We have used mathematics and physical laws to make a model of how molecules, cells and tissues behave during development, especially describing how chiral molecules might give rise to twists that shape cells and tissues as embryos grow into fully developed organisms. We have made good progress in understanding how molecules move in large groups to shape how cells change over time. We have also achieved our goal to understand how cells push against each other to shape tissues during development. In terms of more specific results, we have reconstituted key aspects of actomyosin dynamics on supported lipid bilayers, for example a contractile instability that leads to symmetry breaking of actomyosin at larger scales and actomyosin foci patter formation. While this is a prerequisite for reconstituting chiral flows, we could not recreate consistent chiral flows in vitro as of yet. However, as part of our experiments we discovered dynamic cortical condensates, which are important for de novo actomyosin cortex formation. We were successful in reconstituting key aspects of their dynamics on supported lipid bilayers (under review, PNAS). With respect to chiral actomyosin dynamics and torque generation in vivo we have a) discovered that counter-rotating chiral flows are lineage-specific leading to a complex pattern of cell-cell arrangement, b) discovered that formin and myosin cooperate for actomyosin torque generation and that this interaction involves actomyosin foci, c) discovered that axis convergence in the nematode worm is driven by torque generation of actomyosin with respect to the C. elegans eggshell, and d) that the interaction between the actomyosin cortex and the spindle can lead to a similar mechanism of actomyosin torque generation, causing the axis of cell division even at later stages of development to align with the long axis of the C. elegans eggshell. Finally, we have established quail as a model system in the lab, and are in the final stages of preparation of a manuscript that reports on the discovery that the tissue rotation that underlies L/R symmetry breaking in avian embryo is driven by local torque generation at the node, requiring a mechanical connection to the underlying mesoderm and hypoblast tissue. Importantly, all these discoveries came about through close interaction between theory and experiment and involved developments on the side of active chiral fluid theory. In the quail cases, we pursued a discussion of active chiral fluid theory from the point of view of physical boundaries in what is typically referred to as crick physics. Dissemination of our work has proceeded very well through the publication of papers, the attendance of conferences, workshops and outreach events and using social media.
