 So, we have been asked by the organizers as chairs of the different sessions not only to chair and control the time and so on but also to put some perspective in the contents of the various topics that will be discussed by the different speakers. So I take this opportunity to also share with you some of my thoughts on the matters that we will be discussing today and the next few days and also to warm up a little bit the subsequent presentations. So I have been asked also by the organizers that to ask you as an audience to please refrain from asking questions on the spot after the different presentations but just to postpone them until the general discussion that will take a good 40 minutes after each session so we have time to not only to interrogate and to ask specific questions to the different speakers but also to raise more general questions for a more general discussion as well. And this is exactly what I wanted to do this morning as the first little presentation or the first little talk that you are going to have. So I will not be discussing the work that we make in my laboratory directly with the details and so I just want to share with you some thoughts that were provoked by the program once I had the chance to see in the different contents and different speakers and so while I come from Madrid as I told you this is the National Center for Biotechnology some of you have been visiting there and well the matter and the object of this of the subject of this whole meeting for this week is synthetic violin so every meeting of synthetic biology may start with some discussion of what is synthetic violin I will not get into that but I want just to remind you that the term synthetic violin was coined in France maybe with a different meaning but indeed the term is not new despite some claims and it has been around for a while but it has been subject to different trans significations and in the most modern and the most popular meaning is about engineering biology and doing things connected to interfacing biology with biology but I want to go a little deeper into this question so as a matter of fact I think that the starting point of synthetic biology is this reaction that we may have when we find a complex object okay so when you are in the wild and you find something that is there you don't know very well how it works there are two legitimate questions that you may want to raise and one of them is where does it come from and second how it works and you know I think that in biology we tend to come to to mix these two questions and from my perspective they are completely different one thing is to ask the origin of things and they're into us how these things work okay so in biology and there's this general say theory evolution combined with the mother genetics and the two pillars of modern biology are the ones that you see there on the one hand the Arbenian evolution and all the rest of it and then the central dogma through which DNA goes to RNA goes to proteins and if you want also it goes into metabolism so the main argument that I want to try to convince you and your way welcome to disagree is that in fact evolution is great as a conceptual friend to understand by only but it does not help us to understand how things work they tell us where they come from but not so much how they work so how a valuable entities come to work well there's this concept that was developed by frangiole of Jacob also in in Paris in the past institute that is called tinkering in English I have to say that the word recollage in in in French in my opinion is not identical to the word tinkering in in English but still you know there's this idea that the evolution just you know it takes one thing that is available it was it to another thing and then it works and then somehow it can be hooked up to another thing a little by little you end up having something that works and this is what we see in a biological objects today however I have the impression that if you take this a concept to a seriously at the end you end up with this kind of grotesque situation that is exemplified by the cartoons of Rube Goldberg and this idea you can concatenate you can link various events and at the end get something working but at the end the way and the process that brings about the the outcome is very weird so for instance in this cartoon and there are many like this the question or the challenge is to wake up that the entomal there and then the way to do it is that you have that bird that let me see if this works here so you have this the day rises and you have this bird that eats a worm then there's a thread here that will get a pistol and the pistol will get into a balloon then a brick that we will go into this perfume box then it will release some vapor then there's a sponge that will come down and then at the end it will be this this cannonball that will go in the face of the guy there so sometimes what has the impression that in biological system you have something like that so as a matter of fact maybe this is not sufficient to understand how things work because of this phenomenon that in evolutionary biology is called expectation so expectation means that one object to one biological object that appears in evolution to fulfill a given function in the next stage of evolution it may go into a different completely different function and the example are feathers for instance so feathers were say invented to provide thermal insulation to dinosaur but they were invented for that but their major evolutionary outcome had nothing to do with thermal insulation had to do with flight okay so the fact that you know how something works at one stage of evolution will tell you nothing of how it works in the next stage and therefore here comes my argument that by following the genealogy of different biological objects we in reality we don't understand we may not understand or it does not help as much to understand how these things work then here comes synthetic biology so synthetic biology from my point of view is about doing things and all these wonderful papers with Cas9 and CRISPR and everything but I think they have a more profound scientific impact because it's no more and no less that taking a look to life systems using engineering as a interpretative frame so from that perspective you know like by the same token that molecular biology was born out of the interest of physicists and in some cases nuclear physicists for biology in synthetic biologists from the interest of engineers real engineers to look at biological systems using their own interpretative frames their own concepts their own even their own materials so this has serious consequences okay because depending on what frame one uses to understand things the kind of consequences and their resulting agenda might be quite different so engineering as an interpretative frame can be used for understanding then we can look at biological objects looking at their for instance and their composition at their relational logic and other aspects that perhaps only engineers have looked at from that perspective also of course it's about doing and this is doing and creating