Grant: Project Grant

There are several lines of evidence to suggest that silicon (Si) is important for the proper functioning of many tissues. In particular, Si is believed to provide resiliency to bone and prevent the premature aging of arteries, that is, of atherosclerosis. We have recently identified Si transporters in human for the first time and feel that this discovery should enable us to study the biological role of Si in much greater detail than before. The purpose of our proposal will be in fact to determine the functional and operational characteristics of the recently uncovered Si transporters. One group of transporters is called the aquaglyceroporins. These proteins are also specialized in the facilitated movement of water and alternative substrates such as urea into and/or out of cells. The other group includes transporters of unknown function and is called organic anion exchanger "x". The purpose of our proposal will also be to determine the biological relevance of Si transport by these proteins in Si-rich tissues such as bone and the arterial vessel wall. Our main research questions will be addressed by carrying out transport studies in primary culture cells derived from bone tissues and arterial conduits as well as physiological studies in isolated arterial vessels, bone explants and whole animals. We should be able to show that when isolated cells and tissues are deprived of Si through various means, their normal responses to a variety of environmental cues are perturbed. We should also be able to show that the changes observed translate into deleterious abnormalities in vivo. Through the efforts proposed, our hope is to identify novel molecular targets for the prevention of common diseases such as osteoporosis and atherosclerosis. Based on the wealth of preliminary data that we have generated, we believe that our chance of success is very high.