Fantastic and timely initiative!

Artificial enzymes, synthetic receptors

A flagship focused on the challenge of building a synthetic cell would be key to answer some of the most fundamental questions that current biology, and also chemistry, have in their horizon: what is life; how did it originate, on Earth or elsewhere in the universe; and how we can implement artificial life-like systems with novel properties and functions. By creating a synthetic cell from the most basic biological components, or even from artificial ones, we will acquire a much deeper understanding of life and the (bio)molecular networks that sustain it. Moreover, although it is difficult to anticipate how accomplishing this challenge will impact into the market of real applications, there are plenty of technological possibilities that could emerge from this approach, whcih certainly justifies the establishment of a flagship around this topic.

Synthetic cells will be key for future developments in exploiting cells for the production of pharmaceuticals, nutrients and soforth. They will allow us to extend beyond the current possibilities that biology gives us and include non-canonical buildings block as well as help us to understand the complexity of live, and possibky even the origin of life

One of the most exciting activities in contemporary life sciences. It will teach us a lot about how life functions at the molecular level. I am very happy to support this initiative and contribute to the research, where possible!

Now is the time for a synthetic cell flagship Complex networks of proteins, nucleic acids and small molecules sustain the essential processes of energy provision, gene expression and cell division that characterize living cells. Over the past decades, many of the molecules that make up cells have been identified and studied. Yet, despite increased chemical and physical understanding of these biomolecules and their mutual interactions, it remains elusive how they together form a cell that can autonomously grow and replicate. While we are not yet capable to construct such functional biological systems de novo, we can start to assemble and analyze minimal systems that mimic cellular behavior, with the ultimate goal to engineer a synthetic cell. I very much like the idea of constructing a minimal form of life; it is extremely challenging and requires the expertise of scientists from several disciplines but now is the time to bring the right people together. The proposal of Dogterom addresses a problem where Europe can make a difference. It requires long-term funding and a clear vision on which problems to tackle (how, when, where), and a strategy to effectively collaborate across various disciplines of the life, natural and computational sciences and the humanities; the topic will bring ethical and philosophical issues on “what is life”. The construction of a synthetic cell will give unprecedented insight in the “laws of life”, and, ultimately, it will allow us to engineer different forms of life to address the Grand Challenges of Europe.

This is an excellent project. The economic impact of the work will be huge. This program would lay the foundation for Europe to lead the world in Synthetic Biology. To begin to imagine that we will eventually be able to custom build organisms, tailor-made for specific functions is extremely exciting. The applications of the new technologies will expidite the transformation of Europe into a sustainable bio-economy. Many sectors of society will benefit from the work, from production of commodities to new biofuels, and bioremediation as well as new solutions that address the increasing global demand for food. The work will involve interdisciplinary teams and approaches. Academically, we will begin to have answers for some of the most fundamental questions that mankind has ever asked. What constitutes life... I highly endorse this project!

My group studies actin dynamics in adhesion by combining fluorescence spectroscopy and microscopy with in vitro reconstitutions. We are currently reconstituting a synthetic focal adhesion. In parrallel to my research at CNRS, I am Professor at Ecole Polytechnique and Chairman of the Physics and Biological Systems conference in 2020

Building a synthetic cell is a central goal in the research community at the International level, from Physics and Biology to Chemistry and Maths. I support this initiative for the following reasons : - Central discoveries performed in Europe or by scientists with a European education : these topics have been flourishing in the last decades, in particular with pioneering works in Europe, in France, in the UK, in Germany in particular. Scientists re-visited basic principles of auto-organisations in chemistry/physics, and they were asking differently questions beyond molecular reactions through their visions in terms of networks, mesoscopic scales, new theory for living matter, out-of-equilibrium physics. New ideas for spatial organisations of active matter or for signal processing in signaling networks have paved the way towards new Sciences in Biology and in Physics. The future of this field which had its founding works in Europe shoud be re-invested within Europe. - Novel education programs : these subjects require intense training in interdisciplinary fields as well as a general culture in Science, and several countries in Europe have launched such initiatives (for example at Strasbourg University : http://www.cellphysics-master.com/). New students will enter soon laboratories throughout Europe, and their creativity and ideas - which result from long term training and investment from European States - should be supported by Europe to trigger and probe new ways of viewing and understanding the living matter. - New sources for jobs and patents applications : this new way of addressing questions in the Life Sciences has started to generate new activities with unprecedented scopes. Microfabrication/Microfluidics or the design of Systems Biology approaches open the perspective of new ideas in organ-on-a-chip, and original strategies in drug designs and diagnosis. Europe could be the central player of these new fields with the associate consequences for generating new jobs and income. This new initiative could revolutionarize our ways of understanding cells, organisms, and living matter, and I think that Europe should have a leading role in this endeavor.

