Some members of a group of common cell surface receptors called the G protein coupled receptors, or GPCRs, can be stimulated by several activating molecules that appear dissimilar. It is not understood how a single receptor recognizes several seemingly different activators, or if the receptor simply cannot differentiate between them. Evidence to date suggests that subtle differences in activators can, in fact, be detected by these receptors. This project will explore how the receptors recognize their multiple activators. A set of GPCRs and their pheromone activators, derived from the mushroom fungus Schizophyllum commune, will be used as an experimental model. Small, discrete changes will be made in the receptors and pheromones in order to identify areas within these molecules that are important for determining their mutual and specific recognition. New information gained from studying these receptors and pheromones will have implications for understanding the same type of receptors in other organisms, where less is known about one or the other partner. Both receptors and pheromones will be studied using molecular genetic techniques with an emphasis on recombinant DNA technology. Another genetic model fungus, the baker's yeast Saccharomyces cerevisiae, will be employed as a surrogate organism in which to test the changes made in the mushroom's receptors and pheromones because this yeast can be grown and manipulated with great efficiency. The impact of this basic biological research is potentially great. S. commune uses its receptors and pheromones to recognize compatible mating partners, while similarly complex sets of receptors and activators are the basis of taste and smell in animals and humans and, additionally, mating behavior in some animals. A large percentage of pharmaceuticals target GPCRs, thus a better general understanding of how GPCRs function will be of benefit for understanding drug action and design. An S. commune collection currently being submitted to the Fungal Genetic Stock Center at Kansas University will provide a genetic resource for further studies on these receptors and pheromones. In addition, this project will provide opportunities for undergraduate students to receive hands-on training in modern genetics, molecular genetics, and microbiology.
