A National Case-Control Study Of The Causes Of Childhood Brain Tumours
Funder
National Health and Medical Research Council
Funding Amount
$1,159,259.00
Summary
Childhood brain tumours are the second most common childhood cancer (~20%) after leukaemia (~35%) and are the leading cause of cancer death among children. Children who survive a brain tumour are often left with physical and mental problems as a result of treatment. This can have a significant impact on the child, family and community. Greater understanding of the causes of childhood brain tumours may lead to preventative measures. Most children with brain tumours are very young, suggesting that ....Childhood brain tumours are the second most common childhood cancer (~20%) after leukaemia (~35%) and are the leading cause of cancer death among children. Children who survive a brain tumour are often left with physical and mental problems as a result of treatment. This can have a significant impact on the child, family and community. Greater understanding of the causes of childhood brain tumours may lead to preventative measures. Most children with brain tumours are very young, suggesting that factors to which parents are exposed may affect future children. For this reason, it is important to study the parents as well as the child. This study will investigate environmental exposures known to be harmful, such as parental cigarette smoking and exposure to pesticides and other chemicals. Such exposures are also thought to increase the risk of other childhood cancers like Acute Lymphoblastic Leukaemia. We will also investigate whether dietary factors - including vitamin supplements - in the parents or the child can reduce the risk of a child developing a brain tumour. This study also examines genetic factors which can influence the body's ability to deal with toxins. Some genetic variations, combined with diet and lifestyle factors, may alter the risk of developing some cancers. These interactions need to be examined in greater detail for childhood brain tumours. This national study will examine specific genes and analyse them in conjunction with rigorous assessment of exposures throught to be related to the development of childhood brain tumours. Results obtained from children with brain tumours and their parents will be compared with those from healthy 'control' children and their parents. This is the first study to assess gene-environment interactions in relation to the risk of childhood brain tumours.Read moreRead less
Generation Of Induced Pluripotent Stem (iPS) Cells And Their Potential Use In Periodontal Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$798,350.00
Summary
Dental diseases affecting the gums (periodontal diseases) are extremely prevalent. The effects of periodontal disease can be particularly severe as loss of support for the teeth leads to loose teeth and severely compromised chewing function. If left untreated, the associated loss of function may necessitate extraction of the teeth. We propose to generate induced pluripotent stem cells from gums and explore whether they can be used to restore periodontal tissues damaged by periodontal disease.
The Significance Of Aeroallergens In Eosinophilic Esophagitis
Funder
National Health and Medical Research Council
Funding Amount
$117,331.00
Summary
Eosinophilic esophagitis is an allergic condition that causes difficulty swallowing food and chest discomfort.Current diagnostic methods are inaccurate, and treatments are not curative. This project aims to clarify the role of promising new diagnostic techniques and to delineate the significance of aeroallergens (e.g. pollens) with a view to improving the treatment of eosinophilc esophagitis in the future. It is possible that simply avoiding pollens or treating hayfever in the future may be all ....Eosinophilic esophagitis is an allergic condition that causes difficulty swallowing food and chest discomfort.Current diagnostic methods are inaccurate, and treatments are not curative. This project aims to clarify the role of promising new diagnostic techniques and to delineate the significance of aeroallergens (e.g. pollens) with a view to improving the treatment of eosinophilc esophagitis in the future. It is possible that simply avoiding pollens or treating hayfever in the future may be all that is required to manage this condition.Read moreRead less
The Role Of The Osteoblast In Mediating Glucocorticoid-Induced Metabolic Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$825,254.00
Summary
Glucocorticoids (GC) exceed most other drugs in terms of numbers of patients treated and indications. Preventing or attenuating the deleterious effects of GC on fuel metabolism is therefore of great clinical significance. Our studies will create new knowledge regarding the mechanisms of GC-induced diabetes and osteoporosis, and will contribute to the development of new approaches that are essential to tackle the pressing medical problem of GC-induced disease.
Dissecting The Role Of The Adipokine Leptin In Control Of The Inflammatory Response To Helicobacter Pylori
Funder
National Health and Medical Research Council
Funding Amount
$569,063.00
Summary
Helicobacter pylori is a bacterium that causes chronic gastric inflammation (gastritis), which may lead to cancer. Approximately 20% of Australians are infected. As part of the search for a human vaccine, we are attempting to understand the immune response against this bacterium. This study will investigate a novel observation that adipokines-small proteins produced by fat cells can regulate the actions of immune cells in the stomach and in this way determine whether vaccination works.
