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
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.
Biological, Phenotypic And Public Health Costs Of Risk And Protective Pathways To Non-communicable Disease In Children And Adults: The National Longitudinal Study Of Australian Children
Funder
National Health and Medical Research Council
Funding Amount
$1,521,590.00
Summary
Although a late event for most Australians, chronic diseases present a crippling burden for Australia. This project explores their early roots, before overt disease emerges, in 3500 parents and their children in the Longitudinal Study of Australian Children. We will measure how accumulated stress and buffering characteristics play out in the biology of cell ageing and inflammation, in developing heart, lung, kidney and bone health, and in quality of life and health costs to the population.
Innovative approaches to understanding and limiting the public health risks of Cryptosporidium and Giardia in animals in Australian catchments. Sophisticated molecular typing and modelling will be used to determine if chlorine-resistant parasites in animals in catchments are responsible for infection in humans. Improved catchment management and risk mitigation strategies will be developed during this project, which will make a substantial contribution to the provision of safe drinking water acro ....Innovative approaches to understanding and limiting the public health risks of Cryptosporidium and Giardia in animals in Australian catchments. Sophisticated molecular typing and modelling will be used to determine if chlorine-resistant parasites in animals in catchments are responsible for infection in humans. Improved catchment management and risk mitigation strategies will be developed during this project, which will make a substantial contribution to the provision of safe drinking water across Australia.Read moreRead less
Behavioural, Virological And Immunological Factors Influencing Hepatitis C Virus Infection In Injecting Drug Users
Funder
National Health and Medical Research Council
Funding Amount
$963,437.00
Summary
The hepatitis C virus (HCV) is a major public health problem affecting over 170 million people worldwide. In Australia an estimated 157,000 people have HCV and are at risk of serious disease, and 16,000 new infections occur each year. Treating HCV-related disease is expensive, and this healthcare burden is projected to grow significantly in coming years. Almost all new HCV infections in Australia occur among injecting drug users (IDUs), and despite our world-leading prevention programs, the viru ....The hepatitis C virus (HCV) is a major public health problem affecting over 170 million people worldwide. In Australia an estimated 157,000 people have HCV and are at risk of serious disease, and 16,000 new infections occur each year. Treating HCV-related disease is expensive, and this healthcare burden is projected to grow significantly in coming years. Almost all new HCV infections in Australia occur among injecting drug users (IDUs), and despite our world-leading prevention programs, the virus is spreading. Consensus is emerging that the best hope for control of HCV and related disease lies in a vaccine; our research will lay much of the groundwork for its development. The applicants' research to date shows that IDUs are being infected with HCV more frequently than previously assumed, that many carry multiple strains, and that dominant strains vary rapidly in individuals over time. These results reinforce the view that our prevention methods will not reduce infection rates and that current anti-viral treatments are not the solution. Nevertheless, we also found that some IDUs remain free of HCV infection despite risky behaviour with infected associates; intensive study of the immune functioning of these persistently non-infected individuals holds promise for vaccine development. In our proposed research, a collaboration of leading Australian epidemiologists, virologists and immunologists, we will recruit 210 young IDUs and follow them regularly for two years. Recruits will describe their social networks and nominate IDUs with whom they inject, provide blood samples and be interviewed about their behaviour at 3-month intervals. Individuals with recent and resolved HCV infection, change of dominant strain and lack of infection despite risky behaviour will be identified and their blood analysed for genetic factors that may be linked to immune protection. The outcomes will be crucial to the development and trialling of a vaccine against HCV.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100635
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Demographic distribution models for ecology, conservation & public health. This project aims to advance distribution modelling by developing a new demographic species distribution modelling (DSDM) framework that unites correlative and process-based approaches. This project will develop ecologically realistic models of the distributions of species and diseases, leading to better decision-making in conservation and public health. This will provide significant benefits, such as a better understandi ....Demographic distribution models for ecology, conservation & public health. This project aims to advance distribution modelling by developing a new demographic species distribution modelling (DSDM) framework that unites correlative and process-based approaches. This project will develop ecologically realistic models of the distributions of species and diseases, leading to better decision-making in conservation and public health. This will provide significant benefits, such as a better understanding of where and how to control mosquitoes to reduce malaria transmission in Africa, how best to conserve the vulnerable greater glider in Eastern Australia, and to forecast where and when outbreaks of Ross River virus are likely occur in Victoria.Read moreRead less
Networks, neighbourhoods and newborns: defining household and local area influences on social connectedness, to understand pathways to health. Being socially connected is good for your health, but why? This project will compare social connections in Boroondara and Hume, to explore the influence of neighbourhoods on networks. With this information the project will consider potential pathways to better health outcomes, needed by agencies working to promote neighbourhood connectedness and health.
New methods for integrating population structure and stochasticity into models of disease dynamics. Epidemics, such as the 2007 equine 'flu outbreak and 2009 swine 'flu pandemic, highlight the need to make informed decisive responses. This project will develop new methods that incorporate two important aspects of disease dynamics---host structure and chance---into mathematical models, and determine their impact in terms of controlling infections.
Early Life Stress, Adolescent Brain Development And Risk For Adverse Cognitive And Psychosocial Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$640,595.00
Summary
This project aims to study pre and postnatal childhood factors and examine their association with HPA-functioning, cognition, and mental health during adolescence in the Western Australian Pregnancy Cohort Study (Raine Study). Childhood exposures include not only trajectories of stressful life events, family functioning and mental health status during childhood, but also effects of intrauterine and postnatal growth patterns, and a comprehensive range of psychosocial, familial and environmental f ....This project aims to study pre and postnatal childhood factors and examine their association with HPA-functioning, cognition, and mental health during adolescence in the Western Australian Pregnancy Cohort Study (Raine Study). Childhood exposures include not only trajectories of stressful life events, family functioning and mental health status during childhood, but also effects of intrauterine and postnatal growth patterns, and a comprehensive range of psychosocial, familial and environmental factors. It is our objective to characterise functional polymorphisms for genes related to stress regulation and examine their interactions with early life exposures and their neurobiological consequences. We will also test 16 year old Raine subjects for cognitive ability, and in some we will image their brain activity while performing these tests. We anticipate to enhance the already comprehensive phenotypic Raine Study data base with neurobiological information for future neuroscience studies as the Raine cohort matures. We hypothesise that increased and sustained trajectories of early life stress, family dysfunction or poor mental health during childhood will increase the risk of Raine Study adolescents experiencing: (i) - increased stress sensitivity with higher baseline cortisol levels during adolescence; (ii) - increased adolescent stress sensitivity, if they are carriers of specific haplotypes of the glucocorticoid and mineralocorticoid receptor genes.;(iii) - depression during adolescence, if they are homozygous or heterozygous for the short allele of the serotonin transporter (5-HTT) gene; (iv) - poorer cognitive performance and increased atypical non-prefrontal cortex (PFC) brain activity during cognitive testing as measured by fMRI; and (v) -more mental health problems during adolescence.Read moreRead less