• COST Action CM1304 - Emergence and Evolution of Complex Chemical Systems is a network comprising more than 90 European research groups. It has sparked invaluable collaborations that have helped advance the emerging field of systems

Systems Chemistry The next big frontier Sijbren Otto introduces us to systems chemistry, explaining why this field is so important and highlighting the role of his work on the emergence and evolution of chemical systems in addressing some of society’s major scientific challenges

Could you briefly simply too difficult to study mixtures of It is still early days in the field and predicting introduce the . However, with the recent rapid concrete applications is notoriously field of systems development in analytical equipment this difficult. Yet I am convinced that, given the chemistry? situation has now changed. Also, mixtures of fundamentally new approach to chemistry, molecules have become tractable, opening such applications will emerge. The most The field of systems up the new discipline of systems chemistry. likely will be in the interface with life. As chemistry deals a significant part of systems chemistry is with complex chemical systems that show Can you discuss the advantages and about making chemical systems that operate properties that go beyond the sum of its disadvantages of employing a bottom-up based on the organisational principles of components. Such emergent properties are approach within systems chemistry research? living systems, their interfacing with living commonly found in systems that have many systems is likely to be more efficient than the components that interact with each other. For The bottom-up strategy is second nature to rather blunt approach taken in, for example, example, the dynamics and characteristics of chemists, who are used to building bigger pharmaceutics, that relies on drugs with a a society come about from the interactions systems from smaller components. In single active component. But even now, while between many different people. The field of synthetic chemistry the approach is already much groundwork still needs to be done, we systems chemistry is currently occupied with to join atoms into molecules and smaller are already seeing systems emerging that learning the rules that will enable the design molecules into larger ones. Thus, chemists come close to having applications. Examples of chemical systems with specific properties will take a bottom-up approach almost from our Action include the development of in the near future. It represents the next big without thinking. Top-down construction self-synthesising hydrogels for tissue-culture frontier in the chemical sciences. of complex chemical systems is of course applications and the assembly of organic also possible, as evident from the field of molecules into structures that conduct When compared to certain other disciplines, synthetic biology, where the approach is to electricity with an efficiency similar to metals. why is complexity science relatively take existing biology and modify it to suit new underdeveloped in chemistry? purposes. However, the bottom-up Systems Speaking more broadly, systems chemistry Chemistry approach is the only one that will is the area of science that is best placed The reason for this is mostly practical. allow completely new systems to be built and to address two of the grand scientific The components of chemical systems the only approach that may illuminate the challenges: the origin of life and the de novo (molecules) are much smaller than the origin of life and that would allow for the de synthesis of life. Addressing these will have components studied in sociology (humans), novo synthesis of life. huge implications for science and for society. biology (organisms) and most of physics. Due to their small size, molecules are much What are some of the potential applications harder to study. For most of the history of that may emerge from your COST Action chemistry, the focus has been on studying CM1304 (Emergence and Evolution of pure substances. Until very recently, it was Complex Chemical Systems)?

www.impact.pub 57 A new paradigm COST Action CM1304 - Emergence and Evolution of Complex Chemical Systems is developing far-from-equilibrium self-assembly and self-replicating systems, self-assembling and reproducing compartments, and the use of information-rich molecules in these contexts

