Building a SynCell from molecular components is a staggering aim that involves a broad range of scientific challenges. However, the field is still in an explorative phase, and the approach and even the ultimate goal are not unanimously agreed upon1. Building SynCells from the ground up is a highly multidisciplinary undertaking requiring international collaborations. To this end, 36 senior scientists and 12 promising junior researchers from all around the globe gathered in Shenzhen, China, in October 2024, for the inaugural ‘SynCell Global Summit’. For the first time, this meeting brought together scientists from SynCell communities in Africa, Asia, Australia, Europe and the US. The attendees engaged in extensive discussions on challenging ideas, debated the limitations of the current approaches and worked towards establishing a consensus on the future direction of SynCell research. Researchers presented their initiatives, biofoundries, and funding programs, collectively striving to shape a unified vision for advancing the field. This article provides a brief overview of the outcomes of the summit on SynCell state-of-the-art research, major scientific challenges, and proposes synergistic efforts for the advancement of the field.
The bottom-up approach to SynCells: many benefits
There are diverse motivations for building a SynCell. For some, the drive stems from understanding, in a simplified context, the intricate processes found in living cells2 and from probing origins-of-life theories3. Others view SynCells as minimal and well controllable biomimetic systems with augmented chemistries and functions for applications in therapeutics4, energy production5, and biomanufacturing6. Notably, the SynCell community is inspired by the possibility of creating a living system, characterized by the ability to self-reproduce and evolve, from non-living building blocks. If so, the minimal conditions to “reboot” cellular life can test our fundamental understanding of life and its basic unit, the cell.
The term “SynCell” is often used for engineered cell-sized systems capable of performing life-like functions, such as information processing, motility, growth and division, signaling, or metabolism (Fig. 1a)7. Alternatively, it can be defined as a physicochemical system that sustains itself and replicates in an environment capable of open-ended evolution (Fig. 1b)8. The first definition emphasizes a modular approach to reconstituting all the biological features, excluding replication and evolution, while the second definition emphasizes the ability of a fully interoperable SynCell to replicate and evolve, which is key in addressing the fundamental evolution of life.
Fig. 1: Synthetic Cells. a Modular approach to SynCells with structural and functional modules represented (top) and main applications of SynCells (bottom). b Key functional characteristics for the realization of living SynCells. Full size image
Given the multidisciplinary challenge of building SynCells and their far-reaching potential impact, it is critical to promote global collaborations while striking a balance between exploration and unification of modules. The field will benefit from exploring different approaches, rather than be divided by definitions.
Current achievements in SynCell research
SynCells are far less complex than biological cells, however to date, only a few cellular functions have been reconstructed outside of the cellular context with much work still needed to achieve fully integrated systems7. Their exact nature (i.e., structure and function) varies greatly from SynCell to SynCell and is dictated by which life-like property is reconstructed, and in turn, which structural chassis has been chosen to facilitate it. However, key properties of living cells often involve compartmentalization and the coupling of genotype and phenotype through information processing. Therefore, the bottom-up approach to mimicking cellular functions typically comprises the use of molecular building blocks such as membranes, genetic material, and proteins. For example, taking inspiration from cell membranes, phospholipids to create lipid vesicles are widely used as an approach to creating SynCell structural chassis9. Other explored approaches include emulsion droplets10, liquid-liquid phase separated systems11, proteinosomes12, or hydrogels13.
Moreover, an essential cornerstone of cellular function is the coupling of genotype with phenotype. To this end, the assembly of transcription-translation (TX-TL) systems has been widely explored, either based on cellular extracts or reconstructed from purified components14,15, and then further integrated with compartmentalization to achieve SynCells programmed to communicate16, as well as interact with living cells17.
Furthermore, efforts in creating SynCells stretch beyond compartmentalization and information processing and include the engineering of systems capable other life-like features, such as self-powering18,19, self-propelling20,21, as well as partially regenerating their own components22.
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