"What I cannot create, I do not understand", is the famous quote from the physicist Richard Feynman. Building a living cell is clearly one of the most difficult, yet important challenges that lies ahead of us. This exciting Flagship proposal tackles this challenge and will provide a major leap forward in our understanding of what defines life. I fully support this project and its multidisciplinary approach, which will provide Europe with a competitive lead in the fields of synthetic biology and biotechnology.

I like to fully support this great initiative; it addresses one of the most - if not the most - intriguing scientific question of today.

To understand the fundamental principles of life it is necessary to study living systems bottom-up. Building a synthetic cell will be a key step in this direction and will undoubtedly have a great impact on science and society as well. A quote from the theoretical physicist Richard Feynman "What I cannot create, I do not understand" sums it all up. From my perspective as a theoretical physicist a truly quantitative approach towards understanding living systems will require that we are able to build such systems and at the same time develop novel theoretical concepts and paradigms. The flagship would enable us to reach this goal and fundamentally change the way we view living systems.

I write in strong support of this flagship proposal. This proposal addresses the most central and exciting question that we can ask about nature: "what is life?", or in other words: "how does a collection of nonliving molecules together generate a living cell?". The premise is that we can only truly understand life if we can recreate it from its component parts. Now is a perfect time to launch such an ambitious programme, because advances in the life sciences and in physics have converged on a detailed understanding of the component parts of life while chemistry has at the same time come to a point where (supra)molecular systems can be synthesized that are able to mimic key functions of biomolecules such as self-recognition and mechanochemical activity. This flagship proposal presents a unique opportunity to bring life sciences, physics and chemistry together and put Europe at the international forefront of synthetic biology. In addition to providing revolutionary new insights into the origins of life, building a synthetic cell would also open a multitude of applications. Synthetic cells can be used as factories for bioactive compounds, as test beds in drug development, and as building blocks for materials with life-like properties such as stimuli-response, adaptibility, and self-repair.

At the fundamental level, the proposed research allows us to understand what we mean by alive or dead, and explore the fascinating territory between these two states. From the practical viewpoint, research in this area will lead to synthetic cells and tissues that can be used in medical applications. These materials will be safe and inexpensive.

We will gain incredible new biological insights by attempting to build a living cell from scratch. To accomplish this, we will need biologists, engineers, chemists and physicists to work together. From a molecular geneticist point of view, this is an extremely exciting project as it will provide us with the exact function of each essential gene, something that is unprecedented. For instance, in the project of Craig Venter, a minimal bacterial cell was constructed but the functions of 149 genes remain a complete mystery (Hutchinson et al., 2016 Science). The flagship project "Building a Synthetic Cell" will not only provide us clues into the origins of life, designer cells might become a real-world possibility allowing us to precisely produce novel or otherwise hard to obtain pharmaceuticals and enzymes. It can even be envisaged that such cells can be programmed to address other grant challenges such as water pollution, food supplements, vaccines, etc. In total, I fully support this Flagship and believe it is a unique opportunity for the excellent researchers in Europe that work at the interface of synthetic biology, cell biology and genetics to come together.

Happy to help if there are useful ways I can do so!

Expertise: Polymer microgels as cell-like reaction platform

This initiative dovetails very well with the COST project I chair, chemobrionics - see http://www.chemobrionics.eu/about - which is very much intertwined with the origin of life - see https://royalsocietypublishing.org/toc/rsfs/2019/9/6

I am coordinator of the graduate school "Molecular Principles of Synthetic Biology", and I am fascinated by elucidating the design principles of life. Therefore, I strongly support this initiative. My group is interested in bacterial stress response and translational regulation. We are investigating various receptors and transporters embedded in proteoliposomes. We are studying translational control by incorporating unnatural amino acids into elongation factor P, a conserved protein of all kingdoms. These studies are complemented by the discovery of new posttranslation modification pathways (e.g. rhamnosylation). Last but not least, we are working with outer membrane vesicles as signaling vehicles and VBNC state cells (viable but nonculturable cells).

As Feynman said: "What I cannot create, I do not understand"

Many of the greatest scientific achievements have been sparked by fundamental research. This initiative is probably as fundamental as research in the life sciences can possibly be - it concerns the very transition from chemistry into biology. And still its implications reach far into biomedicine.

