Regulation Of Lysosomal Proteases By The Intracellular Serpin, PI-6.
Funder
National Health and Medical Research Council
Funding Amount
$152,500.00
Summary
All cells have a graded response to stress. At low levels of stress, intrinsic systems counter the stressor and repair damage. As stress increases and irreparable damage is likely, affected cells suicide in a pre-programmed manner, and are rapidly engulfed by their neighbours to prevent initiation of a deleterious inflammatory response. Finally, if subjected to overwhelming stress, cells may burst and trigger an inflammatory response. Emerging evidence shows that several organelles in the cell a ....All cells have a graded response to stress. At low levels of stress, intrinsic systems counter the stressor and repair damage. As stress increases and irreparable damage is likely, affected cells suicide in a pre-programmed manner, and are rapidly engulfed by their neighbours to prevent initiation of a deleterious inflammatory response. Finally, if subjected to overwhelming stress, cells may burst and trigger an inflammatory response. Emerging evidence shows that several organelles in the cell act as stress sensors and participate in initiating programmed cell death. In particular, it appears that degradative enzymes (proteases) released under stress from waste disposal-recycling organelles (lysosomes) can induce death. This may occur in settings such as infection or cardiovascular disease (e.g. stroke). As part of a defence mechanism to counter low level release of these lysosomal proteases, we propose that some cells produce inhibitors called serpins. In preliminary work we have shown that particular serpins do indeed inactivate a subset lysosomal proteases. We propose to study the role of these serpins in protecting cultured cells from stress and the effects of lysosomal protease release. In addition, we will use mice lacking one of these serpins to evaluate its importance in the physiological response to stresses such as bacterial and viral infection, tumor formation and stroke.Read moreRead less
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.
Vitamin D And Genetic Susceptibility In Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$122,714.00
Summary
Vitamin D3 levels appear to predict clinical status in multiple sclerosis. The reasons for this are unclear, but may be linked to the effect of the Vitamin D Receptor (VDR) on a subset of immune cells. This project aims to identify key genes which are regulated by this receptor, by using specific gene sequencing technologies combined with knowledge of the genes which confer risk of developing MS. This may help to identify the molecular pathways underlying MS and potential treatment strategies.
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.
Roles Of Vitamin D In Skeletal Muscle And Satellite Cells
Funder
National Health and Medical Research Council
Funding Amount
$380,891.00
Summary
Vitamin D deficiency leads to muscle pain and weakness that are reversible with vitamin D supplementation. However, precise biological effects of vitamin D in skeletal muscle are unclear. In this fellowship, novel mouse models and innovative techniques will be used to examine vitamin D signalling pathways in whole muscle and muscle stem cells. Ultimately, the therapeutic potential of the vitamin D pathway in treatment of muscle disorders and age-related muscle wasting will be explored.
Quantitiative Assessment Of Solar UV Exposure For Vitamin D Synthesis In Australian Adults
Funder
National Health and Medical Research Council
Funding Amount
$1,162,536.00
Summary
This research program will add significantly to our current scientific understanding of the dual health outcomes of UV exposure (Vitamin D and skin cancer) . This project is in line with Australia's R and D Priorities, in that it will result in direct and indirect social and economic benefits to Australia by applying the scientific knowledge gained through this research to develop public health initiatives to improve some of Australia's most significant and costly health problems.