Systems Biology of Glucose Metabolism In Humanized Yeast

One of the most remarkable characteristics of living systems is their ability to respond to stimuli. Sensing stimuli, transmitting the information to invoke appropriate response is largely carried out by specific signal transduction pathways, which are activated/deactivated by reversible phosphorylation. In this presentation, I will demonstrate how the information flux can be engineered to influence metabolic flux.

I will present the progress we made in our understanding of the signal transduction pathways that control and coordinate metabolism with growth and cellular processes. Specifically, I will focus on the signaling pathway that is controlled by Snf1 kinase, a highly conserved global regulator. This kinase controls energy homeostasis, regulates glucose metabolism and lipid synthesis as well as coordinates these processes with cell growth. Indeed, the homolog of this kinase is the target for diabetes drugs in the market today. The metabolic pathways as well as their regulation are largely conserved between humans and yeast, enabling this microorganism to serve as a prototype to gain deeper insight into metabolic malfunction in humans. In yeast, we determined the activation of Snf1, its interaction with other key kinases and the evolution of this interaction network as well as the consequences of its replacement with its mammalian counterpart. We discovered that the mammalian kinase was less efficient in regulating biosynthesis of amino acid and lipid biosynthesis in yeast. I will end with a perspective on the implications of our findings on engineering signaling pathways to manipulate metabolic flux.