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
Targeting Nicotinamide Adenine Dinucleotide Biosynthesis To Improve Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$844,596.00
Summary
Nicotinamide adenine dinucleotide (NAD) is a cellular metabolite that regulates many biological processes. NAD levels decline with age and also in obesity and interventions that increase NAD levels produce favourable metabolic effects. In this proposal we will utilise a range of novel experimental models to define the molecular pathways that mediate the beneficial effects of NAD.
Polycystic ovary syndrome (PCOS) affects a striking 9-21% of women of reproductive age. PCOS is an important health problem and can affect menstrual cycles, fertility and increase risk of diabetes and mood disorders. There is a lack of longitudinal studies that women with PCOS over time to examine the key determinants of PCOS, long-term impact of obesity and factors contributing to PCOS complications.
Early Retinal Vessel Changes In Diabetes And The Metabolic Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$212,500.00
Summary
Diabetes mellitus affects a large proportion of adult Australians. Furthermore, many non-diabetic Australians are at high risk of developing diabetes (e.g., people with lesser glucose abnormalities, and those who are obese, have high blood pressure, or have high lipid levels). It has been suggested that diseases affecting small blood vessels (microvascular disease) in the body is closely related to the development of both diabetes and the pre-diabetes state. The current study will examine the re ....Diabetes mellitus affects a large proportion of adult Australians. Furthermore, many non-diabetic Australians are at high risk of developing diabetes (e.g., people with lesser glucose abnormalities, and those who are obese, have high blood pressure, or have high lipid levels). It has been suggested that diseases affecting small blood vessels (microvascular disease) in the body is closely related to the development of both diabetes and the pre-diabetes state. The current study will examine the relationship of microvascular disease in the retina (at the back of the eye) to diabetes, pre-diabetes status and diabetes complications. We will use a computer-imaging technique to measure the diameters of retinal blood vessel from digital photographs taken in 2,177 participants of the 1999-2000 Australian Diabetes, Obesity and Lifestyle (AusDiab) Study, a community-based survey of people aged 25 years and older examining risk factors and complications of diabetes. In the proposed study, we aim to answer the following questions: 1) Are changes in the retinal blood vessel diameter (e.g., narrowed or dilated vessels) associated with diabetes and pre-diabetes? 2) Are these retinal vessel changes related to obesity, high blood pressure and high lipid levels? 3) Are retinal vessel changes related to diabetes complications, such as heart disease, kidney disease, nerve problems and foot ulcers? 4) Do retinal vessel diameter changes predict people who will subsequently develop diabetes, irrespective of their risk factor profile? Using this well-characterized population, and existing digital retinal photographs, the proposed study will offer a unique and cost-effective opportunity to address important gaps in our understanding of how diabetes and pre-diabetes develop, and whether they are related to microvascular diseases. This may ultimately lead to new treatment and preventive approaches targeted at the small blood vessels in the body.Read moreRead less
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
Polycystic Ovary Syndrome - Targeting The Sympathetic Nervous System To Improve Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$353,140.00
Summary
Polycystic ovary syndrome (PCOS) affects approximately 10% of women of reproductive age, rendering it a major public health issue. Due to the combined development of abdominal obesity, hypertension and insulin resistance patients with PCOS are at increased risk of developing heart disease. The etiology of PCOS remains unknown but work by us implicates involvement of the sympathetic nervous system. We aim to elucidate the role of the sympathetic nervous system in PCOS and to examine the effect of ....Polycystic ovary syndrome (PCOS) affects approximately 10% of women of reproductive age, rendering it a major public health issue. Due to the combined development of abdominal obesity, hypertension and insulin resistance patients with PCOS are at increased risk of developing heart disease. The etiology of PCOS remains unknown but work by us implicates involvement of the sympathetic nervous system. We aim to elucidate the role of the sympathetic nervous system in PCOS and to examine the effect of pharmacological treatment targeting this system.Read moreRead less