Environmental Risk Factors For Iron Overload-related Disease In A Cohort Study Of Hereditary Haemochromatosis
Funder
National Health and Medical Research Council
Funding Amount
$152,936.00
Summary
Results published last year from our Melbourne HealthIron study of hereditary haemochromatosis (iron overload disease) show that almost one third of the 50,000 men genetically at risk of iron overload in Australia will develop symptoms of disease including fatigue, arthritis and liver damage. We will use data from the recent follow-up of the Health2020 cohort, of which HealthIron is a sub-study, to determine environmental risk factors for progression to disease in people with iron overload.
Germline Mutations In Mismatch Repair Genes: Prevalence, Risk Of Cancer, And Environmental Modifiers Of Risk.
Funder
National Health and Medical Research Council
Funding Amount
$216,750.00
Summary
Aims: 1. Develop a model that will predict who has a mutation in a group of genes that cause cancer 2. Estimate risk of cancer in people who have a mutation in these genes (carriers) 3. Determine if cancer risk in carriers can be reduced People who inherit a mutation in a group of genes called 'mismatch repair genes' are at increased risk of cancer, particularly cancer of the colon and rectum. If these carriers can be identified they can take preventive measures such as screening to reduce their ....Aims: 1. Develop a model that will predict who has a mutation in a group of genes that cause cancer 2. Estimate risk of cancer in people who have a mutation in these genes (carriers) 3. Determine if cancer risk in carriers can be reduced People who inherit a mutation in a group of genes called 'mismatch repair genes' are at increased risk of cancer, particularly cancer of the colon and rectum. If these carriers can be identified they can take preventive measures such as screening to reduce their risk of cancer and death. We will develop a model using data from the Colon Cancer Family Registry (CFR), the world's largest dataset of carriers and non-carriers which has already recruited and genetically tested over 4,000 families from Australasia, USA and Canada. The model will allow clinicians to predict who is a likely be a carrier based so they can be tested for the mutation. We know the risk of cancer is high in carriers, but we don't have precise estimates. We will use the Colon CFR applying sophisticated statistical methods required to answer this question. This data is critical for genetic counselling so appropriate decisions can be made by the patient and the doctor as to what preventive measures to take. We will also use the Colon CFR data to find out what how the carriers who develop cancer differ from those who stay cancer free using their completed lifestyle questionnaires which includes questions on diet, smoking, alcohol consumption, exercise, aspirin use, and oral contraceptive pill use. We may identify risk factors that carriers can avoid (or take up if they reduce cancer risk) to reduce their risk of cancer.Read moreRead less
Projection Of The Impact Of Climate Change On The Transmission Of Ross River Virus Disease
Funder
National Health and Medical Research Council
Funding Amount
$267,645.00
Summary
There is no doubt that mosquito-borne diseases (MBDs) are sensitive to climatic conditions. However, it remains unclear how climate change will influence the distribution and incidence of MBDs. This study aims to use an interdisciplinary and integrated approach to project the impact of future climate change on the transmission of Ross River virus disease - the most common and widespread MBD in Australia, and to provide scientific evidence for developing pulbic health adaptation policies.
The Impact Of Outdoor Aeroallergen Exposure On Asthma Exacerbations In Children And Adolescents
Funder
National Health and Medical Research Council
Funding Amount
$473,924.00
Summary
Asthma is a chronic condition usually diagnosed in childhood and an important public health concern. We do not fully understand what triggers an asthma attack, although outdoor pollen and moulds may be important. This project will establish the relative importance of pollen and moulds in triggering asthma attacks among Australian children. It will fill gaps in our knowledge of environmental triggers of asthma. Such knowledge will improve asthma management and ultimately public health.
Early Life Arsenic Exposure Alters Lung Development And Inflammatory Responses To Virus And Cigarette Smoke
Funder
National Health and Medical Research Council
Funding Amount
$455,380.00
Summary
The contamination of drinking water sources with arsenic is a global health issue affecting millions. While arsenic is a well known cancer causing agent, recent evidence suggests that early life arsenic exposure via drinking water increases the risk of obstructive lung disease in later life. This project aims to examine how the timing and dose of arsenic exposure influences lung development and the response to respiratory insults including viral infection and cigarette smoke.
Deciphering Posttranslational Codes Of The Dioxin Receptor
Funder
National Health and Medical Research Council
Funding Amount
$540,083.00
Summary
The dioxin receptor (DR) is a protein which protects human cells by binding xenobiotics, ie foreign or anti-nutritional chemicals found in food sources and the general environment. When these chemicals bind the DR, it becomes an active gene regulatory protein, turning on genes that are involved in breakdown and excretion of the xenobiotics. Recently it has been found that the DR performs other important functions which are unrelated to xenobiotic breakdown. These include blood vessel development ....The dioxin receptor (DR) is a protein which protects human cells by binding xenobiotics, ie foreign or anti-nutritional chemicals found in food sources and the general environment. When these chemicals bind the DR, it becomes an active gene regulatory protein, turning on genes that are involved in breakdown and excretion of the xenobiotics. Recently it has been found that the DR performs other important functions which are unrelated to xenobiotic breakdown. These include blood vessel development in the embryonic liver and hormone production during the estrous cycle. These observations imply that natural physiological mechanisms also exist for activating the DR, providing it with a separate code to perform these innate functions. A number of man-made chemicals, such as dioxins and PCBs, are especially good at activating the DR. However, they have chlorinated chemical structures, which are not broken down by the protective system. This creates a wide range of severe toxic responses. It has been established that toxicities result from persistent hyperactivation of the DR, but how this hyperactivation induces the toxic outcomes is not known. As the DR has roles in early development and estrogen production, this project will investigate how the DR becomes activated to perform these functions. Our initial experiments have shown that the DR can be activated by normal cell signalling systems, which induce distinct modifications (a distinct code) to the protein. We are comparing this code of modifications to those induced by xenobiotics which are able to be broken down, and dioxins which are resistant to breakdown. We hypothesise that dioxins will give an excessive code of activating modifications, resulting in uncontrolled regulation of genes used in both the developmental and xenobiotic breakdown pathways. We will explore the hypothesis that this gross loss of gene regulatory control underpins the multifarious toxicities of dioxin poisoning.Read moreRead less
Comorbid Affective Disturbance In A Model Of Absence Epilepsy - Shared Causation Linked To Morphological Abnormality?
Funder
National Health and Medical Research Council
Funding Amount
$502,650.00
Summary
People with epilepsy commonly suffer from severe mood disorders, such as depression and anxiety. These disturbances are underdiagnosed and undertreated, and are often more debilitating than the epilepsy. This project will investigate whether treatment of psychiatric disturbance with antidepressants also results in reduced seizure incidence in an animal model of epilepsy. Results generated from the study will provide clinicians strong rationale for aggressive treatment of such mood complaints.