Generative models of morphogenesis in developmental biology.

Understanding the mechanism by which cells coordinate their differentiation and migration is critical to our understanding of many fundamental processes such as wound healing, disease progression, and developmental biology. Mathematical models have been an essential tool for testing and developing our understanding, such as models of cells as soft spherical particles, reaction-diffusion systems that couple cell movement to environmental factors, and multi-scale multi-physics simulations that combine bottom-up rule-based models with continuum laws. However, mathematical models can often be loosely related to data or have so many parameters that model behaviour is weakly constrained. Recent methods in machine learning introduce new means by which models can be derived and deployed. In this review, we discuss examples of mathematical models of aspects of developmental biology, such as cell migration, and how these models can be combined with these recent machine learning methods.

Toward Engineering Biosystems With Emergent Collective Functions.

Many complex behaviors in biological systems emerge from large populations of interacting molecules or cells, generating functions that go beyond the capabilities of the individual parts. Such collective phenomena are of great interest to bioengineers due to their robustness and scalability. However, engineering emergent collective functions is difficult because they arise as a consequence of complex multi-level feedback, which often spans many length-scales. Here, we present a perspective on how some of these challenges could be overcome by using multi-agent modeling as a design framework within synthetic biology. Using case studies covering the construction of synthetic ecologies to biological computation and synthetic cellularity, we show how multi-agent modeling can capture the core features of complex multi-scale systems and provide novel insights into the underlying mechanisms which guide emergent functionalities across scales. The ability to unravel design rules underpinning these behaviors offers a means to take synthetic biology beyond single molecules or cells and toward the creation of systems with functions that can only emerge from collectives at multiple scales.