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
The Effect Of Human ApoE Isoforms And ApoE Receptors On The Clearance Of Oligomeric A 42 By Hepatocytes In Vitro
Funder
National Health and Medical Research Council
Funding Amount
$424,801.00
Summary
Alzheimer's disease (AD) is a progressive memory disorder. Increased production of a short peptide called amyloid- (A ) aggregates to form the sticky masses in the brains of AD patients. The amount of A in the brain is a balance between production and clearance. Surprisingly, we recently demonstrated that the liver clears the majority of A . These results connect AD and cardiovascular disease (CVD), enabling current CVD therapeutics to target A clearance by the liver.
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.
A Multi-setting Intervention To Reduce Sedentary Behaviour, Promote Physical Activity And Improve Childrens Health
Funder
National Health and Medical Research Council
Funding Amount
$860,343.00
Summary
Sedentary behaviours and physical inactivity play a major role in the rising prevalence of obesity among children in Australia. This intervention study will take place in the school and family settings which play a critical role in shaping children's health behaviours. The objective is to determine whether a 2-year behavioural intervention reduces sedentary behaviour and promotes physical activity and results in improved health among 8-9 year old children.
Transcriptional Control Of Blood Vessel Development By Sox18
Funder
National Health and Medical Research Council
Funding Amount
$468,564.00
Summary
Blood vessels play an essential role in maintaining the supply of nutrients to every organ and tissue in the body. Improper development of blood vessels in the embryo can compromise survival of the embryo, and defects in the ability of blood vessels to grow, regenerate and adapt to change during adult life can be life-threatening. The growth of new blood vessels (angiogenesis) is also an important factor in the ability of solid tumours to grow during the progression of cancer. It is therefore of ....Blood vessels play an essential role in maintaining the supply of nutrients to every organ and tissue in the body. Improper development of blood vessels in the embryo can compromise survival of the embryo, and defects in the ability of blood vessels to grow, regenerate and adapt to change during adult life can be life-threatening. The growth of new blood vessels (angiogenesis) is also an important factor in the ability of solid tumours to grow during the progression of cancer. It is therefore of fundamental importance in the health sciences to gain an understanding of how blood vessels form and regenerate. As a result of our collaborative research efforts, we have discovered a gene, Sox18, that appears to regulate blood vessel development by controlling the formation and-or behaviour of endothelial cells, which line the blood vessels and make them impermeable. Our research so far indicates that MICE WITH DEFECTS IN SOX18 DIE FROM VASCULAR DEFECTS, underlining the importance of this gene. THIS PROJECT IS CONCERNED WITH FINDING OUT HOW SOX18 WORKS - exactly what goes wrong in mice lacking this gene, whether Sox18 can influence endothelial cell behaviour in cell culture, how Sox18 comes to be active in endothelial cells, what genes are switched on by Sox18, and what genes Sox18 co-operates with in its role in endothelial cells. The answers to these questions will not only provide fundamental basic information about how blood vessels development is controlled, but also sow the seeds for possible future therapies in which blood vessel development could be stimulated (eg in wound healing) or suppressed (eg in tumour progression) through pharmaceutical intervention.Read moreRead less
Physical, Lifestyle And Psychosocial Determinants Of Spinal Pain Development In Adolescents
Funder
National Health and Medical Research Council
Funding Amount
$682,800.00
Summary
This project aims to understand the development of back and neck pain in adolescence. By the age of 16 around half of all adolescents have suffered back pain and one third have suffered neck pain. For many adolescents this pain is disabling and over a third of sufferers miss school, miss recreation and seek medical help. The current understanding of back and neck pain in adolescence is quite limited - restricting the effectiveness of initiatives to prevent adolescents having to suffer spinal pai ....This project aims to understand the development of back and neck pain in adolescence. By the age of 16 around half of all adolescents have suffered back pain and one third have suffered neck pain. For many adolescents this pain is disabling and over a third of sufferers miss school, miss recreation and seek medical help. The current understanding of back and neck pain in adolescence is quite limited - restricting the effectiveness of initiatives to prevent adolescents having to suffer spinal pain and of treatment of those adolescents unlucky enough to have an episode. Better understanding and interventions for adolescent spinal pain will also have longer term implications by reducing adult spinal pain. Four out of 5 adults will experience spinal pain. In the USA treating adult back pain is the 4th largest health care cost. Many adults with chronic back pain had their first episode during adolescence. A better understanding of spinal pain in adolescence may help prevent it developing into a lifelong disability. We will collect information from 2,000 adolescents on their experience of back and neck pain and on potential physical, lifestyle and psychosocial risk factors. We believe factors such as their posture, muscle capacity, TV and computer use, mental health and social situation all combine to influence whether a person develops back or neck pain. The project is unique as it will not only collect a broad range of information during adolescence, but will also make use of a large database of health, developmental and psychosocial information already collected from these children since birth. With a better understanding of the development of spinal pain we will be able to develop guidelines to help prevent these problems. We will also be able to develop better treatment plans for sub-groups of adolescents with a particular combination of risk factors. Together these initiatives will assist in understanding and breaking the pathway to chronic spinal pain.Read moreRead less
Understanding The Acute And Cumulative Metabolic Effects Of Prolonged Sitting In Adults
Funder
National Health and Medical Research Council
Funding Amount
$416,597.00
Summary
Sedentary behaviour (sitting time) has been linked to an increased risk of chronic illnesses, including type 2 diabetes and obesity, but recent evidence suggests that light-intensity activity (non-exercise activities of daily living) is associated with reduced risk. These studies will examine whether breaking up sitting time with frequent short periods of activity can overcome the negative effects of prolonged sitting on blood glucose and blood fats in overweight older adults.
