With a background in theoretical condensed matter physics, Simons’ current research interests focus on the application of quantitative statistical approaches to the study of biological processes at the subcellular, cellular and organ scale. In particular, he has developed analytical schemes to resolve the dynamics and fate behaviour of stem and progenitor cell populations in the development, maintenance and repair of adult tissues, and factors leading to their dysregulation in diseased states. Following a period of post-doctoral training at MIT, in 1995 Simons took up a faculty position at the Cavendish Laboratory, Department of Physics in Cambridge, where he currently holds the Herchel Smith Chair in Physics. He is also an Associate Group Leader at the Wellcome Trust/Cancer Research UK Gurdon Institute and a PI at the Cambridge Stem Cell Institute.
A unifying theory of branching morphogenesis
Branching morphogenesis has been a subject of abiding interest. Although much is known about the underlying signaling pathways, it remains unclear how the macroscopic features of branched organs, including their size, network topology and spatial patterning, are encoded. Here we show that, in the mouse mammary gland, kidney, pancreas and human prostate, these features can be explained quantitatively within a single unifying framework of branching and annihilating random walks. Based on large-scale organ reconstructions, genetic lineage tracing and proliferation kinetics, we show that morphogenesis follows from the collective proliferative activity of equipotent progenitor pools localized at ductal tips that drive a process of ductal elongation and stochastic tip bifurcation. By correlating cell cycle exit with proximity to maturing ducts, this dynamics results in the specification of a complex network of defined density and statistical organization. These results show that branched epithelial structures in mammalian tissues develop as a self-organized process, reliant upon a strikingly simple, but generic, set of local rules, without recourse to a rigid and deterministic sequence of genetically programmed events.