Mechanisms Of Nanoparticle-mediated Inhibition Of Asthma
Funder
National Health and Medical Research Council
Funding Amount
$637,921.00
Summary
Ultrafine pollution particles may promote asthma, and there is concern that man-made 'nanoparticles' have a similar effect. Surprisingly, we found that inert toxin-free nanoparticles inhibit asthma. We propose nanoparticles do this by leaving a unique �imprint� in the lung. We will explore how this imprint modifies lung inflammatory and immune regulatory cell function, and investigate particles made from advanced biodegradable polymers as potential therapeutics for inflammatory lung diseases suc ....Ultrafine pollution particles may promote asthma, and there is concern that man-made 'nanoparticles' have a similar effect. Surprisingly, we found that inert toxin-free nanoparticles inhibit asthma. We propose nanoparticles do this by leaving a unique �imprint� in the lung. We will explore how this imprint modifies lung inflammatory and immune regulatory cell function, and investigate particles made from advanced biodegradable polymers as potential therapeutics for inflammatory lung diseases such as asthma.Read moreRead less
Mitochondrial Dysfunction And Pathways Of Cell Death In Drug-induced Liver Injury
Funder
National Health and Medical Research Council
Funding Amount
$301,650.00
Summary
Drugs are an important cause of liver disease that can result in fatal liver damage or require liver transplantation. More than 500 drugs are reported to cause liver disease, but we know almost nothing about how drugs injure the liver. As well as prescribed drugs: panadol, either after self-poisoning or inadvertently taken in too high a dose in someone who is not eating or is taking other medications that interfere with panadol breakdown, is one of most common causes of acute liver failure. Furt ....Drugs are an important cause of liver disease that can result in fatal liver damage or require liver transplantation. More than 500 drugs are reported to cause liver disease, but we know almost nothing about how drugs injure the liver. As well as prescribed drugs: panadol, either after self-poisoning or inadvertently taken in too high a dose in someone who is not eating or is taking other medications that interfere with panadol breakdown, is one of most common causes of acute liver failure. Further, several herbal medicines have been implicated as causing liver disease. This project is designed to help us understand why and how 3 particular drugs damage the liver. We will study panadol, diterpenoids the active ingredients of skullcap, a herbal medicine, and azathioprine (imuran), a drug commonly used to suppress rejection after kidney or liver transplantation which occasionally causes very severe liver disease. Our main hypothesis is that these drugs damage mitochondria, the energy generating structures that form the engine of all living cells. We already know a little about how drug metabolites of panadol and the diterpenoids can damage mitochondria, but no-one has proven that this is the most important way in which they damage the liver. For drugs like azathioprine in which liver damage is rare, we are proposing that genetic defects in the mitochondrial DNA are what could predispose to liver injury. Thus our measurements will include how much mitochondrial DNA damage is caused by the drugs. Panadol, diterpenoids and azathioprine cause liver cell death by differing pathways (called apoptosis and necrosis). There are plausible ways in which mitochondrial damage could start off either (or both) cell death pathways during drug-induced liver injury, and we plan to test these. The new knowledge gained about how drugs damage the liver will be instrumental in allowing us to design new approaches to treat this important problem.Read moreRead less
Clinical Modulation Of The Hyperglycaemic Effect Of A 10-second Sprint In Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$567,207.00
Summary
Although regular exercise provides a number of health benefits for individuals with Type 1 diabetes, it increases the risk of hypoglycaemia, which if severe can result in convulsion, coma and irreversible brain damages. Recently, we have made the surprising discovery that it is possible to prevent hypoglycaemia if exercise is combined with one or several short sprints. Our goal is to identify some of the clinical factors likely to interfere with the glucoregulatory benefits of sprinting.
Dendritic Cell Function, Migration And Modulation In A Murine Model Of Inflammatory Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$201,870.00
Summary
Rheumatoid arthritis (RA) is a debilitating disease that affects the joints and other tissues. While it can often be controlled with drugs, complete remission off treatment is rare. Dendritic cells are the educators of the immune system. By displaying antigen to T cells they communicate the response that the immune system should make to foreign organisms, tumors and to self. Therefore, a communication failure may result in chronic inflammation, tumor growth or autoimmune disease, such as RA. In ....Rheumatoid arthritis (RA) is a debilitating disease that affects the joints and other tissues. While it can often be controlled with drugs, complete remission off treatment is rare. Dendritic cells are the educators of the immune system. By displaying antigen to T cells they communicate the response that the immune system should make to foreign organisms, tumors and to self. Therefore, a communication failure may result in chronic inflammation, tumor growth or autoimmune disease, such as RA. In this proposal, we focus on the role of dendritic cells in a mouse model of RA and explore ways of using dendritic cells to turn off disease, that if successful may translate in humans to induction of remission.Read moreRead less
Understanding The Role That Cellular Hypoxia Plays In Normal Heart Development
Funder
National Health and Medical Research Council
Funding Amount
$522,773.00
Summary
Congenital heart defects (CHD) are the most common type of birth defects, being present in 6 out of every 1000 live births, and 10% of stillbirths. In addition to the danger of death during childhood, such heart defects also increase the risk of heart disease during adulthood. Our research project involves looking for the genetic causes of CHD. We are looking at two genes , called HIF1a and CITED2, for which we already have evidence that they are very important in allowing the heart to form norm ....Congenital heart defects (CHD) are the most common type of birth defects, being present in 6 out of every 1000 live births, and 10% of stillbirths. In addition to the danger of death during childhood, such heart defects also increase the risk of heart disease during adulthood. Our research project involves looking for the genetic causes of CHD. We are looking at two genes , called HIF1a and CITED2, for which we already have evidence that they are very important in allowing the heart to form normally within the embryo. Because the heart is the first organ to form in the embryo (during the first trimester), we cannot use humans to study this process. Instead we have two lines of mice which specifically lack either the HIF1a or CITED2 genes throughout the embryo. Both of these mouse lines have severe heart defects similar to some types of CHD seen in humans. However, removal of either of these genes also causes severe defects in other tissues, complicating our study. To overcome this problem, we will use a slightly different technique to remove either gene specifically in the entire developing heart of the embryo, while leaving the normal gene in the rest of the embryo. Thus we will be able for the first time to study the effects of these genes on the heart alone. We suspect that the defects in the hearts of such embryos will be of a particular sub-type of CHD. If this is true, in the future we hope to be able show that mutation of either of these genes will cause a specific type of human CHD. This will enable genetic screening of families with a history of CHD, assist in genetic counselling, and promote the development of therapies.Read moreRead less