Physiological Function Of The Novel Vitamin D Receptor Isoform
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
Vitamin D regulates a wide range of physiological systems including those involved in control of calcium blood level and bone health as well as regulation of the immune system and of cell growth. Vitamin D action is mediated through the vitamin D receptor (VDR), a member of a large family of proteins that regulate the activity of specific target genes that control numerous biological functions. A novel, larger form of the human VDR has recently been described in our laboratory. This novel form s ....Vitamin D regulates a wide range of physiological systems including those involved in control of calcium blood level and bone health as well as regulation of the immune system and of cell growth. Vitamin D action is mediated through the vitamin D receptor (VDR), a member of a large family of proteins that regulate the activity of specific target genes that control numerous biological functions. A novel, larger form of the human VDR has recently been described in our laboratory. This novel form shows differences in activity from the shorter VDR form (VDRA) and also has an unusual distribution within the nucleus of the cell that may relate to its function. The present project focuses on further analysis of the relevance of this novel VDR isoform to normal physiology. We hypothesise that the larger VDR isoform has unique characteristics that may modify how vitamin D works in different cells and tissues, on specific target genes and in response to different active forms of vitamin D. These differences depend on this novel isoform s interaction with specific nuclear proteins that regulate the actions of other hormone receptors. The specific aims of this project are to study the functions of the novel VDR isoform in comparison to VDRA: * On different target genes that are either activated or inhibited in response to vitamin D, and on different cell lines from tissues where vitamin D has important roles, like intestine, kidney and bone * In their response to natural and synthetic vitamin D compounds, because of their possible therapeutic applications * In their interactions with intranuclear regulatory proteins, to understand the underlying mechanisms The study of these two forms of the VDR will help to clarify their potentially different cellular roles and their contribution to the wide range of physiological processes regulated by the vitamin D endocrine system. This understanding may open new paths for treatments of human bone and calcium-related diseases.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.
Mechanisms Of Photoprotection By Vitamin D And Analogs
Funder
National Health and Medical Research Council
Funding Amount
$438,186.00
Summary
Our discoveries have clearly shown that vitamin D compounds produced in skin due to UV exposure, have a role in protecting skin from further UV damage. The studies are designed to further examine the mechanism of this photoprotective effect, as it appears to be novel. This will aid in the developmentof agents, which could be used as an after-sun lotion to gain some protection. As Australia has the highest skin cancer rates in the world, this would be of significant health and economic value.
Osteoporosis is a major health burden resulting from bone fractures in older men and women due to progressive loss of bone and weakening of the skeleton. Although there are currently therapies to reduce bone loss, no current treatment effectively reconstructs lost bone. In this project, which is designed to identify new genes that may in the future be targeted by drugs to reverse osteoporosis, we have identified specific sets of genes that appear to work together to increase bone formation. This ....Osteoporosis is a major health burden resulting from bone fractures in older men and women due to progressive loss of bone and weakening of the skeleton. Although there are currently therapies to reduce bone loss, no current treatment effectively reconstructs lost bone. In this project, which is designed to identify new genes that may in the future be targeted by drugs to reverse osteoporosis, we have identified specific sets of genes that appear to work together to increase bone formation. This proposal is aimed at characterising these genes and the ways in which they work to determine whether they may be good targets for new osteoporosis treatments. We will examine the patterns of these genes in bone. We will also use cell cultures in which bone forming cells develop and function, to determine when the genes are expressed and how they function. We will test the ability of the candidate genes to cause an increase in the amount of bone forming activity in these cell cultures. An increase in bone formation may be caused by an increase in the number bone-forming cells, an increase in the activity of the cells, a decrease in cell death, or a combination of these changes. Each possibility will be tested. This research is important because of the need for new osteoporosis therapies to repair weakened bones. The knowledge resulting from this proposal has the potential to provide an important contribution to skeletal health and thus aged health worldwide.Read moreRead less