Complex dynamical fluctuations, from intracellular noise, brain dynamics or computer traffic display bursting dynamics consistent with a critical state between order and disorder. Living close to the critical point has adaptive advantages and it has been conjectured that evolution could select these critical states. Is this the case of living cells? A system can poise itself close to the critical point by means of the so-called self-organized criticality (SOC). In this paper we present an engineered gene network displaying SOC behaviour. This is achieved by exploiting the saturation of the proteolytic degradation machinery in E. coli cells by means of a negative feedback loop that reduces congestion. Our critical motif is built from a two-gene circuit, where SOC can be successfully implemented. The potential implications for both cellular dynamics and behaviour are discussed.

Multicellularity is one of the major evolutionary transitions, and its rise provided the ingredients for the emergence of a biosphere inhabited by complex organisms. Over the last decades, the potential for bioengineering multicellular systems has been instrumental in interrogating nature and exploring novel paths to regeneration, disease, cognition, and behaviour. Here, we provide a list of open problems that encapsulate many of the ongoing and future challenges in the field and suggest conceptual approaches that may facilitate progress.

The study of ecosystems, both natural and artificial, has historically been mediated by population dynamics theories. In this framework, quantifying population numbers and related variables (associated with metabolism or biological-environmental interactions) plays a central role in measuring and predicting system-level properties. As we move toward advanced technological engineering of cells and organisms, the possibility of bioengineering ecosystems (from the gut microbiome to wildlands) opens several questions that will require quantitative models to find answers. Here, we present a comprehensive survey of quantitative modeling approaches for managing three kinds of synthetic ecosystems, sharing the presence of engineered strains. These include test tube examples of ecosystems hosting a relatively low number of interacting species, mesoscale closed ecosystems (or ecospheres), and macro-scale, engineered ecosystems. The potential outcomes of synthetic ecosystem designs and their limits will be relevant to different disciplines, including biomedical engineering, astrobiology, space exploration and fighting climate change impacts on endangered ecosystems. We propose a space of possible ecosystems that captures this broad range of scenarios and a tentative roadmap for open problems and further exploration.

Cognition is often associated with complex brains, yet many forms of learning─such as habituation, sensitization, and even spacing effects─have been observed in single cells and aneural organisms. These simple cognitive abilities, despite their cost, offer evolutionary advantages by allowing organisms to reduce environmental uncertainty and improve survival. Recent studies have confirmed early claims of learning-like behavior in protists and slime molds, pointing to the presence of basal cognitive functions long before the emergence of nervous systems. In this work, we adopt a synthetic biology approach to explore how minimal genetic circuits can implement nonassociative learning in unicellular systems. Building on theoretical models and using well-characterized regulatory elements, we design and simulate synthetic circuits capable of reproducing habituation, sensitization, and the massed-spaced learning effect. Our designs incorporate activators, repressors, fluorescent reporters, and quorum-sensing molecules, offering a platform for experimental validation. By examining the structural and dynamical constraints of these circuits, we highlight the distinct temporal dynamics of gene-based learning systems compared to neural counterparts and provide insights into the evolutionary and engineering challenges of building synthetic cognitive behavior at the cellular level.

Living systems have evolved cognitive complexity to reduce environmental uncertainty, enabling them to predict and prepare for future conditions. Anticipation, distinct from simple prediction, involves active adaptation before an event occurs and is a key feature of both neural and aneural biological agents. Building on the moving average convergence–divergence principle from financial trend analysis, we propose an implementation of anticipation through synthetic biology by designing and evaluating experimentally testable minimal genetic circuits capable of anticipating environmental trends. Through deterministic and stochastic analyses, we demonstrate that these motifs achieve robust anticipatory responses under a wide range of conditions. Our findings suggest that simple genetic circuits could be naturally exploited by cells to prepare for future events, providing a foundation for engineering predictive biological systems.

Living systems have evolved cognitive complexity to reduce environmental uncertainty, enabling them to predict and prepare for future conditions. Anticipation, distinct from simple prediction, involves active adaptation before an event occurs and is a key feature of both neural and aneural biological agents. Building on the moving average convergence–divergence principle from financial trend analysis, we propose an implementation of anticipation through synthetic biology by designing and evaluating experimentally testable minimal genetic circuits capable of anticipating environmental trends. Through deterministic and stochastic analyses, we demonstrate that these motifs achieve robust anticipatory responses under a wide range of conditions. Our findings suggest that simple genetic circuits could be naturally exploited by cells to prepare for future events, providing a foundation for engineering predictive biological systems.