Explaining the robustness and flexibility of embryo patterning using flies, beetles, fish, and computers (360G-Wellcome-227306_Z_23_Z)

To turn a fertilised egg into an adult organism, intricate patterns of cell differentiation must emerge from an initially simple and uniform state. This process, embryo patterning, is robust (withstands perturbation), scalable (adapts proportionally to embryo size), and flexible (produces different outputs in different species). Prevailing mathematical theories of patterning struggle to account for these properties, indicating a serious mismatch with biological reality. What is lacking, in my view, is an understanding of how the sophisticated gene regulatory networks inside cells exploit information exchange between cells to generate pattern regulation at the level of the whole tissue. I will study this question by interrogating anteroposterior (head-tail) patterning networks in model organisms, first the relatively simple Drosophila embryo, and later the more complicated embryos of Tribolium (a beetle) and zebrafish. For each species, I aim to (1) resolve the structure of the gene regulatory network responsible for patterning, (2) explain the mechanistic basis for its robustness, and (3) determine its control parameters and constraints. My research approach will combine quantitative imaging, genetic perturbations, and computational modelling. This work will advance our basic understanding of embryonic development, which facilitates progress in the treatment of developmental disease and the development of regenerative technologies.