Informal Seminar - Dr. Jake Cornwall-Scoones

"Bridging scales in developmental patterning"

The question of how embryos self-generate complex body parts, and do so perfectly almost all the time, has occupied developmental biologists for decades. Key to the establishment of the body plan is the generation and positioning of the right cell types at the right place, time and proportion: the process of developmental patterning. In this talk, I consider three case studies from my own work that seek a compromise between two schools of thought for how developmental patterning is achieved, namely hierarchical "instruction" and self-organisation. I will first explore how the coupling of boundary conditions and a self-organised Turing system can help rationalise the diversity of digit morphologies among tetrapods, and their often esoteric failure modes. I will then show how we can quantitatively explain, predict and engineer the behaviour of morphogen-dependent cis-regulatory elements (CREs) by combining interpretable statistical modelling with high-throughput combinatorial CRE construction, and how this can be used to re-engineer neural patterning. Finally, I will explore how the mechanical properties of tissues can both enable and constrain the appropriate positioning of an embryonic "organiser". Together, I hope to present a case for how guided self-organisation is a useful conceptual framework to rationalise developmental patterning, where intrinsic self-organising mechanisms are delimited, directed or diverted by upstream signals, mechanical constraints and boundary conditions. And how the constructionist science of generative biology provides a useful way in to tackle these questions.

Bio: Jake obtained his BA at the University of Cambridge, where he specialised in developmental biology, working on mechanisms of joint patterning in the digits of tetrapods. After graduating, he worked on mammalian cell polarity and self-organisation in ‘stembryo' models at the California Institute of Technology (Zernicka-Goetz and Thomson labs). For his PhD at the Francis Crick Institute (Briscoe lab), supported by Boehringer Ingelheim Fonds, Jake has established methods to generate synthetic morphogen-responsive cis-regulatory elements at scale, revealing modular design rules that enable predictable engineering of neural patterning. In addition, through a series of theory-experiment collaborations, he has established agent-based theoretical frameworks of morphogenesis and cellular differentiation.

Supported by the Schmidt Science Fellowship, Wolfson Junior Research Fellowship and Isaac Newton Trust, Jake's postdoctoral research between the labs of Steve Wilson, Ben Simons and Caren Norden will use zebrafish developmental genetics and theoretical approaches to investigate the mechanisms by which organs measure and regulate their sizes.

Host: Magda Zernicka-Goetz