and the two more visible say outcomes of synthetic biology but let us not forget that there is this big aspect and this important aspect of using engineering as a frame as a tool for understanding the state of affairs and this is something that I like very much so we can return to biological systems and look at them as if they had a relational logic that explains its function and this is the twist that I think is important in the case of synthetic biology the emphasis is not in the evolutionary origin of things is in the composition and relational logic of the things that makes them to work here and now and you know that changes a little bit the historical say drive for biologists to be interested in evolution and to just concentrate in understanding the original things the twist now is to concentrate in how things work and whether we can improve the way of working and whether we can even create things that using biological components still will work in a different fashion so the consequence of adopting this engineering frame is the kind of discourse that you may have seen in many places this is a typical slide that is shown in every talk on synthetic biology how in synthetic biology we adopt the abstraction hierarchy that is typical of engineers we start with parts then it goes into devices and it goes into systems and then you get all these nice say narrative of contemporaneous synthetic biology and the consequence of that is that whereas in the in the in traditional biology you have a central dogma that tells you that DNA goes to RNA and so on in the case of synthetic biology the dogma or the tenet it changes a bit and now the question is not to understand this flow of information the question is to understand how parts make devices how make eventually models and perhaps systems and by the same talking that we understand then we can also recompose them and generate new properties and this is something that is the kind of I say big core of synthetic biology so the situation is that we want to start with an existing system then by using this plethora of omics approaches one ends up with a collection of parts and then you can make a model and then you go into the cycle or you can go out of the cycle and using the same parts with the characteristics and so and produce objects that are not exactly what you had at the beginning but still they follow a relational logic that follows the the kind of tenets of engineering so here comes now the interesting challenge for synthetic biologists that is how to construct complex objects and one can take a look to biological systems as complex objects and the challenge to first to understand how they were but also how to rearrange their connectivity and their forms and their parts and their layout to produce a different still complex object so here you have what one engineer would look at in the case of biology things can get a little more complicated because of various things the main thing is this issue of how to connect how to add different functions in a complex system in such a way that at the end the whole system works so biological systems are actually connected everything or not everything but many components of a system is connected to the others directly and directly you have these systems these actions at a distance and so so you can know a lot about the composition of different parts for instance in this case you have a pathway that you want to build for conversion of this substrate into its product here and it goes through a series of steps and you may have all types of information about the regulator the promoter the everything but at the end you put them together and it doesn't work and it's simply because you have to optimize many many many things at the same time so how do you handle this problem or this challenge of optimizing many many things at the same time well the typical engineering approach is that first you define what you want and then at the end you go into a type of design and then you have to explore a solution space that in many cases involves an iteration of having a prototype then testing the prototype and then it doesn't work identify the problems then you have to fix it and so on and so on and at the end you end up with something that seems to work well how can we do that in biology in biology keep in mind that we have an extreme complexity it is difficult to isolate with some parts of that complexity into separate models even though there's this concept of orthogonality that in some cases is able to do that but in many cases the optimization of a system that you engineer as a whole in biology is very very complicated so I have to take you into a different scenario that perhaps can give us some inspiration on how you can really handle this creation of massive complexity on the basis of what we know to do so the example I want to show you is this building that happens to be in Barcelona another hiring there based so-called the Sagrada family it's a cathedral that was started to be constructed in in the late 19th century 19th century means no computation no simulation no complex mathematics however if you look at this building it's really really extraordinary if you get inside then you find all these amazing architecture inside with the heights that are you know connected and everything and the important thing is that if you take a closer look you see very very few straight lines everything has like strange angles here and you know and you have an extreme complexity here of connectivity that makes the building to go up so this is a case of an architectural object an engineer object that had to had extremely complex a lot of dimensions of parameters had to be calculated with no or very little mathematics and no or very very little computation well no computation at all because computers have not been invented by that time so if you visit the place and I invite you to get there and you know is really amazing now how can you construct this amazing complexity with so little mathematics okay so this was the gentleman Antonio Gaudí that took this brilliant idea instead of making a mathematical model and making and follow the way that engineers and architects will follow let's do the following I'm going to make a model with strings and weights and then I put the dimensions that I want to introduce into the complex system and then in the strategic points of the building of the model I just put a weight here and then I just let the gravity to make the job of calculating what is the best distribution of angles and dimensions and curves that will give this structure stability so this is a model for instance you can see in if you visit the place in Barcelona and then well they have the weights and everything so what he made that is that when you have this model all you have to do is to turn it upside down and immediately the gravity will tell you the solution to your problem so no mathematics no simulation just gravity and embodiment of the construction challenge in a physical object and this is something that in my opinion can be very inspirational to take the challenge of constructing biological systems