Grant: Operating Grant

Regulated changes in cellular function underlie normal development in humans and in other organisms, and defects in these functions cause disease. For example, the biochemical mechanisms employed by proliferating cells to utilize essential nutrients (termed metabolism) contrasts with those used by non-dividing cells, and mis-regulation of metabolism causes cancerous cell growth. Moreover, the distinctive compartments that cells possess, called organelles, execute dramatic and stereotypical morphological transitions critical to human development and health. Model organisms have been utilized in the laboratory to investigate the molecular mechanisms controlling these and many other examples of cell physiology with great success. Recent work from my laboratory has described fundamental new aspects of the lifecycle of the budding yeast Saccharomyces cerevisiae, a powerful and widely exploited model organism. Both of these discoveries concern the gametogenesis phase of the yeast lifecycle, more commonly known as sporulation. Sporulation is a developmental program during which yeast, a single-celled microbe, exits the growth phase and produces dramatically remodeled and specialized cells called spores, which are analogous to gametes (sperm or egg) in humans. In addition to providing new insights into developmental programs employed by this widely studied model organism, the discovery of these phenomena expands the relevance of yeast to the understanding of the molecular and evolutionary underpinnings of human health and disease. Indeed, we have successfully extended some of our findings to test fundamental ideas concerning cancer using human cancer cells. Specifically, our findings illuminate unexpected and important conservation of mechanisms that govern metabolic reprogramming in human cancer cells and in yeast, highlighting yeast as a powerful model for further exploration of these mechanisms.