Synthetic biology is an emerging field that involves the engineering and re-design of organisms for purposes such as food security, health, and environmental protection. As such, it poses numerous ethical, legal, and social implications (ELSI) for researchers and policy makers. Various efforts to ensure socially responsible synthetic biology are underway. Policy making is one regulatory avenue, and other initiatives have sought to embed social scientists and ethicists on synthetic biology projects. However, given the nascency of synthetic biology, the number of heterogeneous domains it spans, and the open nature of many ethical questions, it has proven challenging to establish widespread concrete policies, and including social scientists and ethicists on synthetic biology teams has met with mixed success. This text proposes a different approach, asking instead is it possible to develop a well-performing recommender model based upon natural language processing (NLP) to connect synthetic biologists with information on the ELSI of their specific research? This recommender was developed as part of a larger project building a Synthetic Biology Knowledge System (SBKS) to accelerate disco
In this study, we explore how the combination of synthetic biology, neuroscience modeling, and neuromorphic electronic systems offers a new approach to creating an artificial system that mimics the natural sense of smell. We argue that a co-design approach offers significant advantages in replicating the complex dynamics of odor sensing and processing. We propose a hybrid system of synthetic sensory neurons that provides three key features: (a) receptor-gated ion channels, (b) interface between synthetic biology and semiconductors and (c) event-based encoding and computing based on spiking networks. Our approach is validated using simulation-based modeling of the complete sensing and processing pipeline. This research seeks to develop a platform for ultra-sensitive, specific, and energy-efficient odor detection, with potential implications for environmental monitoring, medical diagnostics, and security.
DNA cloning methods are fundamental tools in molecular biology, synthetic biology, and genetic engineering that enable precise DNA manipulation for various scientific and biotechnological applications. This review systematically summarizes the major restriction-free overlapping sequence cloning (RFOSC) techniques currently used in synthetic biology and examines their development, efficiency, practicality, and specific applications. In vitro methods, including Gibson Assembly, Circular Polymerase Extension Cloning (CPEC), Polymerase Incomplete Primer Extension (PIPE), Overlap Extension Cloning (OEC), Flap Endonuclease Cloning (FEN-Cloning), and commercially available techniques such as TOPO and In-Fusion, have been discussed alongside hybrid approaches such as Ligation-Independent Cloning (LIC), Sequence-Independent Cloning (SLIC), and T5 Exonuclease-Dependent Assembly (TEDA). Additionally, in vivo methods leveraging host recombination machinery, including Yeast Homologous Recombination (YHR), In Vivo Assembly (IVA), Transformation-Associated Recombination (TAR), and innovative approaches such as Multiple-Round In Vivo Site-Specific Assembly (MISSA) and Phage Enzyme-Assisted Direct
The convergence of artificial intelligence (AI) and synthetic biology is rapidly accelerating the pace of biological discovery and engineering. AI techniques, such as large language models and biological design tools, are enabling the automated design, build, test, and learning cycles for engineered biological systems. This convergence promises to democratize synthetic biology and unlock novel applications across domains from medicine to environmental sustainability. However, it also poses significant risks around reliability, dual use, and governance. The opacity of AI models, the deskilling of workforces, and the outdated nature of current regulatory frameworks present challenges in ensuring responsible development. Urgent attention is needed to update governance structures, integrate human oversight into increasingly automated workflows, and foster a culture of responsibility among the growing community of bioengineers. Only by proactively addressing these issues can we realize the transformative potential of AI-driven synthetic biology while mitigating its risks.
Synthetic biology is a recent area of biological engineering, whose aim is to provide cells with novel functionalities. A number of important results regarding the development of control circuits in synthetic biology have been achieved during the last decade. A differential geometry approach can be used for the analysis of said systems, which are often nonlinear. Here we demonstrate the application of such tools to analyse the structural identifiability, observability, accessibility, and controllability of several biomolecular systems. We focus on a set of synthetic circuits of current interest, which can perform several tasks, both in open loop and closed loop settings. We analyse their properties with our own methods and tools; further, we describe a new open-source implementation of the techniques.
