2014 Franklin medal and prize

Professor Benjamin Simons, University of Cambridge. For the application of non-equilibrium statistical mechanics to provide fundamental new insights into the mechanisms that regulate stem cell behaviour in tissue maintenance and disease

Maxwell Lesanovsky

Ben Simons’ work on correlated electron systems, ultracold atom physics, semiconductors, mesoscopic physics, and quantum chaos is highly admired. During the last decade however, his research has extended to biology, with emphasis on stem cells. Tissue maintenance and repair relies upon these stem cells, which differentiate into more specialized cell types while retaining their self-renewal capacity. In homeostasis, stem cells must divide with precisely one half of their progeny remaining in the stem cell compartment while the other half differentiates. Most studies have focused on resolving factors that promote fate asymmetry in individual stem cells. However, asymmetry may also be achieved at the population level by balancing stem cell loss with duplication, leading to a continual depletion in clonal diversity.

Working closely with leading experimental labs and prompted by the key observation of scaling behaviour in clone size distributions, Simons has used insights from non-equilibrium statistical mechanics to elucidate patterns of stem cell fate. His studies showed that strategies of stem cell self-renewal can be separated into four “universality classes”, according to whether balance is achieved at the level of individual stem cells or the population, and whether regulation follows from intrinsic (cell-autonomous) processes or is mediated by signals from the local microenvironment. By combining long-term lineage tracing studies with marker-based assays, he has shown that the majority tissues conform to population asymmetric self-renewal, overturning paradigms long-held in the literature, and raising important questions about the mechanisms regulating stochastic fate.

Simons’ current research has extended these approaches to the study of non-homeostatic systems, from the late-stage development of tissues, to the pathways that promote tumour-initiation and disease. A clearer picture of the role of stem cell populations in tumour evolution is emerging.

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