Grant: Operating Grant

Hormones are chemicals that circulate within the body and trigger specific responses in target tissues. Steroids, such as the estrogens used to treat or postpone menopause and the muscle building steroids taken by some athletes, are some well known examples. These particular hormones penetrate cells and elicit responses by binding to a family of proteins called nuclear receptors (NRs). NRs control many of the metabolic pathways in our body as well as related processes such as memory, behaviour and aging. Consequently, a large number of human diseases, for example diabetes, obesity, heart disease and Alzheimers, are caused, or enhanced, by NR malfunctions. Fortunately, the ability of these proteins to respond to small molecules that move efficiently within the body make them ideal drug targets. In fact, a disproportionate percentage of the most successful and important pharmaceuticals target specific NRs. This is despite the fact that hormone partners have yet to be identified for more than half of NRs. We have devised new methods to identify new human hormones using live fish. These methods allow us to screen chemical libraries for hormones that act in specific cells or tissues, that do not cross-react with other NRs, and that do not cause detrimental side effects. These are common problems in drug discovery that usually only come to light later during lengthy and costly clinical trials. These advantages will provide us with enormous advantages in terms of time, costs and successful compound identification.