Expanding Diagnostic Approaches For Lynch Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$1,269,355.00
Summary
Currently, there are ~1,000 families who have attended Family Cancer Clinics across Australia who have the hallmarks of having Lynch syndrome, a hereditary bowel cancer syndrome, but who have no gene defect identified, i.e. their cancer is unexplained. Clinicians are challenged by these “Lynch-like” patients as their family cancer risk is unknown. Our research has identified new gene defects in Lynch-like patients. Our aim is to optimise clinical testing approaches for Lynch-like patients.
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
Genomic Profiling For The Prevention Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$425,048.00
Summary
Bowel cancer is a major health issue but is also a preventable disease. Identifying who has a high risk of developing bowel cancer from someone who has a low risk is an important way to ensure preventative medical treatment is targeted to those who are at the highest risk and will ultimately save lives. I will utilise different genomic profiling approaches to identify risk factors for bowel cancer so that they can be used to identify high risk people in the population.
Muir Torre Syndrome: The Role Of IHC And Genotyping In Sebaceous Neoplasia To Facilitate Prevention Strategies In Colorectal And Endometrial Cancer
Funder
National Health and Medical Research Council
Funding Amount
$396,786.00
Summary
Sebaceous neoplasia (SN), may be an early warning sign for Lynch syndrome (LS), an inherited cancer predisposition caused by mutations in a group of genes. There are high lifetime risks of bowel and uterine cancer, for which there are effective risk management plans if the risk is known. Clinicians are challenged by the role of SN in identifying LS. At present, it is hard to differentiate. We aim to determine features to improve the diagnosis of LS carriers.
Oxidative Phosphorylation Regulation And Neuroprotection In Optic Neuropathies
Funder
National Health and Medical Research Council
Funding Amount
$430,231.00
Summary
We have shown clear differences in the mitochodria, cellular organelles that generate energy, between optic atrophy patients who have good vision and those of patients who have poor vision. We believe that these changes represent a compensation mechanisms that preserves mitochondrial energy production and protects optic nerve cells. This study will characterize these differences further with the aim of identfying new treatments for preventing nerve loss and preserving vision.
Assessing a model of the physiological changes at arousal from sleep. Arousals from sleep are common in the elderly and have adverse consequences. This project will investigate a model of the changes in bodily processes (muscle, brain and cardiovascular activation) that occur when humans awaken from sleep.
Increasing the utility of tetanus toxins by protein engineering. There are a variety of common diseases that are the result of muscular defects. Some of these may be able to be treated with an agent that increases muscle tone, thereby giving benefit to the patient in the alleviation of symptoms. This project aims to use some of the most potent substances known, bacterial toxins, and engineer them to be valuable agents for treatment of certain muscular disorders.
The biology, structure and function of bacterial virulence effectors. This project is closely aligned with the National Research Priority of Promoting and Maintaining Good Health and will establish a research framework to investigate novel virulence processes that allow bacterial pathogens to infect humans and cause disease. This fresh approach to the study of bacterial pathogenesis will sit outside classic genetic methods to investigate infection and immunity which rely heavily on genetic manip ....The biology, structure and function of bacterial virulence effectors. This project is closely aligned with the National Research Priority of Promoting and Maintaining Good Health and will establish a research framework to investigate novel virulence processes that allow bacterial pathogens to infect humans and cause disease. This fresh approach to the study of bacterial pathogenesis will sit outside classic genetic methods to investigate infection and immunity which rely heavily on genetic manipulation of the pathogen. Other than providing fundamental information on host-pathogen interactions, this work may lead to novel disease interventions by inhibition of bacterial virulence factor activity and/or enhancement of host inflammatory and immune responses.Read moreRead less
Understanding the biology of reactive oxygen species. This project will utilise forefront technologies to identify and characterise fundamental biological processes involving toxic free radicals that cause infectious disease and cancer. The approach synergises with researchers across disciplines and universities to ultimately identify future drugs to improve and maintain health.
The Role Of IL-18 In Proliferative And Crescentic Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$56,177.00
Summary
Inflammation of the small filters with the kidneys, known as glomerulonephritis, is the commonest cause of kidney failure in Australia. People whose kidneys have failed need either kidney dialysis or a kidney transplant. Our understanding of the immune events that cause glomerulonephritis is patchy. However, it is known that T cells are the directors of immune responses in the body and direct the immune response in glomerulonephritis. Chemical messengers known as cytokines direct the way T cells ....Inflammation of the small filters with the kidneys, known as glomerulonephritis, is the commonest cause of kidney failure in Australia. People whose kidneys have failed need either kidney dialysis or a kidney transplant. Our understanding of the immune events that cause glomerulonephritis is patchy. However, it is known that T cells are the directors of immune responses in the body and direct the immune response in glomerulonephritis. Chemical messengers known as cytokines direct the way T cells behave. One of these cytokines, known as interleukin-18, has been shown to stimulate T cells and other immune cells to induce inflammation that is helpful when the body is fighting infection but is harmful in immune diseases. This project will determine the role of interleukin-18 in glomerulonephritis by studying the way it talks to T cells and the mechanisms by which it incites inflammation in the kidney. Mice with glomerulonephritis will be treated by blocking the actions of interleukin-18 to discover whether interleukin-18 produced by the animal is important in kidney damage induced by glomerulonephritis, to understand the way in which this cytokine works and to assess whether blocking interleukin-18 could be a useful treatment for glomerulonephritis in humans. Current treatments for glomerulonephritis are often ineffective and have unwanted side effects. Knowledge of the way interleukin-18 participates in the immune response in glomerulonephritis may lead directly or indirectly to more effective and more targeted treatments for different forms of glomerulonephritis.Read moreRead less