Erythroid Molecular Cascades Involving The Tyrosine Kinase Lyn
Funder
National Health and Medical Research Council
Funding Amount
$496,500.00
Summary
Mature red and white cells develope from hemopoietic stem cells in the adult bone marrow. The production of red blood cells is primarily controlled by the hormone erythropoietin (Epo). The availability of this hormone in a recombinant form has aided in the treatment of numerous forms of anaemia resulting from kidney failure, malignancies, and AIDS. Previously we had identified that the protein Lyn must be present inside primitive red blood cells for Epo to stimulate them to become mature functio ....Mature red and white cells develope from hemopoietic stem cells in the adult bone marrow. The production of red blood cells is primarily controlled by the hormone erythropoietin (Epo). The availability of this hormone in a recombinant form has aided in the treatment of numerous forms of anaemia resulting from kidney failure, malignancies, and AIDS. Previously we had identified that the protein Lyn must be present inside primitive red blood cells for Epo to stimulate them to become mature functional cells. Recently, we have demonstrated that mice lacking the Lyn gene develope major problems with their red blood cells. We have identified several molecules which interact with Lyn in red blood cells. We have shown that a molecule called Cbp is important for Epo function in individual red blood cells and now we plan to investigate its function in whole animals. We have shown that a new molecule called Arp is important for red blood cell development. This protein moves in and out of the nucleus (where DNA is stored) and may be important in the regulation of genes needed for red blood cells. The third gene (AFAPbeta) is also novel and is closely related to another called AFAP-110, which can exert effects on the structure of a cell. Since red blood cells have to shrink considerably during their development, the role of AFAPbeta on red blood cell structure will also be investigated. From these experiments we should develop a much better understanding of how the production of red blood cells is controlled and how diseases of red blood cells (such as anaemia) occur.Read moreRead less
A Behavioural Intervention For The Adoption & Maintenance Of Physical Activity In Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$334,955.00
Summary
For people with type 2 diabetes (T2DM) it is essential that blood glucose levels are managed well to reduce the risk of developing complications. Physical activity is essential for maintaining glucose levels because it helps make the muscles use glucose more effectively. In particular, being active through strength training not only improves blood glucose levels, but can be very effective for maintaining good physical functioning, which is known to be reduced by having T2DM. This study builds on ....For people with type 2 diabetes (T2DM) it is essential that blood glucose levels are managed well to reduce the risk of developing complications. Physical activity is essential for maintaining glucose levels because it helps make the muscles use glucose more effectively. In particular, being active through strength training not only improves blood glucose levels, but can be very effective for maintaining good physical functioning, which is known to be reduced by having T2DM. This study builds on our earlier research which demonstrated significantly improved blood glucose levels from a strength training program for older adults with T2DM. The strength training program is to be administered nationally in a research to practice trial (Lift for Life); however, the original research found that those who did not complete the program as it was intended (ie, poor adherence) did not show significant improvements in blood glucose levels. Furthermore, maintenance of strength training exercises after completion of the program was poor and resulted in return of blood glucose levels back to pre-starting levels. In people without diabetes, we have collected pilot data that shows that the use of behavioural strategies based on behavioural theories whereby each person's motivations and barriers are taken into consideration is more effective than the traditional one-treatment-fits-all approach. This study will evaluate the effectiveness of using behavioural strategies for improving adherence and maintenance to the Lift for Life strength training program (Enhanced L4L) for older adults with T2DM compared with the Standard L4L program. It will also follow-up participants 6 months later to determine the extent to which the changes in behaviour can be maintained. The study will provide information that will assist in the design, delivery and uptake of programs to improve treatment strategies in older adults with T2DM through the maintenance of healthier behaviours and lifestyles.Read moreRead less