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Building a Synthetic Cell

Marileen Dogterom

30 April 2016 - updated 4 years ago
21 comments
Total votes: 1

Document(s):

fetflagshipsconsultation2016syntheticcell.docx

Author(s):

Marileen Dogterom

Year of publication:

2016

Tags:

FET Flagships consultation

Building a synthetic cell is one of the grand scientific and intellectual challenges of the 21st century. While we now have extensive knowledge about the molecular building blocks that form the basis of modern life, we currently do not understand how these building blocks collectively operate to define life. Cellular life, which provides the fundament of most organisms, appears to be the result of a collection of highly controlled, energy consuming, dynamic self-assembly and self-organization processes that lead to autonomous entities that can reproduce, transfer information, interact, and evolve.

Building a synthetic cell is the most fundamental approach towards elucidating the cell’s intricate working and the basic life-defining principles. Truly understanding life will bring huge intellectual, scientific, and technological rewards. At the same time it will raise fascinating philosophical and ethical questions, as it impacts on our fundamental understanding of ‘who we are’.

Comments

Paolo De Los Rios,

01/11/2017 23:03

Building an artificial cell will be an incredible adventure. It can be compared to building a new house from scratch by people who are not knowledgable of concrete-science, of water, electricity and heating distribution systems (and likely not even fully knowledgable of any of their underlying disciplines), of thermal insulation and so on. As a matter of fact, these builders do not even know all the systems they will need to build the house and to make it function. But they will have to learn by trying. Fortunately, for every problem they will encounter, they will be able to look at the solutions that are already on the "market" (real, naturally evolved cells, in this case) and understand what they are neglecting and what they are making wrong. This will provide an unprecedented puropose in the way the cell is analysed.

As an exemple from my own research, it is now clear that cells survive thanks to the constant action of molecular machines that control the conformational state of proteins, RNAs and DNA (at the cose of energy), guaranteeing macromolecular homeostasis. Any synthetic cell will have to include some sort of similar quality control mechanism, because errors are unavoidable, due to stochastic fluctuations and by external stresses.

Looking back not more than 30 years ago, the presence and overarching relevance of these processes was not fully known and appreciated. Very likely, there are many other mechanisms and processes that are necessary for the life of the cell, that we have not yet recognised as such.

Our failures at building a synthetic cell, possibly more than our successes, will guide us at asking the correct questions when looking at real cells, learning, imitating, and ultimately being able to create cell-like organisms that we can use for research and, down the road, for controlled appplications.

Ulrich Schwarz,

23/03/2017 07:59

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.

Dennis Claessen,

06/02/2017 12:54

"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.

Dennis Claessen

Vassilis Papadakis,

22/12/2016 12:41

What an excellent project!

I would like to support this action from the bioimaging point of view.

Please consider my contribution to this initiative!

Brian Jester,

19/12/2016 12:31

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!

Jan-Willem Veening,

13/12/2016 11:27

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.

Sophie Martin,

12/12/2016 21:55

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.

Derek Stewart,

28/11/2016 15:30

Interested in this project but with the view point of employing plane and crop genes for new products also. What is the state of play with the proposal?

Cheers

derek

Andres de la Es...,

21/11/2016 19:13

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.

Daniel Riveline,

20/11/2016 09:25

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.

Erwin Frey,

19/11/2016 23:37

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.

Kirsten Jung,

02/11/2016 13:19

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).

Bert Poolman,

02/10/2016 16:55

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.

Philipp Holliger,

28/09/2016 13:14

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.

Hagan Bayley,

24/09/2016 12:15

I support this Flagship proposal. At the fundamental level, the proposed research will allow 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.

Gijsje Koenderink,

16/09/2016 09:10

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.

Wilhelm Huck,

15/09/2016 21:26

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.

Cees Dekker,

15/09/2016 19:21

What is life? How is life different from nonliving? What minimal elements are needed to constitute a living cell? How do the laws of nature give rise to biological self-organization? Can we build life from scratch? Questions like these have puzzled mankind for ages.

Despite a century of intense research, this question has not been answered. Indeed, it has remained a daunting puzzle how in the world first cells have arisen from molecular components. Excitingly, a new development has been emerging in the past few years: synthetic biology. Key to this field is the notion that biology has become an engineering discipline. Synthetic biology involves the rational design and synthesis of complex biology-based or bio-inspired systems that display useful functions, even ones that do not exist in nature. The leading motto of synthetic biology can be summarized by a quote of eminent physicist Richard Feynman who wrote ‘What I cannot create, I do not understand’. Indeed, it is often only by actually (reverse) engineering a system that we really grasp the full complexity of it and thus understand the underlying principles in depth.

This truly exciting flagship proposal addresses the ultimate challenge of bottom up synthetic biology, namely to construct a synthetic cell from basic molecular components, a cell-like object that can sustain itself by consuming energy and that can reproduce into similar offspring. For a very long time, assembly of even a minimal cell-like object was deemed to be impossible, but with the advance of synthetic biology, multiple groups worldwide are now starting projects towards this goal. The European community is exquisitely lined up to take a leadership role in such a challenging enterprise, as it has many of the leaders in the field – Marileen Dogterom clearly being one of them.