Systems chemistry is a rather young field to shaping the community.’ now switching from the development of the that has so far had little attention dedicated theory to real-world applications.’ to it. However, with complexity becoming Collaboration is crucial to shedding light on The Action brings together more than 90 increasingly important in chemistry, the field systems chemistry, as Pascal highlights. ‘The European research groups focusing on is extremely vital. Researchers in this topic establishment of a community of scientists systems chemistry and is divided into four have long recognised this, and one COST through three different COST actions over WGs. Jan van Esch is coordinating WG1 Action in particular is striving to establish a time span of 15 years has been highly which is establishing the methodology for Europe as a world leader in this area. beneficial to the development of this field of self-assembly far from equilibrium, which science,’ he states. ‘This has not only been requires the supramolecular and far-from- COST Action CM1304, ‘Emergence and made possible through the realisation of equilibrium communities collaborating. Evolution of Complex Chemical Systems’, collaborative investigations (through short- WG2, coordinated by Nicolas Giuseppone, has brought together a vibrant and coherent term scientific missions, for instance) but is developing a new class of materials research community in the field of systems also because it has allowed the distribution that are self-synthesising, responsive and chemistry in Europe that is connected of concepts in the community and favoured potentially self-repairing, which will involve through the COST network. Professor Otto their acceptance as new paradigms for the combining the autocatalytic systems explored Sijbren, from the University of , foundation of a new field of science.’ by the origin-of-life community with the , is Chair of the Action and self-assembly principles of supramolecular works alongside Vice Chair Professor A WORLD LEADER chemistry. This group is also developing Gonen Ashkenasy, Science Officer Dr In order to establish Europe as a world leader synthetic self-replicating systems capable of Lucia Forzi and a number of key partners in the emerging area of systems chemistry, undergoing Darwinian evolution, requiring including Jan van Esch, Nicolas this Action is bringing together communities input from researchers from the origin-of-life Giuseppone, Peter Walde and Robert Pascal working on supramolecular chemistry, far- and the far-from-equilibrium communities. as working group leaders and Drs Annette from-equilibrium systems and the origin of Taylor and Kepa Ruiz-Mirazo in charge of life. The key goals are to develop far-from- WG3, coordinated by Peter Walde, focuses dissemination and scientific exchanges, equilibrium self-assembly and self-replicating on developing methodology for the respectively. systems, self-assembling and reproducing compartmentalisation of chemical systems compartments, and the use of information- to achieve a direct coupling between Their four year programme of work began in rich molecules, which the researchers are chemical reactions, energy harvesting and December 2013 and is the third in a series aware necessitates a multidisciplinary transport and membrane dynamic, while of Actions. ‘The first Action on prebiotic approach. ‘The term ‘complexity’ is typically WG4, coordinated by Robert Pascal, looks chemistry and early evolution was initiated used to describe situations where the at developing synthetic, information-rich by Pier Luigi Luisi, followed by an Action on behaviour of the whole (system) cannot molecules or assemblies that have the Systems Chemistry, initiated by Günter von be predicted from the individual parts. potential of being replicated in a purely Kiedrowski,’ explains Sijbren. ‘Through these This area of research crosses traditional chemical system. Actions considerable momentum on systems discipline boundaries and new centres of chemistry had already gathered, yet much excellence have emerged across Europe CHALLENGES AND SUCCESSES work still remained to be done, both with bringing together researchers from diverse Challenges faced by this Action have involved respect to developing the science as well as backgrounds,’ explains Taylor. ‘The focus is the integration of different fields, which is

58 www.impact.pub an ongoing challenge for systems chemistry. However, the network has seen success in doing so. ‘The grand future challenge will be to connect the area of systems chemistry to biology, physics and social sciences to get a full perspective on complexity and emerging behaviour. It is evident though that this first requires a solid aggregation of chemists around the theme of systems chemistry,’ Prins says. ‘The COST CM1304 has been very successful in doing that by assembling a large group of scientists with entirely different backgrounds but with a common interest in systems chemistry. Considering the intrinsic multiple facets of this emerging research area it is of fundamental importance to connect the various sub-disciplines in order to advance the field. Clearly this poses also a formidable challenge as the different Self-organisation in peptide systems can be brought about by feeding the system with activating agents as cyanamide

members of the Action.’ COST has led to the basis for an EU-wide approach to The Action has seen great success in work on complex chemical systems, and started training a sparking discussion and collaboration, making significant strides in furthering new generation of students in this exciting field progress in the field. As a continuation on a series of Actions, Action CM1304 has seen positive outcomes in continuing communities may have different languages, field,’ enthuses Hermans. It has succeeded momentum and shedding greater light on perspectives, and ambitions.’ in bringing together communities that, at the systems chemistry through the impressive In order to overcome this challenge, the beginning only had very weak links. establishment of a community. ‘Outside Action organised meetings for the working Europe several researchers are also highly groups, with a view to sparking cross- DISSEMINATION AND PROGESS interested in the topic of Systems Chemistry, disciplinary discussions and initiating The project results have largely been but no community has yet emerged from collaborations. ‘Altogether this meant that disseminated through annual conferences, these efforts. Thus, I would characterise the towards the end of the Action virtually all which involve external invited speakers and status of the field outside Europe as more people that actively participated knew each WG meetings. ‘Members of our Action also fragmented and less coherent than within other,’ states Sijbren. took part in other European meetings, for Europe, where the consecutive COST Actions example there was a session co-organised by have contributed strongly to forging cohesion A number of successes have emerged, to date, us at WIVACE: the 10th Italian Workshop on between researchers studying the various including the formation of a new network on Artificial Life and Evolutionary Computing,’ aspects of the field,’ Sijbren concludes. Not chemical reaction cycles in the form of an says Taylor. ‘Selected papers from the only has the Action help shaped the research Innovative Training Network (ITN) with other session on Biomimetic Compartmentalized community on systems chemistry in Europe, COST members. ‘COST has led to the basis Chemical Systems were published as part it has also increased awareness beyond for an EU-wide approach to work on complex of the Springer series Communications in Europe. chemical systems, and started training a Computer and Information Science and new generation of students in this exciting involved collaborations with numerous