without the real complexity without really understanding and knowing every single parameter involved in the challenge so in more say strict terms this has been called in some cases heterotic computing and heterocomputing is this idea that you raise a problem but instead of solving it through mathematical computations or mathematical calculations what you do is that you embody the problem in a physical object and then you introduce into the obvious and type of physical say action and then the result of that is not a number is not a parameter it's a physical measure so and this is something that you know in it forms part of traditional technologies and and so on but at the end is as useful to find the solution of a complex problem as any other say more rigorous and more mathematical approach so one of my kind of propositions for a discussion in along the meeting is that perhaps we should not be too paranoid on having controlling every single aspect of the design of a physical of a vertical object because at the end we may not be able to make it but it's still trying to be creative and find solutions to the problem of designing multi-scale complexity perhaps by using other methods that indeed have been used by other individuals that have been challenged with the problem of constructing these type of things and at the end you know you get these amazing structures again no computation very little mathematics so then here comes this idea that perhaps at the end of the day the challenge of evolution is not so different of the challenge of engineering and you might be aware that in some cases engineers themselves are able to find solutions to very very complex problems not by again making calculations but by developing some type of evolutionary algorithms that will find the solution to a multi-task or very very complex problem in this case these are some antennas that were developed by NASA for one of their missions and the idea instead of having a kind of top-down design of the corresponding antenna was to develop some evolutionary algorithms that little by little will change the shape of the antenna into something that was completely optimal for the role and this is the ultimate design you see that you know it's very weird I mean it's not the type of antenna that you would expect to have made by an engineer but still this is the best option that you have there so at the end what happens is that if you translate that into synthetic biology you can think in terms of optimality also by using this type of heterodic computing so for instance you have a pathway for production or degradation of one compound here and you have to have all these steps being run properly with an optimal say action and so on then how can we implement this type of heterodic computing in biological systems well there are various procedures or various ideas around to do it the idea would be to start putting together the basic components then try to connect them of sorts in some one way but then and this is the most important once they are connected you put some weights and we'll discuss in a moment what these weights might be in biology you let the system to evolve to get the optimal and then you manage to get the data from this say the formation of the object into something that has a perfect design and therefore in principle a perfect functionality so one possibility and this is more technical and these are the type of things that modern synthetic biology can do for you you can for instance start by defining a pathway and then the components of the pathway and you can connect the pathway through various connectors you need a promoter, you need a chandelier, you need intergenic regions and so on and then in strategic points of the pathway you have to introduce points where you put this weight and then this weight at the end is the one that will tell you the proportions and the characteristics of these intergenic spaces here that they will give you a degree of optimality so ladies and gentlemen this is basically what I wanted to to share with you these thoughts on how engineering biology might be easier that we think because even engineers and architects in the past have been dealing with the problem of constructing very complex objects by using kind of unconventional approaches and that's fine and I think that we should be happy to interface with our colleagues, engineers and mathematicians and discover perhaps ways of solving this problem that we could not figure out before if we just maintain ourselves in a real realm so I think that this is you know some ideas that will pop up throughout the meeting I just want to say a few words about the session for today so we will after I shut up then we will have talk by Paul Freeman so Paul Freeman comes from the Imperial College in London he's been amazingly instrumental to promote synthetic biology not only the UK but in Europe as a whole is what you may call one of the evangelists of synthetic biology at a global scale and he's been working a lot on the problem of standard synthetic biology he's been working a lot on the on the problem of formatting automated systems to monitor promoters and to monitor other scientific parts to generate the parameters on the basis of which one can really construct complex circuits and I'm sure that you will enjoy very much his presentation then we have these other topics by Daniel Tullman Erkek and by Ishiro Hirau that start giving us the type of flavor of the things that synthetic biology can do for us and how synthetic biology allows this repurposing of objects that nature gives to us in a given format or in a given function how we can really repurpose them to do something completely different or to enhance their properties or to use them in very fine context and viral capsids as you will hear during the the talk is one of these scaffolds that nature have developed for one given say function but in the hands of synthetic biology they can do amazing things as you will have the chance to see and finally we have this flavor on the world of xenobiology how you know we start with familiar biology with nucleotides with entramino acids with four bases and so on but then how we can start introducing and interfacing these natural systems with other molecules that are completely unnatural and still have synthetic systems and biological systems that work and do things that are new to nature so we're in that part of engineering that has to be with creation of new things and new properties and then we have a discussion and then that we have a long discussion and then well we'll have the chance to have some refreshment or whatever in the meantime we have some lunch or whatever well anyway in in in in any case I hope that this sets I'll be the frame of the discussions that in the best cases scenario should provide some inspiration not only to the biologists that are present in this meeting but also to the mathematicians and people that comes from for the physical science and these other hard science disciplines that's all I wanted to tell you ladies and gentlemen thanks for your attention and I will be happy to introduce Boothreem. Thank you