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
Glucocorticoid-progesterone Interactions In The Control Of Fetal And Placental Growth
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
The growth and function of the placenta is of critical importance to the successful maintenance and completion of human pregnancy. The placenta is effectively the lifeline of the growing fetus through its supply of nutrients, removal of wastes, and coordination of homone signals that regulate fetal growth and development. If the placenta does not perform these functions adequately, the growth rate of the fetus is compromised and can lead to difficulties before and after birth. This project exami ....The growth and function of the placenta is of critical importance to the successful maintenance and completion of human pregnancy. The placenta is effectively the lifeline of the growing fetus through its supply of nutrients, removal of wastes, and coordination of homone signals that regulate fetal growth and development. If the placenta does not perform these functions adequately, the growth rate of the fetus is compromised and can lead to difficulties before and after birth. This project examines how two important steroid hormones, progesterone and glucocorticoids, interact with growth factors in the placenta to control its growth and function. Progesterone is recognized as 'the hormone of pregnancy' as it helps the mother adapt to pregnancy. Progesterone may also affect the placenta by regulating its synthesis and breakdown of other hormones, and the balance between placental cell proliferation and death. These effects of progesterone will be studied in this project. We will also examine how glucocorticoid hormones regulate the growth and function of the placenta. Glucocorticoids are structurally very similar to progesterone, and are secreted by the adrenal gland in increased quantities during pregnancy. Glucocorticoids exert a wide range of effects on the mother, placenta and fetus; indeed, glucocorticoids are recognized clinically as the single-most importnat signal for fetal maturation in late pregnancy. However, too much glucocorticoid retards fetal and placental growth, and in this project we will study how this occurs in the placenta, and how the placenta may protect itself from detrimental effects of glucocorticoids. We will test whether placental growth is restricted by glucocorticoids through their effects on placental growth factor hormones. Overall, these studies could have important implications for the clinical management of pregnancy, particularly in relation to fetal and placental growth.Read moreRead less
Linking Estrogens, Prostatitis And Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$291,309.00
Summary
Prostatitis is very common and a significant health issue that affects men from their 20's. Estrogens promote inflammation and inflammation is associated with the development of cancer. If this study links estrogens, prostatitis and prostate cancer, we can provide better treatment for prostatitis, thus preventing progression to prostate cancer
Steroid hormones, such as oestrogen and cortisol, act in the body by binding a family of proteins (nuclear receptors) that bind directly to the DNA to regulate genes. The mechanisms underlying this process are complex and involve recruitment of additional molecules or coactivators to improve efficiency. Recently a novel coactivator was identified termed SRA, which remarkably is never made into protein in cells, rather exerting its effects as a RNA. We have identified a novel family of proteins t ....Steroid hormones, such as oestrogen and cortisol, act in the body by binding a family of proteins (nuclear receptors) that bind directly to the DNA to regulate genes. The mechanisms underlying this process are complex and involve recruitment of additional molecules or coactivators to improve efficiency. Recently a novel coactivator was identified termed SRA, which remarkably is never made into protein in cells, rather exerting its effects as a RNA. We have identified a novel family of proteins that bind to SRA in cancer cells, and may well play a critical role in regulating how SRA modulates genes. This project seeks to understand how this family interacts with SRA, the functional effects on breast cancer cells, and the detailed 3-dimensional structure of the family members coupled with SRA. This work will provide novel insight into how SRA regulates steroid hormone action, and may create new potential avenues for developing therapeutics in breast cancer.Read moreRead less
The Role Of Vitamin D In Beta Cell Function, Glucose Tolerance And Diabetes Mellitus.
Funder
National Health and Medical Research Council
Funding Amount
$102,820.00
Summary
A significant proportion of Australians are deficient in Vitamin D, a vitamin obtained from sunlight exposure and to a lesser extent from food. Vitamin D deficiency has been associated with increased risk of Type 2 diabetes. This study aims to demonstrate the mechanisms through which vitamin D affects the insulin-producing cells of the pancreas and to determine whether deficiency affects the body's handling of glucose and subsequent risk of Type 2 diabetes and diabetes in pregnancy.
Understanding The Cause And Consequence Of Impaired Insulin Secretion In The NZO Mouse A Model Of Diabetes.
