New High-risk Variants For Colorectal Cancer: The Post-GWAS Era
Funder
National Health and Medical Research Council
Funding Amount
$710,105.00
Summary
Our aim is to discover new genes that greatly increase bowel cancer risk. If we can identify these carriers we may be able to prevent them getting cancer. By studying DNA related to bowel cancer, using a novel family design, we will identify families most likely to carry the new genes. We will focus genetic testing, using new techniques, to look for mutations in these prioritised families. Identified mutations will be tested in a 3,500 bowel cancer cases to see how important they are.
Biology Of EGFR Mutations In Glioblastoma Multiforme
Funder
National Health and Medical Research Council
Funding Amount
$287,445.00
Summary
The epidermal growth factor receptor (EGFR) is a protein that has a critical role in the development of normal cells. In glioma, the most lethal of the brain cancers, the EGFR is altered. These alterations result in uncontrolled activation of the EGFR, causing signals that promote the growth and survival of brain cancer. This grant seeks to understand the nature of the signals mediated by the altered EGFR, in turn helping us develop better therapeutics for the treatment of this deadly cancer.
Comprehensive Assessment Of Genetic And Environmental Risk Factors For Melanoma: A Population-based Family Study
Funder
National Health and Medical Research Council
Funding Amount
$150,679.00
Summary
Excessive sunlight can cause melanoma, a serious type of skin cancer. However, there are other factors including a person's genetic make-up that are thought to put some people at higher risk. Many 'healthy' people have small changes in their genes that might make them more likely to develop melanoma. We need to know more about these genetic factors. Our study will investigate how particular small genetic changes influence a person's likelihood of developing melanoma.
One of the current challenges in public health is to translate the progress from the Human Genome Project into reduced morbidity and mortality from disease. Once genetic defects are characterised, knowledge about the variability in severity of disease in mutation carriers, is important from a public health perspective. Hereditary Haemochromatosis (HH) is a common genetic disorder of iron overload that results in a wide spectrum of disease, varying from non-specific symptoms to severe damage to l ....One of the current challenges in public health is to translate the progress from the Human Genome Project into reduced morbidity and mortality from disease. Once genetic defects are characterised, knowledge about the variability in severity of disease in mutation carriers, is important from a public health perspective. Hereditary Haemochromatosis (HH) is a common genetic disorder of iron overload that results in a wide spectrum of disease, varying from non-specific symptoms to severe damage to liver, heart, pancreas and joints from iron deposition. It is easily treatable by regular blood donation, and population-based screening for HH has therefore been advocated. In this study we aim to address gaps in the existing data on HH regarding dietary and lifestyle factors that contribute to the variable clinical picture of HH. The study will be based on the Melbourne Collaborative Cohort Study, a cohort of 31,500 men and women who have been followed for approximately 10 years. Information on dietary and lifestyle factors was collected at initial enrollment, along with a blood specimen. We will test all non-Southern European participants (31,176) for the common HH mutations in the HFE gene and then select a subgroup of 1150 people, including all people with the main genetic defect as well as a comparison group, for further clinical followup. Participants will have genetic counselling and informed consent will be obtained. Participants will complete a short questionnaire and give a blood sample for measurement of iron overload, liver function, and other relevant blood tests, then undergo a brief clinical examination. Results of all tests will be given at a followup visit by genetic counsellor or physician. This study will provide important data on natural history of HH risk factors that influence variability in clinical presentation and the association of HFE mutations with chronic diseases and all cause mortality.Read moreRead less
Endocrine And Molecular Regulation Of Placental CRH Expression
Funder
National Health and Medical Research Council
Funding Amount
$466,980.00
Summary
Approximately 70% of infant death is associated with premature birth. Preterm birth occurs in 6-10% of pregnancies, and there has been no reduction in the rates of premature birth in the last 30 years. This is largely because we remain ignorant of how normal and abnormal birth is controlled. Understanding the physiology of human pregnancy is a critical step in the development of ways to detect and prevent preterm birth. Our group has demonstrated a link between production of a hormone (corticotr ....Approximately 70% of infant death is associated with premature birth. Preterm birth occurs in 6-10% of pregnancies, and there has been no reduction in the rates of premature birth in the last 30 years. This is largely because we remain ignorant of how normal and abnormal birth is controlled. Understanding the physiology of human pregnancy is a critical step in the development of ways to detect and prevent preterm birth. Our group