"Artificial biology" was originally suggested as a term to refer to research aiming at design and synthesis of life-like systems from non-living matter (Benner et al., 2011). The research field is now more commonly known as "bottom-up synthetic biology" (Jia & Schwille, 2019; Rothschild et al., 2024) and is highly active with several international initiatives aimed at constructing synthetic cells bottom-up (e.g. Build-A-Cell and SynCell). By constructing life from scratch, this research addresses fundamental questions about what constitutes life, what is the likely origin of life on Earth, and can life exist in other forms in the universe. The research goal of synthesizing life is maybe overly ambitious, but the pursuit will as a side product lead to technological developments and innovations that may have important applications in biotechnology, medicine, and materials science.
"Artificial biology" is an interdisciplinary field that builds on decades of research in e.g., biophysics, origins of life, artificial life, systems chemistry, and bionanotechnology. Recent research has brought us closer than ever to creating synthetic life by constructing chemical, RNA, or cell-free systems that undergo Darwinian evolution (Ottelé et al., 2020; Joyce, 2009; Ueda et al., 2023), and by building synthetic cells with components designed using protein design and DNA or RNA nanotechnology (Zhan et al., 2022). Aarhus University researchers are contributing to this field by developing artificial cells and micromotors (Westensee et al., 2024; Docampo et al., 2024), artificial enzymes and receptors (Montasell et al., 2022; Søgaard et al., 2023), evolving novel RNA functions (Valero et al., 2021), designing RNA machines (Vallina et al., 2024), and studying RNA-catalyzed replication in an RNA world (McRae et al., 2024; Kristoffersen et al., 2025). iNANO has "synthetic biology" as a strategic research area (iNANO link), been home to several centers in related areas (iNANO link), and hosted the Artificial Biology conference in 2022 and 2024 (ArtBio). However, to accelerate the research further an integration of the different research efforts is needed.
The AUNAB network will explore "artificial biology" by taking its point of departure in the classical NASA definition of life that states: “Life is a self-sustaining chemical system capable of Darwinian evolution” (NASA link). The definition will be investigated by taking an engineering approach in the spirit of Richard Feynman quote "What I cannot create, I do not understand". The time is ripe for taking on the grand challenge of synthesizing life bottom-up, since several advanced methods and technologies are at our disposal, examples being computational methods (incl. machine learning) to design novel biomolecular structures, advanced high-throughput chemical synthesis approaches, and advanced characterization methods such as cryo-electron microscopy that allow us to study the native structure of complex molecular assemblies. We will investigate fundamental properties of life by exploring the engineering of (1) compartments and division, (2) replication and evolution, (3) enzymes and metabolism, (4) molecular machines and regulation, and finally (5) how to integrate these elements in synthetic cells. To widen the perspective, we will discuss synthetic life in the context of science history, bioethics, literature and art, design theory, and the search for life in space.
The "artificial biology" topic is truly interdisciplinary in nature, since the exploration of the fundamental properties of life by an engineering approach involves theory and experimental approaches from both chemistry, physics, molecular biology, engineering, and computer science. The interdisciplinarity extends beyond the natural sciences into literature and art, since this topic has captivated our imagination for centuries, and into sociology and ethics, since it - if fully realized - will have far reaching implications for society. Because we are getting close to synthesizing life, there is a need to bring together experts from different disciplines to work on the fundamental science and to address the historical background and ethical issues that may arise. The topic is of strategic relevance for Faculty of Natural Sciences at Aarhus University since it is a rapidly developing research topic with several big initiatives on "synthetic cells" being taken world-wide and since Aarhus University has a unique chance to establish a strong interdisciplinary research environment on this topic.
The bottom-up synthesis of life is a grand challenge that we still don't know the solution to. Several approaches have been proposed (Jia & Schwille, 2019; Rothschild et al., 2024; Kriebisch et al., 2025) that focuses on mimicking the fundamental properties of life such as: (1) replication and evolution, (2) compartments and division, (3) enzymes and metabolism, (4) molecular machines and regulation, and finally to integrate these elements in synthetic cells that come to life i.e. self-replicate and evolve. Below we describe these central properties of life and how they can be developed from scratch and possibly integrated.
Replication is the process by which molecules, particularly nucleic acids like DNA and RNA, make copies of themselves. Evolution refers to the change in species over time, driven by variations in their genetic material. These processes are fundamental to life, as it allows genetic information to be passed on from one generation to the next and to better adapt through natural selection. Research in artificial biology focuses on how to develop molecular replication and evolution with different building blocks capable of linking information (genotype) to function (phenotype) into synthetic life-like systems.
Compartments are crucial for life because they help organize and protect essential processes. In biological systems, compartments like cell membranes separate different environments, allowing distinct chemical reactions to occur in an orderly manner. Research in artificial biology aims at the assembly of artificial cells that mimic the functions and structures of natural cells using various materials, such as lipids, proteins, nucleic acids or alternative chemical structures. Grand challenges are to develop mechanisms for cell division and cell mobility. Cell division allows genetic inheritance and evolution of life-like systems and cell mobility allows the system to actively seek out food sources.
Enzymes and metabolism are essential for life because they enable the chemical reactions that sustain all living organisms. Enzymes act as catalysts, speeding up these reactions and allowing them to occur efficiently under mild conditions. Metabolism refers to the sum of all chemical processes in an organism, including breaking down nutrients for energy (catabolism) and building complex molecules for growth and repair (anabolism). Research on developing artificial enzymes and metabolism for synthetic cells is focused on creating custom-designed catalysts and metabolic pathways that can mimic the complex biochemical processes of natural cells.
Biological molecular motors are complex proteins powered by chemical energy to produce directional movement and carry out specific tasks. In living organisms, this motion is crucial for various complex and essential functions, such as transporting cargo, signaling, cell movement and division, and nucleic acid polymerization. Misfolding or mutations in these protein machines can lead to severe diseases or even be fatal. Our research goal is to construct artificial molecular motors that can replicate such complex functions, including dynamic and reciprocal molecular communication, and integrate them in life-like systems.
A major challenge is how to integrate the above-mentioned artificial life-like elements and make them work together in synthetic cells that becomes self-sustained and capable of Darwinian evolution. Our approach is to develop the different elements together and in a modular fashion with integration in mind. Central to creating a life-like system is to have replication at the core to allow it to evolve novel solutions. Developing novel life-like systems is of scientific and technological interest but also raises possible security and ethical questions, which we will address as well.