AI-enabled synthetic biology has tremendous potential but also significantly increases biorisks and brings about a new set of dual use concerns. The picture is complicated given the vast innovations envisioned to emerge by combining emerging technologies, as AI-enabled synthetic biology potentially scales up bioengineering into industrial biomanufacturing. However, the literature review indicates that goals such as maintaining a reasonable scope for innovation, or more ambitiously to foster a huge bioeconomy don't necessarily contrast with biosafety, but need to go hand in hand. This paper presents a literature review of the issues and describes emerging frameworks for policy and practice that transverse the options of command-and control, stewardship, bottom-up, and laissez-faire governance. How to achieve early warning systems that enable prevention and mitigation of future AI-enabled biohazards from the lab, from deliberate misuse, or from the public realm, will constantly need to evolve, and adaptive, interactive approaches should emerge. Although biorisk is subject to an established governance regime, and scientists generally adhere to biosafety protocols, even experimental, b
Bacteria have been a source of inspiration for the design of evolutionary algorithms. At the beginning of the 20th century synthetic biology was born, a discipline whose goal is the design of biological systems that do not exist in nature, for example, programmable synthetic bacteria. In this paper, we introduce as a novelty the designing of evolutionary algorithms where all the steps are conducted by synthetic bacteria. To this end, we designed a genetic algorithm, which we have named BAGA, illustrating its utility solving simple instances of optimization problems such as function optimization, 0/1 knapsack problem, Hamiltonian path problem. The results obtained open the possibility of conceiving evolutionary algorithms inspired by principles, mechanisms and genetic circuits from synthetic biology. In summary, we can conclude that synthetic biology is a source of inspiration either for the design of evolutionary algorithms or for some of their steps, as shown by the results obtained in our simulation experiments.
The use of synthetic data has emerged as an essential tool in Magnetic Resonance Spectroscopy (MRS) research and applications, providing advantages for optimization of acquisition, software validation, deep learning applications, and enhanced reproducibility. Importantly, synthetic data addresses challenges of limited training data availability, particularly for clinical populations, and offers controlled solutions for investigating uncertainties and unexplained variance with in vivo data. This work provides a review and evaluation of current practices in the use and generation of synthetic data within the MRS field. Conducted by the MRS Synthetic Data Working Group under the Code & Data Sharing Committee of the MRS Study Group of the International Society for Magnetic Resonance in Medicine (ISMRM), this manuscript encompasses existing literature, supplemented by collective experience and in-house methodologies.
A central goal of synthetic biology is to design sophisticated synthetic cellular circuits that can perform complex computations and information processing tasks in response to specific inputs. The tremendous advances in our ability to understand and manipulate cellular information processing networks raises several fundamental physics questions: How do the molecular components of cellular circuits exploit energy consumption to improve information processing? Can one utilize ideas from thermodynamics to improve the design of synthetic cellular circuits and modules? Here, we summarize recent theoretical work addressing these questions. Energy consumption in cellular circuits serves five basic purposes: (1) increasing specificity, (2) manipulating dynamics, (3) reducing variability, (4) amplifying signal, and (5) erasing memory. We demonstrate these ideas using several simple examples and discuss the implications of these theoretical ideas for the emerging field of synthetic biology. We conclude by discussing how it may be possible to overcome these limitations using "post-translational" synthetic biology that exploits reversible protein modification.
Synthetic biologists have made great progress over the past decade in developing methods for modular assembly of genetic sequences and in engineering biological systems with a wide variety of functions in various contexts and organisms. However, current paradigms in the field entangle sequence and functionality in a manner that makes abstraction difficult, reduces engineering flexibility, and impairs predictability and design reuse. Functional Synthetic Biology aims to overcome these impediments by focusing the design of biological systems on function, rather than on sequence. This reorientation will decouple the engineering of biological devices from the specifics of how those devices are put to use, requiring both conceptual and organizational change, as well as supporting software tooling. Realizing this vision of Functional Synthetic Biology will allow more flexibility in how devices are used, more opportunity for reuse of devices and data, improvements in predictability, and reductions in technical risk and cost.