has demonstrated a link between production of a hormone (corticotrophin releasing hormone, CRH) in the placenta and the length of time the baby is carried in the mother. In women who will deliver prematurely a rise in CRH occurs earlier in the pregnancy and more rapidly, while in women who deliver late the rise occurs more slowly. This work has given rise to the concept of a biological clock that determines the length of time the fetus will be carried by the mother before birth, and in which production of CRH in the placenta plays a central role. We have been studying how the CRH gene is controlled in placental cells. We have discovered some regions in the DNA of the CRH gene which have important roles in controlling how much CRH is made by the placenta. The experiments described in this research project will determine the molecular mechanisms that control the production of CRH in the human placenta. This will be done in two ways: (1) by examining the DNA sequences involved in controlling expression of the CRH gene and (2) by identifying the proteins that actually perform the regulating functions that result in either increased or decreased amounts of CRH being produced by the placenta. This important information will help us better understand how normal and abnormal birth is controlled, and from that knowledge new ways to detect and prevent premature birth can be invented.Read moreRead less
Cancer And Low-dose Radiation - Possible Effects Of CT Scans In Childhood
Funder
National Health and Medical Research Council
Funding Amount
$476,650.00
Summary
Despite 100 years of research there is uncertainty about effects of low dose radiation from background and medical X-rays. We will measure the incidence of cancer in Australians exposed to CT scans (medical X-rays) as children between 1985 and 2005. Our results, from follow-up to 2009, will show whether there is a small but signicantly increased risk of cancer and guide further improvement in radiation safety standards if these prove to be necessary.
Signalling Networks As Targets For Antibody Therapy In Glioma.
Funder
National Health and Medical Research Council
Funding Amount
$526,683.00
Summary
Antibodies are a major component of the bodies immune system that bind (i.e. stick) to foreign substances such as viruses. Once bound, these antibodies can activate other parts of the immune system, which help destroy the foreign substance. Analogous to the situation above, a number of institutions are testing antibodies that bind to cancer cells, in order to determine if they are able to destroy these cells. It is also possible to generate antibodies that bind to receptors on the surface of can ....Antibodies are a major component of the bodies immune system that bind (i.e. stick) to foreign substances such as viruses. Once bound, these antibodies can activate other parts of the immune system, which help destroy the foreign substance. Analogous to the situation above, a number of institutions are testing antibodies that bind to cancer cells, in order to determine if they are able to destroy these cells. It is also possible to generate antibodies that bind to receptors on the surface of cancer cells and block their function. If you target a receptor critical to the growth or survival of a cancer cell in this way, then swtiching-off this signal may inhibit tumor growth. In this proposal we plan to test a panel antibodies that recognize receptors important to the growth of brain cancer. Two of these antibodies have been generated and the other two will be made as part of this proposal. A key aspect of this proposal will be testing these antibodies in combination to determine how many receptors need to be targeted in order to get complete tumor regressions in animal models. Overall this work will help us identify new therapeutic strategies for the treatment of brain cancer. Finally, we will also analyze the way different receptors interact together in brain cancer cells.Read moreRead less
Role Of IGF Binding Protein-3 (IGFBP-3) And IGFBP-5 As Modulators Of Nuclear Hormone Signalling
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain ....The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain cells perform specialised functions. In test-tube experiments, IGFBP-3 and IGFBP-5 interact directly with the receptors that regulate the effects of these hormones. If the same thing happens inside the cell, IGFBP-3 and IGFBP-5 could change the way these receptors respond to signals from outside the cell. We will investigate what effect these IGFBPs have in living cells and in whole animals and how this may relate to human disease. If we are able to understand how IGFBP-3 and IGFBP-5 affect the way cells respond to vitamin A and D, then we may be able to develop new ways to treat certain human diseases.Read moreRead less
A Population-based Family Study Of Filaggrin Mutations And Allergic Disease Risk In Australia
Funder
National Health and Medical Research Council
Funding Amount
$308,584.00
Summary
It is biologically plausible that the association of known environmental risk factors for asthma may be different for genetically susceptible individuals. Few studies have examined the interaction between genetic and environmental factors. that have not considered genetic susceptibility are estimating an average risk of asthma across all genotypes in the population which may not be relevant for a particular sub-group.
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.