www.impact.pub 59 A vibrant research community Key partners involved in COST Action CM1304 – Thomas Hermans, Annette Taylor, Robert Pascal, Leonard Prins, Addy Pross, Tom de Greef and Ryszard Ostaszewski – provide an insight into the project that is helping establish Europe as a world-leader in the emerging area of systems chemistry

molecules’. This WG has been present though of scientific group at Institute of Organic several interactions with members of other Chemistry Polish Academy of Sciences my WGs. For instance, and from a scientific point responsibilities involves grant funding for of view, my research group in Montpellier scientific activity. Based on discussions with working on the systems chemistry of amino COST action members a grant proposal was acids and peptides has also worked on the prepared and submitted common chemistry of these chemicals with to the National Science Center Poland. Our nucleotides (in collaboration with John grant proposal entitled ‘Intensification of Sutherland, Cambridge) and membrane- multicomponent and cascade reactions by forming fatty acids (in collaboration with Kepa liposome and biocatalytic methodologies’ Ruiz-Mirazo, San Sebastian) taking advantage was positively evaluated by the National of the European network of CM1304. Another Science Center Poland. The grant started in collaboration with Addy Pross was devoted June 2015 and gave me resources to conduct to understanding the physicochemical experimental work and hire PhD students. underpinnings of biological evolution and the Two PhD students are involved on this project requirements for an evolutionary process to together with two senior scientists. During the be initiated. COST Action I participated in conferences and events organised presenting our results. In LP: I participate in WG3, which is March 2017 I was in charge as a chairman of dedicated to studying the importance WG3 COST meeting entitled ‘The influence of of compartmentalisation for controlling Vesicles Membranes on Chemical Reactions’. chemical reactions, evolution, transport, This meeting was organised in Warsaw Clockwise from top left: etc. The reason for me to join this working bringing together 21 scientists. During this Thomas Hermans, group was our recent entrance in the world meeting I gave the lecture titled ‘Investigation Annette Taylor, Robert of the Ugi reaction in an aqueous vesicle Pascal, Leonard Prins, of liposomes. The COST network provides Addy Pross, Tom de Greef an excellent framework for connecting to system’ and my coworker, my PhD student and Ryszard Ostaszewski researchers with a large variety of expertise Daniel Paprocki, gave a talk called ‘Self- and backgrounds and this permits rapid promotion of a multicomponent reaction in What are your respective roles and familiarisation with the techniques and aqueous medium’. responsibilities in the COST CM1304 project? protocols of a new research area. Can you highlight any successes you have AT: I was a member of the management AP: My role was as a researcher on the seen through the COST CM1304 project so committee, a member of working group theoretical aspects of the origin of life. Much far? (WG) 1 and responsible for the Action’s of the work I carried out during the Action was dissemination activities. I also hosted a in collaboration with Professor Robert Pascal. TG: The workshops and conferences were number of Short Term Scientific Missions characterised by many informal discussions. (STMS) for younger researchers. RO: At the moment I am member of WG4 and Because many Principal Investigators associated with WG3. Initially my scientific presented work that was not yet published, RP: I have been involved in the CM1304 action background was closely related to WG4 it provided an ideal opportunity to discuss, as a member of the management committee activity although some relation to WG3 was for example, critical control experiments and as a leader of WG4 on ‘Information-rich built up during the COST action. As a leader or new directions. In many cases, I have