Four billion years of evolution has yielded a biosphere packed with exquisitely optimised molecular components that enable life to evolve and thrive. Yet all of these components and systems are representatives of the last universal common ancestor (LUCA), a breakthrough organism that came to replace all alternative biologies. In the absence of the discovery of other biologies (on earth or beyond), it is impossible to establish universal principles and laws of biology. To paraphrase Carl Sagan, our biology, although amazingly diverse, is ‘provincial’, in contrast for example to the laws of physics, whose generality can be observed throughout the cosmos. I strongly support this Flagship Proposal for its ambition to go beyond the simple analysis and deconstruction of extant life and building ‘new biologies’ through modification, reconstruction and de novo construction and its promise of a fresh perspective and ultimately a better understanding of the unifying principles of living systems. The bottom-up construction of a synthetic cell with life-like properties like growth, heredity, division and evolution is in many ways the "moon shot" of synthetic biology. Comparable in ambition to the first genome sequencing projects, it will require input from chemistry, biology and physics and interdisciplinary collaboration across a wide range of disciplines. It will both stretch existing technology to the limit as well as create new ones including synthetic cells and tissues for uses in biotechnolgy and medicine. Finally, this new quasi-biological technology will provide fundamental insights into the inner workings of cells (and their origins) as well as present a foundational blueprint for the creation of evolvable nanostructures.

One of the grand challenges of this century will be to design and build a minimal cell that can self-replicate, i.e. grow and divide autonomously. This will not only drastically enhance our fundamental understanding of how life works at the cellular scale, but also be of tremendous importance for medicine and health. Due to recent advances in micro-fluids technology, imaging, and theoretical modeling, we can now successfully reconstitute individual modules, for, e.g., energy uptake, timekeeping and cell division. The field has thus reached the stage that we can aim for the next frontier, which is to combine these modules to create a minimal cell.

There are many ways to study life, and one that is particularly appealing is regarding it as self-organized active soft matter that is away from equilibrium ``just the right way’’. This proposal is of utmost fundamental importance as it provides a perfect complementary environment in which this notion can be explored and developed. A natural starting point will be to think about how we can begin to put together simple building blocks - from basic ingredients that we fully understand - that would exhibit the kind of active behaviour we find in living systems. A next important question to address is the stability of a living system made of active components, when the nonequilibrium processes that characterize life such as motility, chemical signalling, and cell division are present. The complementary studies of these different aspects, which can be harboured in such an all-encompassing European flagship initiative, can help create all the elements that are required for making living matter from the bottom-up. This initiative has my full and enthusiastic support, and I'd like to congratulate Professor Marileen Dogterom for taking the leadership of this important campaign.

I find this project extremely exciting and would like to express my strong support. I believe that scientists are now in the position to combine their individual expertise in a joint effort in order to reach goals that have seemed unrealistic year ago. I can only congratulate the "promoters" for starting the initiative!

Understanding what defines Life is without doubt one of the greatest scientific challenges of our time. The flagship project "Building a Synthetic Cell" addresses a true frontier of knowledge. By creating a living cell from individual components, this project aims for the first time to breach the divide between molecules and life, and thus help define the true nature of life. By its groundbreaking nature, this project will place European Science at the forefront of this important field. It will bring together scientists from various disciplines, foster technological developments, focus the ethical discussion and breach conversation with policy makers.

This is an exciting proposal and I would like to express my full support of it. The time is ripe to finally address the challenge of creating life-like features from bottom-up. If successful, this would not only be a huge intellectual achievement, but also would open up the door to a large range of very interesting and useful applications. I am convinced that this can be achieved by bringing together the recent advances in soft matter physics, biophysics, cell biology, systems biology and synthetic biology in a Europe-wide effort. A flagship format would be ideal for such a project. As a theoretical biophysicist, I would also like to emphasize that recently our theoretical understanding of structure formation and dynamical processes has profited a lot from inspiration by (synthetic) biology, and that in reverse, theory and simulation now could contribute strongly to such an endeavor.

What an excellent project! I would like to support this action from the bioimaging point of view. Please consider my contribution to this initiative!

How do molecules create life? Understanding the molecular mechanisms of life is the greatest challenge in the molecular sciences. The construction of a synthetic cell is the best approach to really uncover life's secrets. In recent decades, syntehtic biology has made tremendous progress in engineering living systems and creating minimal cells. However, only the bottom up construction of life requires us to address the fundamental challenge of understanding life. There is no blueprint to construct a living entity that can extract energy and nutrients from its environment to sustain itself, grow, and divide. Constructing a cell from its building blocks would be a monumental achievement and the fundamental breakthroughs in chemistry, physics and biology that will undoubtedly result from this effort will change the fields of physical and biological sciences forever. The magnitude of the challenge is tremendous, but European researchers are ready to take a global lead in the concerted, multinational effort across the physical and biological sciences that is required to build a synthetic cell.