Human Arylamine N-acetyltransferase Regulation And Function - Effect Of Genetic Poymorphisms.
Funder
National Health and Medical Research Council
Funding Amount
$421,980.00
Summary
How we handle chemicals that enter our bodies depends on a series of enzymes that are responsible for breaking down the chemicals and eliminating them. The activity of many of these enzymes varies between individuals so our responses to chemicals and drugs is different for each individual. Some of the enzymes vary because of inherited mutations, but others vary because of the diets we eat and the environment in which we live. This project will investigate a major enzyme called acetlytransferase ....How we handle chemicals that enter our bodies depends on a series of enzymes that are responsible for breaking down the chemicals and eliminating them. The activity of many of these enzymes varies between individuals so our responses to chemicals and drugs is different for each individual. Some of the enzymes vary because of inherited mutations, but others vary because of the diets we eat and the environment in which we live. This project will investigate a major enzyme called acetlytransferase that has been implicated as a risk factor in diseases such as cancer, asthma, liver cirrhossis and adverse drug reactions. We plan to look at the enzyme in cells and determine what environmental factors contribute to its variation between individuals, and how this impacts on the genetic mutations that have been found in its gene. From these studies, we will have a much better undersanding of how different people metabolise foreign chemicals, and should be able to predict those most at risk of certain diseases.Read moreRead less
Neurogenic Mechanisms Of Cardiovascular Risk In The Metabolic Syndrome: Benefits Of Lifestyle Interventions
Funder
National Health and Medical Research Council
Funding Amount
$328,194.00
Summary
One in four adult Australians has the 'metabolic syndrome' (MetS), a clustering of metabolic and heart disease risk factors associated with abdominal obesity. Sympathetic nervous system (SNS) activity is increased in the MetS resulting in enhanced release of the stress hormone 'noradrenaline' . This project will examine the biological and genetic determinants of enhanced SNS activity and the benefits of lifestyle interventions (weight loss, weight loss maintenance and aerobic exercise).
Gene Variants In Adiponectin And Its Receptors As Risk Factors For Metabolic And Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$534,107.00
Summary
Obesity has a major impact on the development of metabolic syndrome (MetS), type 2 diabetes (T2D), and cardiovascular disease (CVD). It is important to identify the molecular links between obesity and these conditions. Adiponectin, an adipocyte-specific hormone, is a likely molecular candidate because of its pleiotropic metabolic actions. We will investigate the role of adiponectin, the variants within its gene ADIPOQ, and that of its two receptors, in the development of MetS, T2D, and CVD.
Identification Of Novel Genes Influencing Development Of Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$558,920.00
Summary
Type 2 diabetes is usually associated with obesity and is often part of a wider disturbance affecting an individual's energy metabolism. The number of affected people with type 2 diabetes has trebled since 1981 in Australia and is still increasing. Apart from individual suffering, this presents a major public health burden for the country (approx $3 billion annually). Currently available lifestyle based and pharmaceutical therapies are inadequate to control the increasing numbers of affected ind ....Type 2 diabetes is usually associated with obesity and is often part of a wider disturbance affecting an individual's energy metabolism. The number of affected people with type 2 diabetes has trebled since 1981 in Australia and is still increasing. Apart from individual suffering, this presents a major public health burden for the country (approx $3 billion annually). Currently available lifestyle based and pharmaceutical therapies are inadequate to control the increasing numbers of affected individuals. Unfortunately the cause of disease is poorly understood, although genetic factors are known to be important, in other words it runs in the family. This project proposes to identify some of these factors (genes) and how they contribute to the disease. Using molecular flags on the DNA (like DNA fingerprinting) we have previously found that a small region on chromosome 12 is likely to carry one or more of these disease genes. But there are over 100 genes in the region. To help choose the most likely candidates first for testing, we have developed an automated computer database searching program ranked the genes based on what is already known about them. We have also taken a large number of physiological measures in a large group of people. Some of these measures are controlled by the same chromosome 12 region - thus to improve our chances of finding the genes quickly we will look at those that change the most between people with diabetes and people without diabetes. In this project we shall investigate the 20 genes most likely affect diabetes based on changes in physiological measures and what is already known about them. A successful finding means we will know more about the mechanism of disease development and be able to better develop new therapies for treatment and prevention. If none of these genes are the culprit, we would continue examination of the next set of genes likely to be involved and so on until we are successful.Read moreRead less
The Interaction Of LPS Pathway Genes With Pre-natal And Early Exposure To LPS And Allergens Predicts Atopy At Age One
Funder
National Health and Medical Research Council
Funding Amount
$381,263.00
Summary
The poor understanding of the cause of asthma has made prevention strategies unsuccessful. This study will provide valuable data for understanding the interactions between exposure to environmental stimuli and LPS pathway genes on the development of allergy and asthma in infants. As environmental modifications and dietary interventions during pregnancy are being investigated, the findings from the proposed study will be important in guiding prevention practices of allergic diseases.
Liver Cell Transplantation For The Treatment Of Liver Based Metabolic Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$444,143.00
Summary
We propose to investigate the role of liver cell transplantation (LCT) for the therapy of inherited liver-based metabolic diseases using a methylmalonic aciduria (MMA) mouse model. LCT provides an exciting alternative to whole organ transplantation. Initially it was considered liver cells would be immunopriviledged. This has not proven to be the case. Immune modulation will be important. We will also examine immune modulation using antibodies to optimise longterm survival of allogeneic cells.
Functional And Genetic Analysis Of PHF11, A New Gene Associated With Atopic Dermatitis And Asthma
Funder
National Health and Medical Research Council
Funding Amount
$483,261.00
Summary
Atopic dermatitis, or eczema, is an increasingly common severe allergic condition affecting the skin that afflicts up to 30% of all Australian children. Eczema has significant financial impact on families as well on the health and well being of the affected child. The majority of asthmatics are also allergic, explaining why many children who suffer from eczema often go on to develop asthma as well. A familial history of asthma or eczema is an important risk factors for a child developing the dis ....Atopic dermatitis, or eczema, is an increasingly common severe allergic condition affecting the skin that afflicts up to 30% of all Australian children. Eczema has significant financial impact on families as well on the health and well being of the affected child. The majority of asthmatics are also allergic, explaining why many children who suffer from eczema often go on to develop asthma as well. A familial history of asthma or eczema is an important risk factors for a child developing the disorder, meaning that allergy is to a large extent determined by the genes we inherit from our parents. Our genes consist of four different building blocks, called nucleotides, which are identified by four letters: A, G, C and T. Each gene has a specific spelling of these four letters, although between any two people there will invariably be small single letter differences in the way a gene is spelt. Normally, these differences have no effect. In an allergic individual, however, these differences do have an effect. Identifying differences in the way a gene is spelt and why this should lead to eczema or asthma is a major research goal. In the past several years a number of genes have been identified that play an important role in allergy and we have recently identified a spelling difference in a new gene that we believe is important in the allergic response of eczema and asthma. At the moment, we can only guess how this gene might work. We know it is expressed in cells of our immune system that are important in allergy. We also suspect it might be an on or off switch for other genes important for allergy. This project will test these ideas and show how differences in the way this gene is spelt lead to differences in how this gene works. This will be important in adding another piece to the puzzle of how genes control allergy and could lead to better and earlier treatment of these disorders with improved health for affected children as well as adults.Read moreRead less