Grant: Research Tools and Instruments - Category 1 (<$150,000)

We are investigating how the local tissue environment affects the behaviour of individual cells - their ability to divide, to relocate within the tissue, or to fulfil the unique functions inherent to their cell type. One factor that dramatically changes cell behaviour in this context is deprivation of oxygen ('hypoxia') and nutrients. In hypoxic tissues the energy metabolism of the cells is changed, and there is a dramatic release of certain chemicals that are involved in the energy supply cycle. One of the most important is adenosine, which our research has shown is able to alter cell proliferation, enhance the ability of cells to move, and modify the range of regulatory proteins that the cell has on its outer surface. This unassuming, simple regulator has probably played an important part in coordinating cell behaviour throughout much of evolution, and is important in human prenatal development, defence mechanisms and disease.   We showed some time ago that chronically hypoxic tissue has levels of adenosine that are about 100-fold higher than in normal tissues. However, our efforts since then, to measure the changes in adenosine in certain situations and to relate them to the changes we see, have been hampered by the lack of a reliable means of measuring this chemical. The equipment that we have received through this program will allow us to make a major leap forward, and to perform careful measurements not only of adenosine but also of other important metabolites. Not only will this help us in our understanding of a very fundamental process, but it will also enable us to move our work toward exploiting this phenomenon for scientific and therapeutic benefit.