60 www.impact.pub seen that these suggestions actually ended chemistry community, which is promising for AP: Like beauty, challenges are in the eye of up in published papers, meaning that the the future of both domains. the beholder. In my view, the central challenge interactions at the COST meetings were vital in origins of life research would be to in shaping the content of the paper. Have you faced any challenges in the COST generate a replicative system in the Dynamic CM1304 project? Kinetically Stable (DKS) state. In recent years, TH: Our group has benefited from COST in researchers in our Action have been able to the interaction with fellow scientists. We have AT: This COST action brought together generate non-replicative DKS systems and started to collaborate with several people over 90 researchers from 22 countries with discovered their remarkably distinct properties in the network, especially on the theory expertise in the fields of supramolecular compared to regular chemical systems, of complex chemical systems. We have chemistry, the origin of life and far-from- in particular their special self-assembly extensive experience in making and studying equilibrium systems. One of our aims was characteristics. The fact that such systems complex supramolecular systems, but when to develop complex chemical systems with are kinetically tunable means that their self- it comes to modelling them mathematically, new properties and functions. However, the assembly is dynamic and can be modified we often need a bit of help. So, as a scientific members had very different approaches and readily. Living systems indeed utilise such success I would say that bringing together communication between theoreticians and systems routinely. One striking example is the people from diverse fields and combining experimentalists was still limited. One of the cell cytoskeleton whose dynamic character both experimentalists and theoreticians has big challenges for systems chemistry is that controls cell form, governs material transport been very valuable. in dealing with complex chemical systems, a and cell division. Once a replicative DKS language has to be developed that is common system is generated, then theory predicts it RP: Certainly one success is the work to all and data interpretation requires a will likely seek to evolve toward more complex, of the group of John Sutherland who different approach than chemists tend to more DKS stable forms. An evolutionary has recently demonstrated how simple employ. In order to tackle these issues, we process toward complexity and life would have chemical and photochemical processes held two training schools led by theoreticians been initiated. Such an achievement would starting from hydrogen cyanide, a simple but open to experimentalists across the be no less than spectacular, and would, in my made of three atoms only, can Action. This gave us a unique opportunity for view, go a significant way toward resolving the lead to an impressive range of biomolecules hands-on training of the next generation of OOL problem, at least with respect to its more representing the majority of the building researchers working in a chemistry laboratory tractable historic aspects. blocks needed for to develop. but able to deal with the language of I also think the developments made in the complexity. We had participants from different Why is it important to establish Europe as a field of out of equilibrium self-assembly (Jan backgrounds and from all over Europe. world-leader in the emerging area of complex van Esch from Delft and Leonard Prins from chemical systems? Padova, for instance) and the fact that this More generally, what are some of the current action has integrated the field of the study of challenges in experimental research on the AT: Although the idea of harnessing far-from-equilibrium systems to the systems origin of life? complexity in chemical systems has been around for some time, systems chemistry has evolved less rapidly than its biological counterpart; systems biology. Many of the researchers in this Action were inspired by the goal of the creation of life from synthetic components. Taking inspiration from nature will allow us to design functional materials and processes that are greener or more sustainable, but also harness the unique properties arising from complexity in natural systems. The continued exploration of a systems approach to chemistry has the potential to dramatically change how we do chemistry in the future.

LP: I see systems chemistry as the third wave in the development of chemistry as a science. After having mastered the covalent

www.impact.pub 61 bond and the noncovalent interactions present their results and discuss particular TH: I think getting people excited by science between molecules, systems chemistry aims issues with the best experts. Face-to-face can be done in a variety of ways, but recently at understanding the properties that emerge contacts allowed us to know each other there has been a surge in dissemination from the collective behaviour of populations of better and provide additional stimulations through social media. A number of Facebook molecules. Systems chemistry offers a bottom- to conduct research at the highest level. pages translate scientific findings into small up approach to complexity as opposed to the Still in Europe the scientific activity in less movies or animations that are easy to follow. top-down approach used by biologists. This favored countries suffered from a lack of Sometimes the latter translation is not on will allow us to understand the chemical origin knowledge. Education also plays a very point and they often oversell the scientific of evolution, adaptation, signal processing, important role. During the COST Action findings, but it does often get the main motion, and other processes that are relevant scientists can motivate each other to change ideas across. Such animations are, however, to life. This knowledge will allow us to it and initiate international projects which quite pricy, and therefore not available to all implement these in new materials, medicine, are based on personal contacts. This cannot scientists. It would be a great idea to include catalysts, diagnostic systems and so forth and be achieved during common scientific some budget in EU projects for this specific there is no doubt that such smart systems conferences and meetings since those events purpose, or to set up a European animation will have unprecedented properties. Being are dedicated to other targets. Information studio to aid in dissemination to the general the leader in this field, Europe will be the also plays important role in scientific life. It public. One recent idea I really liked comes first to draw the benefits from this scientific is very difficult to properly select information from the Netherlands where they started the advancement not only on the societal level, for particular problems. Bringing experts ‘University of the Netherlands’. It is basically but also economically. together may help and facilitate information an open online portal where the best university teachers explain their science in simple words, and place their work in context bringing together people from diverse fields of the society. It makes fundamental science accessible to the general public, and is a and combining both experimentalists and great tool for communication. theoreticians has been very valuable Project Insights

