The Immune And Metabolic Effects Of Vitamin D In Adult-onset Autoimmune Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$50,551.00
Summary
I am conducting a trial of vitamin D in adults with diabetes to determine if it improves the ability of the pancreas to make insulin, improves the efficiency of insulin action and suppresses the immune cells that attack the pancreas. If these effects are seen, it implies that vitamin D may be an important adjunct treatment in the management of diabetes. It may also delay the need for insulin injections in people with type 1 diabetes and it may even have a role in preventing type 1 diabetes.
Coenzyme A Synthesis In The Human Malaria Parasite, Plasmodium Falciparum
Funder
National Health and Medical Research Council
Funding Amount
$428,250.00
Summary
Malaria is responsible for hundreds of millions of cases and an estimated 1.5-2.7 million deaths each year. The disease is caused by a microscopic parasite which is becoming increasingly resistant to antimalarial drugs. There is a very real possibility that there will soon be parts of the world in which malaria is an untreatable disease, and there is an urgent need to identify new drug targets. This work focuses on a particular biochemical pathway in the human malaria parasite, Plasmodium falcip ....Malaria is responsible for hundreds of millions of cases and an estimated 1.5-2.7 million deaths each year. The disease is caused by a microscopic parasite which is becoming increasingly resistant to antimalarial drugs. There is a very real possibility that there will soon be parts of the world in which malaria is an untreatable disease, and there is an urgent need to identify new drug targets. This work focuses on a particular biochemical pathway in the human malaria parasite, Plasmodium falciparum. The pathway mediates the conversion of the nutrient, vitamin B5, into a molecule called Coenzyme A. It plays an essential role in the intraerythrocytic parasite and our preliminary data indicate that components of this pathway hold significant potential as antimalarial drug targets. In this project we will use a range of biochemical and molecular biology approaches to characterise in detail the components of this pathway in the parasite and to explore the possibility that compounds that inhibit this pathway may be of value as much-needed new antimalarial agents.Read moreRead less
The Regulation Of Vitamin D-Dependent Bone Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$612,535.00
Summary
This project aims to establish the cellular basis for the importance of vitamin D in bone. This information is necessary to develop public health nutritional recommendations for improving in skeletal health and reducing the incidence of hip factures in the elderly. Furthermore our data have the potential to reveal novel activities of vitamin D that could eventuate as pharmacological targets.
In women there is a strong link between increased risk of breast cancer and low levels of vitamin D. We will use a novel explant system where breast tissue biopsies from women with breast cancer will be used to explore the metabolism of vitamin D and its consequences. This grant proposal will determine the dose of vitamin D that will provide a preventative strategy for breast cancer in the general population, and potential of vitamin D as an adjunct treatment in women with breast cancer.
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
Control Of Bone Remodelling By Osteoclastic Metabolism Of Vitamin D
Funder
National Health and Medical Research Council
Funding Amount
$694,635.00
Summary
Vitamin D is essential for bone health. This study will build on our extensive body of preliminary data to investigate the extent to which bone-resorbing osteoclasts are controlled by circulating levels of the pro-hormone 25-hydroxyvitamin D. Our work will identify new approaches to the treatment of osteoporosis, by targetting the osteoclast as a vitamin D-responsive cell type.
Autocrine Vitamin D Metabolism, Activity And Bone Health
Funder
National Health and Medical Research Council
Funding Amount
$459,270.00
Summary
This project will provide the detailed understanding of the activities of vitamin D within the bone microenvironment and offers the exciting prospect of elucidating the mechanistic reasons for maintaining an adequate vitamin D status in relation to the prevention of osteoporotic hip fractures. Thus, this project has great potential to improve community health by being able to recommend vitamin D supplementation made on the basis of maintaining normal bone cell function.