One way cells respond to their environment is by creating internal signals that regulate gene expression. Human and yeast cells employ homologous signaling pathways to control cell growth, stress response, metabolic pathways and differentiation. Therefore, the relatively simple and genetically pliable budding and fission yeasts are valuable model organisms providing important insights to mechanisms of signal transduction in mammalian cells. My laboratory studies the glucose/cAMP signal pathway that is central to the transcriptional regulation of the fission yeast fbpl gene. Environmental glucose triggers the activation of adenylate cyclase, and the resulting cAMP signal activates protein kinase A to repress fbpI transcription. Many, but not all, of the genes we have identified in this pathway in fission yeast encode proteins whose human homologues carry out similar functions in cAMP signaling. Therefore this model system has the potential both to advance our structural understanding of conserved signaling mechanisms and to lead to novel discoveries. In addition, the catalytic domain of fission yeast adenylate cyclase enzyme closely resembles those of several pathogenic organisms including the human pathogens Trypanosoma brucei and Candida albicans. While the cAMP pathway appears to be important to growth and differentiation of these organisms, nothing is known about the regulation of their adenylate cyclase enzymes. Therefore, our studies may suggest potential targets for inhibiting the growth or invasiveness of these pathogens. We propose to continue our work on adenylate cyclase activation by conducting genetic, molecular and biochemical studies of the fission yeast glucose/cAMP pathway.