Synthetic biology is the engineering of cellular networks. It combines principles of engineering and the knowledge of biological networks to program the behavior of cells. Computational modeling techniques in conjunction with molecular biology techniques have been successful in constructing biological devices such as switches, oscillators, and gates. The ambition of synthetic biology is to construct complex systems from such fundamental devices, much in the same way electronic circuits are built from basic parts. As this ambition becomes a reality, engineering concepts such as interchangeable parts and encapsulation will find their way into biology. We realize that there is a need for computational tools that would support such engineering concepts in biology. As a solution, we have developed the software Athena that allows biological models to be constructed as modules. Modules can be connected to one another without altering the modules themselves. In addition, Athena houses various tools useful for designing synthetic networks including tools to perform simulations, automatically derive transcription rate expressions, and view and edit synthetic DNA sequences. New tools can be i
Silicon has striking similarity with carbon and is found in plant cells. However, there is no specific role that has been assigned to silicon in the life cycle of plants. The amount of silicon in plant cells is species specific and can reach levels comparable to macronutrients. Silicon is the central element for artificial intelligence, nanotechnology and digital revolution thus can act as an informational molecule like nucleic acids while the diverse bonding potential of silicon with different chemical species is analogous to carbon and thus can serve as a structural candidate such as proteins. The discovery of large amounts of silicon on Mars and the moon along with the recent developments of enzyme that can incorporate silicon into organic molecules has propelled the theory of creating silicon-based life. More recently, bacterial cytochrome has been modified through directed evolution such that it could cleave silicon-carbon bonds in organo-silicon compounds thus consolidating on the idea of utilizing silicon in biomolecules. In this article the potential of silicon-based life forms has been hypothesized along with the reasoning that autotrophic virus-like particles can be a luc
Building circuits and studying their behavior in cells is a major goal of systems and synthetic biology. Synthetic biology enables the precise control of cellular states for systems studies, the discovery of novel parts, control strategies, and interactions for the design of robust synthetic systems. To the best of our knowledge,there are no literature reports for the synthetic circuit construction for protozoan parasites. This paper describes the construction of genetic circuit for the targeted enzyme inositol phosphorylceramide synthase belonging to the protozoan parasite Leishmania. To explore the dynamic nature of the circuit designed, simulation was done followed by circuit validation by qualitative and quantitative approaches. The genetic circuit designed for inositol phosphorylceramide synthase shows responsiveness, oscillatory and bistable behavior, together with intrinsic robustness.
Self-driving labs (SDLs) combine fully automated experiments with artificial intelligence (AI) that decides the next set of experiments. Taken to their ultimate expression, SDLs could usher a new paradigm of scientific research, where the world is probed, interpreted, and explained by machines for human benefit. While there are functioning SDLs in the fields of chemistry and materials science, we contend that synthetic biology provides a unique opportunity since the genome provides a single target for affecting the incredibly wide repertoire of biological cell behavior. However, the level of investment required for the creation of biological SDLs is only warranted if directed towards solving difficult and enabling biological questions. Here, we discuss challenges and opportunities in creating SDLs for synthetic biology.
Synthetic Biology is the new engineering-based approach to biology that includes applications of designing complex biological devices. At present, it is not yet clear what will emerge as the defining principles of Synthetic Biology. One proposed approach is to build Synthetic Biology around the classical engineering principles of standardization, modularity/decoupling and abstraction/modeling to facilitate component-based design. In this article we suggest and discuss an alternative paradigm, which we call High-throughput Biologically Optimized Search Engineering (HT-BOSE). Stemming from directed evolution, in HT-BOSE the focal point is a biological knowledge based rational optimization of the search process in the space of device design possibilities. The HT-BOSE approach may also be relevant in other contexts and we briefly highlight how it could be applicable to the development of multi-drug cocktails in a biomedical setting.
