Genetic Dissection Of A QTL Influencing The Development Of Type 2 Diabetes And The Metabolic Syndrome.
Funder
National Health and Medical Research Council
Funding Amount
$129,875.00
Summary
Diabetes is usually associated with obesity and is often part of a wider disturbance affecting an individuals metabolism. These other factors include high blood pressure and the control of fats (eg cholesterol), and sugars (glucose) in the blood stream. Physicians have noted that these abnormalities often cluster together in individuals and have called it the metabolic syndrome, the main long term implication of which is to increase a persons risk of developing heart disease and disorders in blo ....Diabetes is usually associated with obesity and is often part of a wider disturbance affecting an individuals metabolism. These other factors include high blood pressure and the control of fats (eg cholesterol), and sugars (glucose) in the blood stream. Physicians have noted that these abnormalities often cluster together in individuals and have called it the metabolic syndrome, the main long term implication of which is to increase a persons risk of developing heart disease and disorders in blood circulation. The number of affected people with one the major components of the metabolic syndrome, 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 appear 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 3 is likely to carry one or more of these disease genes. But there are over 100 genes in the region, so to help choose the most likely candidates first for testing, we have developed an automated computer database searching program that narrowed the list to the six most likely genes. This project will determine which if any of these genes are involved. 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
Improving Oral health is a priority of the NHMRC Strategic Plan 2003-06. The proposed research is consistent with this priority as we will achieve a better understanding of the cortical control of human jaw muscles, which serves as the foundation for understanding conditions in which their function is impaired, and the development of rational therapies for these conditions. Transcranial magnetic stimulation will be used to activate the motor cortex and corticobulbar descending pathway to the jaw ....Improving Oral health is a priority of the NHMRC Strategic Plan 2003-06. The proposed research is consistent with this priority as we will achieve a better understanding of the cortical control of human jaw muscles, which serves as the foundation for understanding conditions in which their function is impaired, and the development of rational therapies for these conditions. Transcranial magnetic stimulation will be used to activate the motor cortex and corticobulbar descending pathway to the jaw muscles. The AIM 1 study will provide important new information about the functional organisation of the motor cortex in the control of jaw muscles during speech. This information is needed to improve understanding of dysarthria, a common disturbance of speech due to impaired muscular control following unilateral cortical stroke, and less common conditions involving speech motor control such as spasmodic dysphonia (a cranial dystonia) and dysprosody (disturbance of speech articulation and rhythm found in Parkinson s disease). The AIM 2 and 3 studies will provide a comprehensive characterization of cortical inhibitory mechanisms that are an important but poorly understood component of the cortical control of jaw muscles. This information is necessary to understand normal function, and the mechanisms of disturbances to jaw muscle function with neurological disease or injury. The AIM 4 studies will show whether impaired cortical inhibition contributes to the pathophysiology of two poorly understood disorders affecting jaw muscles (bruxism and oromandibular dystonia). Current therapies for these conditions are unsatisfactory, due to a limited understanding of the mechanisms involved. If cortical inhibition is abnormal in these conditions this will lead to novel treatment therapies (e.g., drugs to correct the imbalance, or strategies to induce plastic change in the cortex).Read moreRead less
Liver Cell Transplantation For The Treatment Of Liver Based Metabolic Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$444,143.00
Summary
We propose to investigate the role of liver cell transplantation (LCT) for the therapy of inherited liver-based metabolic diseases using a methylmalonic aciduria (MMA) mouse model. LCT provides an exciting alternative to whole organ transplantation. Initially it was considered liver cells would be immunopriviledged. This has not proven to be the case. Immune modulation will be important. We will also examine immune modulation using antibodies to optimise longterm survival of allogeneic cells.
Are Large Joint Osteoarthritis And Low Back Pain Metabolic Disorders?
Funder
National Health and Medical Research Council
Funding Amount
$381,972.00
Summary
While osteoarthritis (OA) is considered a “wear and tear” disease, there is evidence that OA may be related to a cluster of metabolic abnormalities including obesity, diabetes mellitus, hypertension and high cholesterol. Similarly, low back pain main be linked to a sedentary lifestyle and metabolic changes. This project will examine the relationship between metabolic derangements and back pain and large joint OA in an attempt to better understand these diseases and develop effective treatments.
