Identification Of Novel Genes Influencing Development Of Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$558,920.00
Summary
Type 2 diabetes is usually associated with obesity and is often part of a wider disturbance affecting an individual's energy metabolism. The number of affected people with type 2 diabetes has trebled since 1981 in Australia and is still increasing. Apart from individual suffering, this presents a major public health burden for the country (approx $3 billion annually). Currently available lifestyle based and pharmaceutical therapies are inadequate to control the increasing numbers of affected ind ....Type 2 diabetes is usually associated with obesity and is often part of a wider disturbance affecting an individual's energy metabolism. The number of affected people with type 2 diabetes has trebled since 1981 in Australia and is still increasing. Apart from individual suffering, this presents a major public health burden for the country (approx $3 billion annually). Currently available lifestyle based and pharmaceutical therapies are inadequate to control the increasing numbers of affected individuals. Unfortunately the cause of disease is poorly understood, although genetic factors are known to be important, in other words it runs in the family. This project proposes to identify some of these factors (genes) and how they contribute to the disease. Using molecular flags on the DNA (like DNA fingerprinting) we have previously found that a small region on chromosome 12 is likely to carry one or more of these disease genes. But there are over 100 genes in the region. To help choose the most likely candidates first for testing, we have developed an automated computer database searching program ranked the genes based on what is already known about them. We have also taken a large number of physiological measures in a large group of people. Some of these measures are controlled by the same chromosome 12 region - thus to improve our chances of finding the genes quickly we will look at those that change the most between people with diabetes and people without diabetes. In this project we shall investigate the 20 genes most likely affect diabetes based on changes in physiological measures and what is already known about them. A successful finding means we will know more about the mechanism of disease development and be able to better develop new therapies for treatment and prevention. If none of these genes are the culprit, we would continue examination of the next set of genes likely to be involved and so on until we are successful.Read moreRead less
Gestational diabetes is an important medical condition. We plan to investigate two subgroups of women with gestational diabetes. Firstly, women who have diabetes antibodies in pregnancy. Secondly, women who have a mild form of diabetes caused by a single gene mutation, who may be first identified during pregnancy. Correct identification of these subgroups of women is important for immediate and long-term management of both the mother and her fetus.
Development Of A Multi-faceted Diagnostic And Predictive Tool To Characterise Type Of Diabetes, Therapeutic Progression And Outcome
Funder
National Health and Medical Research Council
Funding Amount
$352,550.00
Summary
Diabetes is diagnosed using clinical assessment complemented by a few selected basic conventional laboratory tests. We plan to determine, in a representative community-based sample of Australian with diabetes, whether additional knowledge of genetic markers, diabetes-related antibody levels and tests of insulin secretory capacity adds to diagnosis of diabetes type, prediction of therapeutic progression over time, complications and death.
Biomarkers, Related Mechanisms And Technology To Improve Diabetes Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$474,513.00
Summary
Diabetes can cause eye, kidney, heart and nerve damage. The applicant will lead human studies of treatments to prevent complications, improve blood glucose and co-ordinate care. Early outcome prediction would enable better treatment of high-risk people, monitoring of therapy, and development of new treatments. Dr Jenkins also has a network with data and samples from over 35,000 people with diabetes, preliminary data, and a team to measure markers and test new treatments in the lab.
