Reversal Of Diabetes In Pigs Using Liver-directed Gene Therapy
Funder
National Health and Medical Research Council
Funding Amount
$573,807.00
Summary
Type I diabetes mellitus is caused by the autoimmune destruction of the beta cells of the pancreas that secrete insulin. We have shown that we can cure diabetes in spontaneously diabetic mice by delivery of the insulin gene to the liver using a non-pathogenic viral delivery system. The study aims to repeat this work in pigs which have similar physiology to humans. If successful this would be proof-of-principle that we could theoretically control blood glucose levels in humans.
Epidermal Growth Control In Psoriasis And Normal Skin
Funder
National Health and Medical Research Council
Funding Amount
$451,980.00
Summary
Our skin protects us from damage, dehydration, infection and harmful UV radiation. At the same time, we expect it to remain healthy, smooth and looking good. How the skin, and more particularly its upper layer, the epidermis, adapts to all these requirements is a complex problem yet to be fully understood. This question forms the basis of our project proposal. The epidermis is a continuously self-renewing tissue, in which cells have an average life of 30 days before they are invisibly shed to th ....Our skin protects us from damage, dehydration, infection and harmful UV radiation. At the same time, we expect it to remain healthy, smooth and looking good. How the skin, and more particularly its upper layer, the epidermis, adapts to all these requirements is a complex problem yet to be fully understood. This question forms the basis of our project proposal. The epidermis is a continuously self-renewing tissue, in which cells have an average life of 30 days before they are invisibly shed to the outside. In normal states and when responding to injury or disease, this cell turnover speed can be finely tuned, for example accelerated in the case of a healing wound. In contrast, if damaged by the sun, epidermal cells undergo a form of cell suicide (apoptosis) to prevent tumours forming from cells with damaged genes. This changing turnover speed is controlled by a series of growth factors, or cytokines. Insulin-like growth factor-I (IGF-I) is a unique cytokine that can control both cell turnover rate, and cell death. We aim to uncover the complex biochemical interactions that allow the epidermal IGF-I system to achieve this seemingly contradictory task. This study is important because when the epidermis loses the ability to finely tune its turnover speed, ulcers, sun damage, the common skin disorder psoriasis, or worse still, skin tumours, arise. This project explores ways of manipulating the IGF-I system to prevent this, and builds on some technology developed by the research group that has already proven effective in the control of psoriasis. The project also promises to discover undiscovered growth regulators that could be used in new gene therapies for skin overgrowth diseases.Read moreRead less
Regulation And Effect Of The Growth Hormone, IGF-I, And IGF-Binding Protein Response To Acute Exercise
Funder
National Health and Medical Research Council
Funding Amount
$367,197.00
Summary
The body's ability to respond to physiological stress is vital to survival. This series of studies aims to examine the hormonal responses to physical exercise. In studies recently completed to determine how to detect Growth Hormone (GH) abuse in the Olympics, we have discovered a new system of hormones that respond to exercise. These Insulin-like Growth Factors (IGF) and their IGF-Binding Proteins (IGF-BP) are normally controlled by GH. The IGF-IGF-BP system normally acts to control of many cell ....The body's ability to respond to physiological stress is vital to survival. This series of studies aims to examine the hormonal responses to physical exercise. In studies recently completed to determine how to detect Growth Hormone (GH) abuse in the Olympics, we have discovered a new system of hormones that respond to exercise. These Insulin-like Growth Factors (IGF) and their IGF-Binding Proteins (IGF-BP) are normally controlled by GH. The IGF-IGF-BP system normally acts to control of many cellular and organ functions in many different tissues of the body. For example they stimulate protein accumulation and muscle growth, and have actions to control blood glucose in conditions like diabetes. Little is known about what regulates the production of the IGF and IGF-BPs in response to physical exercise. We aim to examine whether GH, either as an acute pulse as occurs naturally, or a direct effect of exercise that is not GH-mediated, is responsible for the increase in IGF and IGFBPs. This may uncover a new means of controlling this powerful hormonal system. In addition, we will examine whether GH or IGF-I, alone and together, influence the body's ability to respond to the stress of exercise (e.g., controlling fuel use, cardiovascular and kidney responses). Such information will allow greater understanding of this important hormonal system, so that in novel therapies may be developed for conditions such as normal ageing, the wasting states that accompany severe surgical or infectious stress, or conditions with abnormal blood glucose regulation such as diabetes. In addition, this information will permit greater sophistication in the detection of GH and related compounds in elite athletes. Unfortunately, GH is also being abused by non-elite athletes and high-school children. We believe our efforts will asist in the detection and prevention of these more general societal health issues.Read moreRead less
Mechanisms Of Hypoglycaemic Damage In Developing Brain- A Protective Role For The Insulin-like Growth Factor System
Funder
National Health and Medical Research Council
Funding Amount
$408,055.00
Summary
The developing brain in the newborn infant or young child is vulnerable to many damaging influences. It is highly dependent on its essential fuel, glucose. Hypoglycemia, or lack of glucose availability, is therefore among the most damaging insults to the young brain, potentially leading to learning difficulties, developmental delay, cerebral palsy or epilepsy. Babies born premature or very small are at risk, as are those exposed to excessive insulin, such as infants of diabetic mothers. Children ....The developing brain in the newborn infant or young child is vulnerable to many damaging influences. It is highly dependent on its essential fuel, glucose. Hypoglycemia, or lack of glucose availability, is therefore among the most damaging insults to the young brain, potentially leading to learning difficulties, developmental delay, cerebral palsy or epilepsy. Babies born premature or very small are at risk, as are those exposed to excessive insulin, such as infants of diabetic mothers. Children with diabetes are also at risk, when their therapy with insulin may at times be excessive, leading to hypoglycaemia and impaired glucose availability for the brain. This proposal is examining at the cellular level the mechanisms involved in loss of brain cells in the face of glucose starvation in these various conditions. We are using several in vitro models where we can grow segments of developing mouse brain or human nerve cells in a dish, compared to studies with mice subjected to low blood glucose (hypoglycemia). After establishing that our laboratory models are representative of the whole animal, we will explore the cellular mechanisms involved in neuronal death following hypoglycaemia, particularly the interaction between the insulin-like growth factor (IGF) and other cell survival genes. We will also examine the possibility that treatment with IGF will reduce the loss of nerves in the brain after an episode of hypoglycemia. This may offer new and effective early treatment for this damaging brain injury in both newborn babies and children with insulin-dependent diabetes.Read moreRead less