Ben Larson
University of California, San Francisco & Berkeley
I use microscopes, math, and computation to understand how cells control shape and movement to thrive in various environments. During my undergraduate degree in physics at Reed College, I became increasingly interested in biology and biophysics. After a stint at the National Institutes of Health in a cell biology lab doing a lot of computational image analysis, I joined the Biophysics PhD Program at UC Berkeley. There, I worked in Nicole King’s lab on the evolution of multicellular morphogenesis by studying the cellular and biophysical mechanisms regulating 3D colony shape in choanoflagellates. In my postdoc in Wallace Marshall’s lab at UCSF, I am investigating the biophysical and computational principles by which cells control complex behaviors through studying locomotion and sensorimotor activity in ciliates and amoebae.
Regulation of form in multicellular choanoflagellates and the evolutionary cell biology of morphogenesis
Choanoflagellates, the closest living relatives of animals, can form multicellular colonies of various shapes and sizes. This diversity and the simplicity of multicellular forms in conjunction with their important phylogenetic position makes choanoflagellates an ideal system for studying the evolution of morphogenesis. Comparisons between the biology of choanoflagellates and animals has begun to shed light on animal origins. However, because most work has focused on genetics and genomics, little is known about the cellular and biophysical mechanisms underlying the regulation of multicellular form in choanoflagellates. Through the quantitative characterization of the biophysical processes underlying the development of rosette colonies in the choanoflagellate Salpingoeca rosetta, coupled with perturbative experiments and simulations, we found that that the basal extracellular matrix (ECM) secreted during rosette development exerts a physical constraint on the packing of proliferating cells, thereby sculpting morphogenesis. In addition, simulations yielded a morphospace for the shapes of multicellular colonies, consistent with observations across a range of choanoflagellates. Overall, our biophysical perspective complements previous genetic perspectives and thus helps illuminate the interplay between cell biology and physics in regulating morphogenesis. Another choanoflagellate, the recently discovered Choanoeca flexa, forms multicellular cup-shaped colonies. Colonies rapidly invert their curvature in response to changing light levels, which they detect through a rhodopsin-cGMP pathway. Inversion is mediated by cell shape changes requiring actomyosin-mediated apical contractility and allows alternation between feeding and swimming behavior. C. flexa thus rapidly converts sensory inputs directly into multicellular contractions. In this respect, it may inform reconstructions of hypothesized animal ancestors that existed before the evolution of specialized sensory and contractile cells.