Kallikrein Gene Variants In Prostate Cancer: Analysis Of Gene Regulation And Diagnostic/Prognostic Use
Funder
National Health and Medical Research Council
Funding Amount
$486,801.00
Summary
Prostate cancer is the most common male cancer in Australia. However, early detection through screening programs has proven challenging, and about 30% of the 10,000 new cases diagnosed annually already have advanced disease. Hence, there is a fundamental need for increased basic research in prostate cancer etiology (cause) and tumour biology, and a critical requirement for methods that will assist in earlier detection of the disease and predict progression. A family of proteins called kallikrein ....Prostate cancer is the most common male cancer in Australia. However, early detection through screening programs has proven challenging, and about 30% of the 10,000 new cases diagnosed annually already have advanced disease. Hence, there is a fundamental need for increased basic research in prostate cancer etiology (cause) and tumour biology, and a critical requirement for methods that will assist in earlier detection of the disease and predict progression. A family of proteins called kallikreins (including prostate specific antigen, PSA) are often associated with clinical features of prostate cancer. We will characterise genetic variants (polymorphisms) in kallikrein genes that are consistently over-produced in prostate cancer, and determine whether they cause more protein to be produced in cells grown in the laboratory and in tumour tissue, and-or give rise to different expression products or splice variants. We will use bioinformatics (computer programs) to characterise published kallikrein gene sequences and to examine them for genetic variants that might be related to changes in gene expression or to splice variants. We will then use a case-control study, involving 1200 men with prostate cancer and 1200 healthy men, to determine whether these gene variants are associated with an increased risk of prostate cancer or with clinical aspects of the disease. Finally, we will examine the functional significance of the gene variants. This project represents an important and novel combination of molecular biology with the study of clinical disease at the population level, in the relatively new field of molecular epidemiology. It will clarify the role of kallikrein gene variants in prostate cancer risk and progression. The technologies may ultimately prove useful clinically for diagnosis of prostate cancer or for monitoring of treatment and prognosis, and hopefully will assist in clinical decision-making.Read moreRead less
Identification And Characterisation Of A Gene Causing Insulin Hypersecretion In A Mouse Model Of Diabetes Susceptibility
Funder
National Health and Medical Research Council
Funding Amount
$430,320.00
Summary
Diabetes is a disorder primarily characterised by the inability to produce and secrete the pancreatic hormone insulin, which regulates plasma sugar levels. This results in increased sugar levels which cause diabetic complications such as retinopathy and nephropathy. The inability to produce and secrete insulin is due to both defects in function as well as a reduction in pancreatic beta cells. Paradoxically it has been shown that some patients who are at risk of develping diabetes actually secret ....Diabetes is a disorder primarily characterised by the inability to produce and secrete the pancreatic hormone insulin, which regulates plasma sugar levels. This results in increased sugar levels which cause diabetic complications such as retinopathy and nephropathy. The inability to produce and secrete insulin is due to both defects in function as well as a reduction in pancreatic beta cells. Paradoxically it has been shown that some patients who are at risk of develping diabetes actually secrete more insulin than normal. Furthermore it has been suggested that this increase in insulin secretion actually may be associated with the decreased production and secretion of insulin characteristic of diabetes. The DBA-2 mouse is a model of reduced insulin production and secretion when exposed to high sugar levels or diabetes. However we have shown that in the normal non-stressed state DBA-2 mice actually secrete more insulin than normal and that this occurs from a very early age, suggesting that this trait is inherited. We have subsequently performed genetic studies and have identified a segment of DNA containing 10 genes associated with increased insulin secretion in DBA-2 mice. The level of one of these genes we have called Hip1 is increased 5-fold in DBA-2 mice, providing a candidate gene for increased insulin secretion in this model of diabetes susceptibility. However, whether Hip1 is also responsible for reduced insulin production and secretion in the DBA-2 mouse is not known. Therefore the overall hypothesis of this project is that the gene Hip1 which is associated with increased insulin secretion is also responsible for reduced insulin production and secretion when DBA-2 mice are exposed to high sugar or obesity. Determining why Hip1 is increased and whether it results in diabetes in DBA-2 mice may provide a reasonable candidate for the development of therapeutic interventions which may prevent the progression of diabetes in some patients.Read moreRead less
Elucidating Genetic Mechanisms Responsible For Familial Hyperaldosteronism Type II
Funder
National Health and Medical Research Council
Funding Amount
$424,812.00
Summary
Primary aldosteronism (PAL) is the commonest specifically treatable and potentially curable form of hypertension (high blood pressure), a common disease, expensive to treat, with serious morbidity and mortality. This project will use cutting edge technology to gain new knowledge concerning how genes regulate the body's production of aldosterone (salt hormone), which will help us understand how PAL develops and how common it is, and could lead to better approaches to diagnosis and treatment.
ARMC5 And Other Genetic Contributions In Endocrine Neoplasia
Funder
National Health and Medical Research Council
Funding Amount
$124,676.00
Summary
The adrenal glands secrete essential hormones and can enlarge or develop tumours leading to conditions including obesity, high blood pressure, diabetes, brittle bones and infections. We recently found that adrenal enlargement and tumours may be due to changes in the ARMC5 gene. We will perform genetic testing in affected patients across Australia to evaluate the roles of ARMC5 & other genes. Our goal is to better understand how these conditions develop so as to improve diagnosis and treatment.
The overall aim is to improve treatments and outcomes for people with osteoporosis. This will be achieved by better predicting those who are likely to fracture and subsequently those who do well post fracture from those who do poorly. Following an osteoporotic fracture there is an increased risk of re- fracture and of premature death. This research will define those risk factors for fracture, re-fracture and early death in a large group of men and women followed for over 20 years.