Getting Together: What Can Enzyme Clustering Do for Metabolism?
Dr. Ned Wingreen
Department of Molecular Biology
Abstract: Metabolism is the set of enzymatic reactions that cells use to generate energy and biomass. Interestingly, recent studies suggest that many metabolic enzymes assemble into large clusters, often in response to environmental conditions. Theoretically, we find that large-scale enzyme clusters, with no internal spatial ordering of enzymes, offer many of the same advantages as direct substrate channeling: accelerating intermediate processing, protecting intermediates from degradation/cross-reactions, and protecting the cell from toxic intermediates. The model predicts the separation and size of coclusters that maximize metabolic efficiency. For direct validation, we study a metabolic branch point in Escherichia coli and experimentally confirm the model predictions. Our studies establish a quantitative framework to understand coclustering-mediated metabolic channeling and its application to both efficiency improvement and metabolic regulation.
Bio: Ned Wingreen received his Ph. D. in theoretical condensed matter physics from Cornell University in 1989. He did his postdoc in mesoscopic physics at MIT before moving, in 1991, to the newly founded NEC Research Institute in Princeton. At NEC, he continued to work in mesoscopic physics, but also started research on the statistical mechanics of protein folding. Thinking about proteins led him inexorably down the path into biology. During a sabbatical at UC Berkeley in 1999, his primary focus shifted to systems biology of bacteria. Wingreen joined Princeton University as a Professor of Molecular Biology in 2004, with a joint appointment in the Lewis-Sigler Institute as of 2008. Wingreen’s current research focuses on modeling intracellular networks in bacteria as well as bacterial communities.