FUNDING From your perspective what are the positive exchange and give a hint how efficiently COST is supported by the conduct scientific studies and combine the effects COST action meetings may have for EU Framework Programme the promotion of scientific collaborations results obtained from different laboratories. Horizon 2020 within Europe? This benefit is hardly achievable in many laboratories due to insufficient resources. PARTICIPANT COUNTRIES RO: Cost action meetings have a strong Austria • Belgium • Croatia • Czech influence on my research activity and How do you think we can better Republic • Denmark • France • Germany • Greece • Hungary • Israel • Italy • promotion of scientific collaboration within communicate outcomes and impacts from Netherlands • Norway • Poland • Portugal Europe thanks to a number of phenomena. technical science subjects to the wider public • Serbia • Slovenia • Spain • Sweden • The scientists from different countries can across Europe? Switzerland • Turkey •

CONTACT Some key publications from the Action: Professor Sijbren Otto 1. Systems chemistry G. Ashkenasy, T. M. Hermans, S. Otto, A. F. Taylor, Chem. Soc. Rev. 2017, Chair of the Action 46, 2543. E: [email protected] 2. Transient compartmentalization of RNA replicators prevents extinction due to parasites. W: http://www.systemschemistry.com/ S. Matsumura, A. Kun, M. Ryckelynck, F. Coldren, A. Szilágyi, F. Jossinet, C. Rick, P. Nghe, E. cm1304/ Szathmáry, A. D. Griffiths, Science, 2016, 354, 1293. 3. Transient assembly of active materials fueled by a chemical reaction. J. Boekhoven, W.E. Hendriksen, G.J.M. Koper, R. Eelkema, J.H. van Esch, Science, 2015, 349, 1075. 4. Diversification of self-replicating molecules. J. W. Sadownik, E. Mattia, P. Nowak, S. Otto, Nature Chem. 2016, 8, 264. 5. Dissipative self-assembly of vesicular nanoreactors. S. Maiti, I. Fortunati, C. Ferrante, P. COST (European Cooperation in Scrimin, L. J. Prins, Nature Chem. 2016, 8, 725. Science and Technology) is Europe’s 6. Enzymatic reactions in confined environments. A. Küchler, M. Yoshimoto, S. Luginbühl, F. longest-running intergovernmental Mavelli, P. Walde, Nature Nanotechn. 2016, 11, 409. framework for cooperation in science 7. Emergent catalytic behavior of self-assembled low molecular weight peptide-based and technology funding cooperative aggregates and hydrogels. M. Tena-Solsona, J. Nanda, S. Diaz-Oltra, A. Chotera, G. Ashkenasy, scientific projects called ‘COST Actions’. With a successful history of B. Escuder, Chem. Eur. J. 2016, 22, 6687. implementing scientific networking 8. Common origins of RNA, protein and lipid precursors in a cyanosulfidic protometabolism. B. projects for over 40 years, COST offers H. Patel, C. Percivalle, D. J. Ritson, C. D. Duffy, J. D. Sutherland, Nature Chem. 2015, 7, 301. scientists the opportunity to embark 9. The systems perspective at the crossroads between chemistry and biology. A. de la Escosura, upon bottom-up, multidisciplinary and C. Briones, K. Ruiz-Mirazo, J. Theor. Biol. 2015, 381, 11. collaborative networks across all science 10. Stability and its manifestation in the chemical and biological worlds. R. Pascal, A. Pross, and technology domains. For more Chem. Commun. 2015, 51, 16160. information about COST, please visit www.cost.eu.

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