Funder
National Health and Medical Research Council
Funding Amount
$711,224.00
Summary
Type 2 diabetes is a major health problem affeting over 1 million Australians. A key feature of this disease is reduced secretion of the pancreratic hormone insulin which results in high blood sugar levels. We are using a naturally occurring animal model of diates called the NZO mouse to understand why the pancreas secretes less insulin and the consequences of this defect. This project has the potential of providing better therapeutic strategies for patients with Type 2 diabetes.
Expansion, Differentiation And Functional Analysis Of In Vitro Derived Pdx1+ Pancreatic Progenitors
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Type 1 diabetes is a condition that arises when the body's immune system destroys insulin-producing beta cells within the pancreas. Recent studies have shown that normal glucose control can be restored by replacing the missing beta cells by transplantation of cells from deceased donors. However, the demand for transplant material outweighs supply. The work described in this application seeks to define how insulin-producing beta cells can be derived in the laboratory from embryonic stem cells .
Investigations Of Beta Cell Dysfunction And Death In Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$314,433.00
Summary
Diabetes is a disease that affects 100 million people worldwide and this number is expected to double in the next twenty years. This disease is characterised by high blood sugar levels which over prolonged periods of time can affect the function of the kidneys and eyes as well as causing heart attacks and strokes. A main contributing factor to diabetes is the inability of the pancreas to secrete insulin, the hormone that is responsible for keeping blood sugar levels in the normal range. The reas ....Diabetes is a disease that affects 100 million people worldwide and this number is expected to double in the next twenty years. This disease is characterised by high blood sugar levels which over prolonged periods of time can affect the function of the kidneys and eyes as well as causing heart attacks and strokes. A main contributing factor to diabetes is the inability of the pancreas to secrete insulin, the hormone that is responsible for keeping blood sugar levels in the normal range. The reason for this inability of the pancreas to secrete enough insulin is not known. It is known however, that both genetic and environmetal factors are responsible. The aim of this investigation is to determine the biochemical and genetic reason for decreased insulin secretion from an animal model of diabetes called DBA-2J mouse. Specifically we will be studying the effects of long-term increased sugar and fat on the function of the insulin producing cells of the pancreas, in order to identify the biochemical pathway responsible for reduced insulin secretion. In parallel we will be investigating the gene or genes in DBA-2J mice that are responsible for decreased insulin secretion and pancreatic cell death. This will provide clues as to the genes that may be responsible for diabetes in humans. This project will provide crucial information on the cause of reduced insulin secretion both at the cellular and genetic level, and will lead to a better understanding of the cause of diabetes.Read moreRead less
The Role Fructose-1,6-bisphosphatase On The Regulation Of Hepatic Gluconeogenesis
Funder
National Health and Medical Research Council
Funding Amount
$212,485.00
Summary
Type 2 or adult onset diabetes is a disease characterised by high blood sugar that causes damage to the kidneys, eyes and to the circulation and many patients die from heart attack or stroke. There is an increase in the prevalence of diabetes in Australia and a substantial portion of the health budget is utilised by caring for people with diabetes. Determining what exactly causes the increase in blood sugar levels is critical in the treatment of the disease. It is known that the sugar produced a ....Type 2 or adult onset diabetes is a disease characterised by high blood sugar that causes damage to the kidneys, eyes and to the circulation and many patients die from heart attack or stroke. There is an increase in the prevalence of diabetes in Australia and a substantial portion of the health budget is utilised by caring for people with diabetes. Determining what exactly causes the increase in blood sugar levels is critical in the treatment of the disease. It is known that the sugar produced and released by the liver is an important contributor to the high blood sugar levels found in patients with diabetes. The main biochemical pathway responsible for this is called gluconeogenesis, a complex arrangement of enzymes, which convert amino acids and fat into sugar. Although it is known that this pathway is overactive in patients with diabetes, the exact reason for this is not clearly understood. The aim of this proposal is to produce a transgenic mouse that has an increase in liver sugar production as a result of an increase in gluconeogenesis, and to study its effects on blood sugar levels. Furthermore, studies will be performed to understand the regulation of this pathway by infusing the transgenic mice with insulin, the hormone that inhibits gluconeogenesis. The mechanism of action of insulin will be determined by the measurement of key enzymes that regulate gluconeogenesis. The significance of this grant is to identify possible sites for the development of new drugs or gene therapy that will lead to a decrease in the production of sugar by the liver. This will lead to better control of blood sugar levels and slow down or even prevent the onset of diabetes complications.Read moreRead less