Re-engineering symmetry breaking in development and evolution

Scientists have long sought to understand how complex multicellular organisms generate their final form. Yet despite considerable progress, demonstrating predictive knowledge sufficient to re-engineer development according to design, remains a grand challenge. Addressing this challenge is not only fundamentally important, but also critical to the future of regenerative medicine and agriculture. Development depends on coordinated symmetry breaking events resulting from diverse mechanisms, ranging from the asymmetric localisation of molecules and stochastic processes within cells to the formation of morphogen gradients across a tissue. A mechanistic understanding of complex patterning processes therefore requires gaining knowledge on the molecular basis of multiple types of symmetry breaking events occurring at different scales. RESYDE will address this challenge by integrating information from diverse approaches into a virtual, dynamic cellular template. Predictive modelling will then be used to explain symmetry breaking at different scales sufficient to re-engineer the system by design. We will use the Arabidopsis flower as a model system and apply an interdisciplinary approach that utilises fine-scale perturbation techniques together with in vivo live-imaging of key regulators along with spatially mapped multi omics data, hormonal gradients and tissue mechanics to monitor responses at multiple scales. To leverage these data we will establish a 4D virtual cell template together with multiscale models to generate and simulate hypotheses in silico on the precise molecular origins of symmetry breaking events within the flower. We will apply our knowledge using a re-engineering approach to alter multiple floral symmetry breaking processes to better understand evolutionary floral architectural changes. Ultimately, RESYDE will provide a fundamental step change in our understanding of concerted symmetry breaking events across scales in complex multicellular contexts.