The Role Of Metabolic And Inflammatory Factors In Cognitive Decline And Cerebrovascular Pathology In The Elderly
Funder
National Health and Medical Research Council
Funding Amount
$945,987.00
Summary
Metabolic factors and measures of inflammation in the body have recently been shown to influence mental function and increase the risk of developing age-related disorders such as Alzheimer’s disease. The influence metabolic factors and inflammation have on function of the ageing brain is likely to be determined by complex interplay between many factors, such as physical health, lifestyle, nutrition and our genes. By studying these factors and how they relate to one another in large groups of eld ....Metabolic factors and measures of inflammation in the body have recently been shown to influence mental function and increase the risk of developing age-related disorders such as Alzheimer’s disease. The influence metabolic factors and inflammation have on function of the ageing brain is likely to be determined by complex interplay between many factors, such as physical health, lifestyle, nutrition and our genes. By studying these factors and how they relate to one another in large groups of elderly individuals, we will be able to determine the role these factors play in brain ageing. In addition we will be able to determine an ‘at risk’ profile for elderly individuals for accelerated ageing effects. Identification of this profile is important as it will allow the development of interventions which may prevent or delay the onset of cognitive decline in late life. We plan to study the impact of metabolic and inflammatory factors on brain ageing and in two groups of elderly individuals both of which are currently being studied in detail by our research team. By using these existing groups we will minimize the costs associated with our research, but maximize the research benefit and the benefit to society. Our groups include a large community sample of elderly individuals aged 70-90 years and a large group of elderly twins aged over 65 years. Our use of twins for the study is particularly important as it will help us separate genetic and environmental influences on the measures. We will measure multiple metabolic and inflammatory factors in the body and determine their relationship to detailed tests of cognitive function and to cerebrovascular pathology on brain magnetic resonance imaging. We will look at how these factors relate to one another and which factors are most strongly associated with accelerated ageing. We will be able to follow subjects in each group over a 2 year interval to see which factors most strongly predict change in cognitive function and cerebrovascular pathology over time. Our research is unique in its inclusion of multiple factors which may affect brain ageing, its ability to look in detail at the contribution of genetic influences on metabolic and inflammatory factors, and in our planned follow-up of these individuals.Read moreRead less
Short Term Effects Of Overfeeding On Metabolic Risk In Humans
Funder
National Health and Medical Research Council
Funding Amount
$380,558.00
Summary
Obesity is associated with increased risk of diabetes, heart disease and cancer. Obesity prevalence is rapidly increasing and consitutes one of the greatest threats to human health. The aim of this study is to determine mechanism-s underlying the close relationship between obesity and insulin resistance by inducing experimental weight gain in humans with and without a genetic predisposition to diabetes. This project will help identify new candidates for anti-diabetes drugs.
Probing The Gene-Environment Interaction In Metabolic Disease
Funder
National Health and Medical Research Council
Funding Amount
$863,910.00
Summary
A major problem with modern medicine is it is based on the law of averages, assuming everybody responds in the same way to a drug or a diet. In view of the diversity between humans as a function of genetic, epigenetic and other factors this is not the case. In the clinic there is marked variation in the response to drugs commonly used to treat patients with type 2 diabetes. This proposal seeks to embrace this complexity to develop a precision medicine approach to future medical care.
Molecular Characterisation Of Adiponectin Receptors: Implications For Adiponectin Action And Resistance
Funder
National Health and Medical Research Council
Funding Amount
$95,137.00
Summary
Adiponectin is a hormone secreted by fat cells with anti-inflammatory, anti-atherogenic and insulin sensitising properties. Adiponectin levels and actions are compromised in obesity and type 2 diabetes. Adponectin mediates its effects via two receptors but the mechanisms are poorly understood. This proposal aims to define the underlying mechanisms with the ultimate goal of identifying novel therapeutic strategies to improve adiponectin's actions.
Determinants And Impact Of Patient-Centred Health Outcomes In Psoriatic Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$84,069.00
Summary
Psoriatic arthritis is a chronic joint disease which is linked with the skin condition called psoriasis. People who have psoriatic arthritis can develop deformities in their joints and suffer from decreased quality of life. Psoriatic arthritis can present in a wide range of ways, but the reasons for this are not understood. This research aims to explain some of this variation and to predict which patients will develop more severe disease so treatment can be targeted to improve their outcome.