Exploiting Sexual Differences In Germline Biology To Resolve The Causes Of Germline Mutation
Funder
National Health and Medical Research Council
Funding Amount
$315,914.00
Summary
Mutagenesis during the production of sex cells is a fundamental biological process and the cause of inherited human disorders. These disorders span the entire spectrum of diseases that have a genetic component, such as autoimmune diseases and cancers, therefore influencing all age groups. A better understanding of the mechanisms underlying this process is a priority since it is the essential knowledge required for understanding all of the factors that contribute to this array of debilitating dis ....Mutagenesis during the production of sex cells is a fundamental biological process and the cause of inherited human disorders. These disorders span the entire spectrum of diseases that have a genetic component, such as autoimmune diseases and cancers, therefore influencing all age groups. A better understanding of the mechanisms underlying this process is a priority since it is the essential knowledge required for understanding all of the factors that contribute to this array of debilitating diseases, and for devising effective preventative and diagnostic measures. To attain this understanding necessitates establishing the mechanistic origins of germline mutagenesis. Two basic approaches are employed to understand this process. The first assesses the incidence of mutation in pedigrees. This identifies the spectrum of risk mutations underlying the specific disease surveyed. Because other biological processes also influence these observations, the results from this approach do not reflect the underlying germline mutation spectra and are therefore not translatable between diseases. As mutations are rare events, it is prohibitive to obtain sufficient observations to resolve the underlying mechanisms. The second approach employs comparative genomic data, and uses differences in germline biology to estimate sex-biased effects. This comparative approach benefits from the accumulation of mutations over vast periods of time. The approach has not, however, been applied to diagnose the mechanistic origins of mutations. In this project, we will apply the enormous volume of comparative sequencing data to relate components of the mutagenic spectrum with sexual differences in germline biology. The project will differentiate between different types of mutations, and their association with specific processes will be established. The results will be a determination of the relative contributions of different mechanisms of mutation to germline mutagenesis.Read moreRead less
A Worldwide Study Of Cancer Risk For Lynch Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$710,761.00
Summary
People with the genetic Lynch syndrome are more likely to get cancer but we cannot accurately predict who will get cancer and when. Doctors need this information to improve cancer prevention. Large collaborative studies are needed for this research. We have agreement from the 115 researchers to combine, into a single resource, 8,863 family trees of Lynch syndrome. We will analyse this data to determine the risk of cancer and whether it differs by sex, age, or nationality.
Understanding Causes Of The Rising Incidence Of Thyroid Cancer – What Can Mutations In The BRAF Oncogene Tell Us About Causes And Diagnostic Pathways For Thyroid Cancer?
Funder
National Health and Medical Research Council
Funding Amount
$610,222.00
Summary
The occurrence of thyroid cancer has increased rapidly over the last 25 years but the cause is unknown. The increase may reflect ‘over-diagnosis’ of less harmful cancers or greater exposure to causes of this cancer. Evidence suggests that a gene mutation (BRAF) in thyroid cancers is important in understanding the drivers of the increase. This study will examine the increase in thyroid cancer by investigating causes and diagnostic pathways considering the presence or absence of BRAF mutations.
Predicting The Individual Risk Of Prostate Cancer In Australian Men
Funder
National Health and Medical Research Council
Funding Amount
$348,656.00
Summary
Prostate cancer is a major cause of disability and death in Australian men. A number of factors, particularly age and family history, influence the risk of prostate cancer but, in contrast to breast cancer, we don't know what is the risk of developing prostate cancer over a period of time for a man with a specific set of risk factors. In fact, while a number of statistical models have been developed that use a woman's risk factor profile to estimate her risk of breast cancer, none is currently a ....Prostate cancer is a major cause of disability and death in Australian men. A number of factors, particularly age and family history, influence the risk of prostate cancer but, in contrast to breast cancer, we don't know what is the risk of developing prostate cancer over a period of time for a man with a specific set of risk factors. In fact, while a number of statistical models have been developed that use a woman's risk factor profile to estimate her risk of breast cancer, none is currently available for prostate cancer. We will apply standard statistical methods to existing data from the Australian Risk Factors for Prostate Cancer study and from the Australian Institute of Health and Welfare to develop a prostate cancer risk prediction model. We will test how factor like age, detailed family history, diet, baldness status and possibly previous PSA tests and prostate biopsies predict the risk. After developing the model, we will test the accuracy of the predictions in three ways. First, using existing data from the Australian Prostate Cancer Family Study, we will see whether the number of cases in a group of men is close to the number predicted by the model (calibration). Second, to test whether the model discriminate well men who develop prostate cancer from those who do not, we will collect family trees in a sample from the Melbourne Collaborative Cohort Study. We will use these data also to estimate the optimal cut point: men above this level of risk will be considered at high risk. Third, we will apply the model to existing data from the Dutch Prostate Cancer Family Study (DPCFS) to test whether the optimal cut point identify high-risk men and to validate the model in a non-Australian population. Finally, we will prepare a computer package that health professionals will use as decision-making tool in different scenarios including individual cancer risk assessment, design of prevention trials and targeting prevention programs to high-risk men.Read moreRead less
Intelligent Total Body Scanner For Early Detection Of Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$499,963.00
Summary
Melanoma is the 4th most common cancer in Australia; the main screening tool is a time-consuming total body examination with a hand-held dermoscope. This project aims to develop a total body scanner using fast-refocusing lenses to take total body dermoscopy images of all skin lesions in approximately 6 minutes, integrated with a computer aided diagnostic tool providing a risk score for each lesion incorporating medical history, genotypic and phenotypic risk markers.