Engineering a living cell from basic components is one of the most challenging goals within the life sciences today. Assembly of a synthetic cell will profoundly deepen and propel our fundamental insights into the workings of a living cell. If accomplished, it likely will be ranked as a monumental achievement in science – yielding a string of Nobel Prizes as well as opening up entire new areas for applications from bioengineering to nanomedicine.

The challenges are immense because such an enterprise technically comprises many aspects such as the ability to sustain a synthetic cell with a stable metabolism that processes nutrients and supports all cellular activities, maintenance of an information-processing system that can replicate a genome and translate its information into proteins and other building blocks, as well as engineering a minimal machinery to provide growth and division of a synthetic cell into offspring. A rational way to tackle this enormously complex challenge is a reductionist approach that divides the problem into tractable basic units, studies each one separately, and finally combines them again. Indeed, the flagship proposal sketches some concrete promising directions to address the challenges. Clearly the recent scientific developments in the field make it opportune to now embark on a flagship-scale effort to build synthetic cells.

Next to truly profound scientific insights, it can be expected that a flagship on synthetic cells can be expected to have deep impact beyond the scientific discoveries. I expect that it will open up complete new application areas in the areas of medicine, biomaterials, food and bioengineering in general. This could give Europe a leading edge in these developments.

Dieter Braun,

12/09/2016 14:05

What is more fundamental to science than to understand how dead molecules can be lifted to a living entity? The progress in biology, biophysics and biochemistry should be put to a test by trying to recreate life. Only what you can create you really understand. The progress in understanding evolution and the stability of living entities will be tremendous and feeds into completely new viewpoints for medicine, biotechnology and the life sciences. The technology is here and the challenge will focus the expertise to match bottom up methods with top down biology.

Petra Schwille,

12/09/2016 13:15

This is without doubt one of the most fundamental and generally interesting topics of research for both, the quantitative, and the biomedical sciences. The phenomenon of life, which is always found to be cellular, has been riddling humans for ages, and in spite of our enormous progress in understanding its details, we are still far from understanding its origins, and whether and how exactly it distinguishes itself from non-living matter. Armed with cutting-edge technology and methodology from the different "connecting" disciplines physics, chemistry, and molecular biology, the time has come to re-address the question whether life could be reconstructed in the test tube, and what its necessary requirements and constituents would be. Europe has a large number of eminent researchers addressing these questions from various countries and disciplines, and could even take the world leadership if making a concerted effort for this basic a grand research initiative in the near future.

Joachim Spatz,

12/09/2016 12:46

Flagship initiative for “Building a Synthetic Cell”

I am writing this note in full support of the initiative by Professor Marileen Dogterom for a couple of reasons as stated below.

These days, national initiatives for “synthetic cells” are appearing globally. However, the field is so rich and diverse that a coordination between these national activities would greatly support the successful development of synthetic cells. This is a truly interdisciplinary subject which not only involves natural scientists but also social sciences for ethical reasons. Indeed, this project has far reaching implications extending beyond biochemistry, molecular biology and physics and into philosophy and bioethics.

The past fifty years of biological research have gleaned a tremendous amount of knowledge on the basic components of cells (ions, carbohydrates, proteins, etc.) including most of their structural information, but an understanding of how these components come together to yield sustained function, division, and life remains elusive. Up to today, the pure molecular biology approach towards knocking down/out specific molecular players in a natural cell, i.e. top-down molecular biology approach, only gained a few additional information and often failed due to the tremendous complexity given in living cells. In the next fifty years, the inevitable construction of a functioning synthetic cell by a bottom-up or self-assembly approach will be a Nobel-prize worthy discovery, one that will rewrite science texts and open a new frontier of biological-medical possibilities.

This initiaitve comes at an ideal time in the field, as CRISPR-Cas9 genome editing systems are reaching widespread adoption, microfluidic techniques required for droplet compartmentalization are being perfected, and great strides have been made in quantitative understanding of complex biological systems and processes.

This initiative is a quintessential example of the type of research that the Flagship program was founded to support. The initiative is highly challenging and provides a clear perspective that will lead to innovative insights and breakthroughs of international stature. The results will be clearly visible at an international level and it will belong to the world top. Such an initiative will clearly incorporates most of the best researchers in Europe, from several disciplines, to facilitate research excellence. This makes this initiative ambitious, high-impact, and extremely necessary, and will yield important results that have the potential to change the field.

The coordinating researcher, Professor Marileen Dogterom of the Delft University of Technology, has an extensive publication record and is globally well known for her pioneering research into cytoskeleton / molecular motor (microtubule / kinesin dynamics) which are truly educational for the in vitro life scientist. As this initiative will also revolve around reconstituting elements of the cytoskeleton in synthetic cells, her expertise in several cytoskeletal components as well as synthetic mitotic spindle in vitro reconstitution is invaluable to the success of the initiative. On top of this profound scientific base she must be an excellent leader which is represented by the different tasks and positions she covered in her career. E.g. she is honored by different national and international prices, e.g. an ERC Synergy Grant (lead by Dogterom), an ERC Advanced Grant and highest national and international scientific prices.

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