Emerging Life Sciences Series: Q&A with the Editor: Artificial Biology – Assemble, Imitate, Adapt

Abstract

Städler: I became fascinated with the hierarchical structure of mammalian cells when writing my postdoc fellowship application back in 2007. At that point, encapsulated catalysis existed, but sub-compartmentalization was a very new concept. We invented capsosomes (liposomes as subunits in polymer multilayer capsules), a very simple artificial cell, especially when looking back. When I started my independent research group in Denmark, the question was never IF we will be working in the area of artificial biology, more WHICH of the many aspects, we will be focusing on. For me, the most fascinating questions were and remain around considerations of how to integrate a bottom-up assembled life-like unit with living mammalian cells.

Valero: I have always been fascinated by how biological systems work. For a chemist, a cell is a paradigm of complexity, where highly efficient reactions, molecular interactions, self-assembly, nanomechanics, directional transport, etc., harmoniously converge in a single entity. Inspired by Richard Feynman's quote: “What I cannot create, I do not understand,” my approach to biological systems involves developing artificial prototypes based on nucleic acid building blocks that mimic the structures and functions displayed in nature. These artificial molecules not only contribute to shedding light on how biological systems work, but they can also exhibit novel and enhanced functionalities that can be integrated to create unique synthetic biology systems or used for biomedical applications.

Zelikin: I am teaching medicinal chemistry and through this, I gained an understanding and appreciation of the molecular composition of a cell; it inspired me, and challenged me to pursue this elegance and complexity of composition via the bottom-up approach, using in-house made molecules.

Sanchez: There are a few reasons: I always loved the idea of reproducing the complexity of living systems by engineering something with our own hands, trying to mimic at least one of the hallmarks of life. For instance, in our lab, we focus on motion, from single to collective phenomena. And I still want to combine these artificial systems with living/biological components, such as cells or enzymes. That is what we call hybrid systems.

Sanchez: Definitely nanomedicine. With the combination of artificial and biological components, we can design better delivery vehicles that interact more efficiently with biological systems and biomaterials such as cells and tumors.

Valero: I believe integration and adaptation to living organisms are key for the advancement of the field. We need to develop artificial systems that do not merely work in parallel but rather integrate with cells, tissues, and organs, offering feedback communication and the capability of adapting to their environment and physicochemical signaling. An advanced feature of future synthetic biology systems will be to combine their adaptive properties with replication, allowing them to evolve together with the biological landscape where they are integrated.

The fields of prosthetics, genetics, and tissue engineering have largely benefited from artificial biology over the last decade. Current efforts on de novo protein design and its integration with artificial intelligence are opening new avenues for developing synthetic proteins displaying unprecedented molecular recognition and catalytic features. With the development of these advanced artificial systems, the next steps are focused on tackling more complex biological systems, with implications in the areas of immunology, gene regulation, and neurobiology.

Zelikin: In my personal opinion, artificial biology at this stage of development is a lot less “biology” than engineering. And I do not mean it in a negative way, not at all. But to advance further, I think it is critically important that “artificial biology” gets recognition by biologists. As one possible idea to achieve this, I propose that we focus less on making synthetic cells that mimic natural cells. Instead, we should make synthetic cells that do something that natural cells cannot do. Then a co-culture, an ensemble of natural and synthetic cells may have properties and functionality exceeding that of the all-natural ensemble.

Zelikin: I think our only barrier and limitation is our imagination. And then once we have created that “what is worth sharing” with biological systems, the challenge would be to achieve synergy between artificial biology and nature.

Sanchez: The development of fully biocompatible systems is a limitation. The complexity of some nanomotors found in literature seems too high from the regulatory point of view and for the scalability of future steps.

Städler: Since a widely explored idea is to assemble “life-like” units, questions involving what is life are important and interesting to discuss. Today, we probably do not do this sufficiently with scientists outside of natural science and engineering e.g., experts in bioethics, and religious science. Should concepts from artificial biology eventually be considered for clinical translation, the perception of patients will be important, and self-sustained or even self-replicating systems will raise ethical concerns.

Städler: My goal is to collect contributions from very different aspects of artificial biology in the same Special Issue to illustrate the interdisciplinary nature of this field. For me, the Special Issue will be successful if we manage to attract contributions from research groups from all over the world, from laboratories that have been successful for many years, and also from young group leaders who will shape the future of science.

Zelikin: We are trying to build a community, to recognize each other and build partnerships, and of course present this field of science as a maturing discipline that has a lot to contribute to the other disciplines. Our success will be to be recognized, to be cited, to be acknowledged.

Andersen: The goal is to inspire research in artificial biology by gathering researchers from various disciplines to share their recent work on this topic. Artificial biology is an ambitious and futuristic research field that aims to engineer life-like systems and develop novel technological solutions. The success of the current issue will be measured by its ability to attract interest to the field and inspire future research.

Sanchez: I would like to see a good number of contributions on how the field of nanomotors is advancing in biomedical applications. Additionally, it would be interesting to see manuscripts reporting at a fundamental level on the construction of new artificial systems with new functionalities, biocompatible materials, or new propulsion mechanisms.

Valero: My main expectation for this special issue is to bring together the latest contributions from the field, including works that have the potential to develop and transcend into other areas of research, while also influencing and inspiring other scientists. Ideally, the special issue will cover the most important trends and future directions of artificial biology, serving as common ground for taking the next steps in the field.

Affiliations

Professor Brigitte Städler, Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus, Denmark

Assistant Professor Julián Valero

Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus, Denmark

Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark

Professor Alexander N. Zelikin

Department of Chemistry, Aarhus University, Aarhus, Denmark

Associate Professor Ebbe Sloth Andersen

Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus, Denmark

Professor Samuel Sánchez Ordóñez

Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Barcelona, Spain

Institució Catalana de Recerca I Estudis Avançats (ICREA), Barcelona, Spain