I am a scientist aiming to improve health outcomes by facilitating the collection and unification of data on human genetic variation together with its clinical impact on human health.
Estimation Of Transient Increases In Bleeding Risk Associated With Physical Activity In Children With Haemophilia
Funder
National Health and Medical Research Council
Funding Amount
$102,143.00
Summary
Haemophilia A and B are genetic conditions which affect 1 in 7,000 males in Australia. These disorders cause frequent bleeding due to problems with the clotting factor in blood. Over the past decade there has been a move to administer clotting factor to children with haemophilia in order to prevent bleeds and the consequent damage to joints that occurs when bleeds occur in a joint. Participation in vigorous physical activity and sport is thought to increase the risk of bleeding. Because of this, ....Haemophilia A and B are genetic conditions which affect 1 in 7,000 males in Australia. These disorders cause frequent bleeding due to problems with the clotting factor in blood. Over the past decade there has been a move to administer clotting factor to children with haemophilia in order to prevent bleeds and the consequent damage to joints that occurs when bleeds occur in a joint. Participation in vigorous physical activity and sport is thought to increase the risk of bleeding. Because of this, children are often given clotting factor prior to playing sport. However clotting factor is extremely expensive. For example, a boy wanting to play tennis three times a week would require three injections of cIotting factor per week at a cost of approximately $250,000 a year. To date there is no good evidence about which physical activities are likely to increase the risk of bleeding. If this information was available clinicians would be able to optimise timing of administration of clotting factor so that it is administered prior to activities associated with high risk of bleeds. Another reason to quantify risk of bleeds associated with activity is to inform decisions about participation in physical activity. Every boy with haemophilia wants to know if he can play sport or ride a skateboard or jump on a trampoline. Informed decisions about participation require accurate estimates of risk. This study will use an innovative design to provide, for the first time, accurate estimates of the risk of bleeding associated with physical activity. This information will form the basis for clinical practice guidelines regarding participation in physical activity.Read moreRead less
Oxidation Of Mismatch: A New Concept For Mutation Detection Which Avoides A Separation Method In Mutation Scanning
Funder
National Health and Medical Research Council
Funding Amount
$143,000.00
Summary
Detection of faults (mutations) in genes is expensive but essential for proper genetic health care. Because of the cost of such tests many people are not diagnosed either through diagnostic labs or research of the cost of such tests many people are not diagnosed either through diagnostic labs or research projects. Such research projects are inhibited due to the complexity of the current methods. Current methods are complex and expensive, especially looking for a possible fault, due to what is ca ....Detection of faults (mutations) in genes is expensive but essential for proper genetic health care. Because of the cost of such tests many people are not diagnosed either through diagnostic labs or research of the cost of such tests many people are not diagnosed either through diagnostic labs or research projects. Such research projects are inhibited due to the complexity of the current methods. Current methods are complex and expensive, especially looking for a possible fault, due to what is called a preparation step on complex and expensive equipment. We will develop and commercialise a simpler test because separation is avoided.Read moreRead less
Reducing Colorectal Cancer Burden In Young Adults: Precision Prevention And Early Detection
Funder
National Health and Medical Research Council
Funding Amount
$1,449,800.00
Summary
Bowel cancer rate in young adults before age 50 is increasing worldwide including Australia. Since it is impossible to screen everyone, it is critical to identify who is likely to develop the disease, to optimise screening. Using the world's largest resource for young-onset bowel cancer, I will conduct studies to generate high-quality evidence to inform how to best prevent bowel cancer in young adults and translate into the policy and practice, to reduce colorectal cancer burden in young adults.
Immunisation Safety And Adverse Events: Improving Our Understanding Of Causes And Management
Funder
National Health and Medical Research Council
Funding Amount
$295,223.00
Summary
As the incidence of vaccine preventable diseases declines, adverse events following vaccination become increasingly important for both public and providers. This fellowship aims to improve our understanding of the risks of vaccination, potential causes, including genetic predisposition and long term clinical outcomes. A range of epidemiological, clinical and genetics studies will be performed. All these studies are targeted to understand who, what, how and why vaccine reactions occur and what ca ....As the incidence of vaccine preventable diseases declines, adverse events following vaccination become increasingly important for both public and providers. This fellowship aims to improve our understanding of the risks of vaccination, potential causes, including genetic predisposition and long term clinical outcomes. A range of epidemiological, clinical and genetics studies will be performed. All these studies are targeted to understand who, what, how and why vaccine reactions occur and what can be done to prevent or manage them better.Read moreRead less