Biology has changed radically in the last two decades, transitioning from a descriptive science into a design science. Synthetic biology allows us to bioengineer cells to synthesize novel valuable molecules such as renewable biofuels or anticancer drugs. However, traditional synthetic biology approaches involve ad-hoc engineering practices, which lead to long development times. Here, we present the Automated Recommendation Tool (ART), a tool that leverages machine learning and probabilistic modeling techniques to guide synthetic biology in a systematic fashion, without the need for a full mechanistic understanding of the biological system. Using sampling-based optimization, ART provides a set of recommended strains to be built in the next engineering cycle, alongside probabilistic predictions of their production levels. We demonstrate the capabilities of ART on simulated data sets, as well as experimental data from real metabolic engineering projects producing renewable biofuels, hoppy flavored beer without hops, and fatty acids. Finally, we discuss the limitations of this approach, and the practical consequences of the underlying assumptions failing.
This technical monograph provides a comprehensive overview of the field of quantum biology. It approaches quantum biology from a physical perspective with core quantum mechanical concepts presented foremost to provide a theoretical foundation for the field. An extensive body of research is covered to clarify the significance of quantum biology as a scientific field, outlining the field's long-standing importance in the historical development of quantum theory. This lays the essential groundwork to enable further advances in nanomedicine and biotechnology. Written for academics, biological science researchers, physicists, biochemists, medical technologists, and students of quantum mechanics, this text brings clarity to fundamental advances being made in the emerging science of quantum biology.
This article frames the relation between biology and physics by characterizing the former as a subdiscipline rather than a special case of the latter. To do this, we posit biological physics as the science of living matter in contrast to classic biophysics, the study of organismal properties by physical techniques. At the scale of the individual cell, living matter is nonunitary, i.e., not composed of aggregated subunits, and has features (e.g., intracellular organizational arrangements and biomolecular condensates) that are unlike any materials of the nonliving world. In transiently or constitutively multicellular forms (social microorganisms, animals, plants), living matter sustains physical processes that are generic (shared with nonliving matter, e.g., subunit communication by molecular diffusion in cellular slime molds), biogeneric (analogous to nonliving matter but realized through cellular activities, e.g., subunit demixing in animal embryos) or nongeneric (pertaining to sui generis materials, e.g., budding of active solids in plants). This "forms of matter" perspective is philosophically situated in the dialectical materialism of Engels and Hessen and the multilevel physica
Computer-aided design for synthetic biology promises to accelerate the rational and robust engineering of biological systems; it requires both detailed and quantitative mathematical and experimental models of the processes to (re)design, and software and tools for genetic engineering and DNA assembly. Ultimately, the increased precision in the design phase will have a dramatic impact on the production of designer cells and organisms with bespoke functions and increased modularity. Computer-aided design strategies require quantitative representations of cells, able to capture multiscale processes and link genotypes to phenotypes. Here, we present a perspective on how whole-cell, multiscale models could transform design-build-test-learn cycles in synthetic biology. We show how these models could significantly aid in the design and learn phases while reducing experimental testing by presenting case studies spanning from genome minimization to cell-free systems, and we discuss several challenges for the realization of our vision. The possibility to describe and build in silico whole-cells offers an opportunity to develop increasingly automatized, precise and accessible computer-aided d
Synthetic biology is one of the battlefields where the main countries fight for the supremacy in science. The word synthetic biology hides a big world, ready to be explored by interdisciplinary research collaborations. The purpose of this investigation is to reveal the what, where, when of the current situation in this emerging field. A keyword search string for the field was constructed and applied in the Web of Science and in the Derwent Innovations Index. In particular, we calculated year based h-type indices for high-frequent keywords.