4A and therefore enhance the cardioprotective properties of Ap4A as well as minimizing side effects from the break down of Ap4A. We will also use these inhibitors and other known non-degradable Ap4A analogues in bioassays to test the relative significance of Ap4A hydrolase present in different cellular locations.Read moreRead less
A Case-control Study Of Environment And Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$808,948.00
Summary
Breast cancer is the most common cancer in Australian women and there have been a number of recent events which have raised public concern that occupational exposures are contributing to the increasing occurrence of this cancer. In this study, we will investigate occupational causes of breast cancer, particularly shift work, industrial solvent use and combustion products. We will compare occupations of 1000 women with breast cancer and 2000 women without cancer.
Markers Of Androgen Action, Genetic Variation And Prostate Cancer Risk
Funder
National Health and Medical Research Council
Funding Amount
$798,907.00
Summary
This proposal aim to follow up evidence from a number of studies that genetic and non-genetic markers of hormonal action in different periods of a man's life are associated with prostate cancer risk using a collection of three large, independent epidemiologic studies on prostate cancer named the Prostate Cancer Program. A principal objective is to collect exposure data on acne and digit ratio, and genotype cases and controls across the studies of the Prostate Cancer Program for common genetic va ....This proposal aim to follow up evidence from a number of studies that genetic and non-genetic markers of hormonal action in different periods of a man's life are associated with prostate cancer risk using a collection of three large, independent epidemiologic studies on prostate cancer named the Prostate Cancer Program. A principal objective is to collect exposure data on acne and digit ratio, and genotype cases and controls across the studies of the Prostate Cancer Program for common genetic variants in 4 candidate genes in the hormonal pathway. The established risk factors for prostate cancer are only age, race and family history. We anticipate that this project will cast light on the role of hormones in prostate cancer and that we will identify new markers of risk of prostate cancer and markers of disease aggressiveness. These outcomes will help us identifying men who are at risk for prostate cancer to target screening and surveillance, and plan prevention strategies. Furthermore, they will also form the basis for research on treatment targets.Read moreRead less
Evaluation Of An Instrument For Management Of Behavioural And Psychological Symptoms Of Dementia.
Funder
National Health and Medical Research Council
Funding Amount
$598,468.00
Summary
Behavioural and Psychological Symptoms of Dementia (BPSD) distress the patient and others. The behaviours, and not the underlying causes, are often treated with antipsychotics, despite side effects and low efficacy. An assessment instrument for care staff to determine and address causes of BPSD will be implemented. We predict training will reduce inappropriate prescribing and other reasons for distress. Where medication is required, detailed information will assist more targeted prescribing.
Finding The Genetic Causes Of Asthma: The Australian Asthma Genetics Consortium (AAGC)
Funder
National Health and Medical Research Council
Funding Amount
$1,697,639.00
Summary
Asthma is a major burden on individuals and health systems. Despite many decades of research, no major effective new treatments for asthma have emerged recently. We will establish a large international consortium to systematically test nearly all known human genes to identify those that influence asthma susceptibility. We expect to identify pathways not previously implicated in asthma and so lead to a potential breakthrough in the development of more effective treatments.