iGEM 2010: Interview with Simona Constantinescu

The historical start of the International Genetically Engineered Machine competition (iGEM) goes back to January 2003. In 2010, the student event was hosted by the MIT in Boston. One of the participating students was Simona Constantinescu, CBB Master student and Excellence Scholarship recipient. She and other seven fellow students won with their project “E. lemming” the first prize in the category “Information Processing”. In this competition, biology students learn engineering approaches and tools to organize, model and assemble complex systems, while engineering students are able to immerse themselves in applied molecular biology. I have talked to Simona about this growing, yet not so new research area. And needless to say, she has shared, of course, the exciting time at MIT, the challenging competition and her learning experiences.

Simona, to be honest, for nearly 40 years, genetic engineers have been decoding DNA and transplanting individual genes from one organism into another. Synthetic biology is not really a new science, isn’t? Nevertheless, why is this still burgeoning field the coolest thing in the universe for you?
Looking one and a half years back, during one of the first CBB Master lectures, I remember my first conceptual encounter with the biological systems as I see them now: hugely entangled, incredibly complex and seemingly-chaotic-but-actually-scarily-ordered. This encounter brought about a mixture of surprise, respect and, primarily, curiosity towards the study of biological systems. Since then, I became more and more interested in understanding these systems and, mainly, understanding why they are so challenging to understand. Finding Systems Biology such an interesting field, I also wanted to know more about Synthetic Biology, which pushes the analysis phase one step further: towards the creation phase.

The techniques Synthetic Biology uses are indeed not novel. Nevertheless, what Synthetic Biology brought new during the past years are first the possibility, which just recently became large-scale available, of de- novo DNA sequences creation and second, the aim of deriving novel functions and equip the already existing organisms with them, creating in this way new organisms.
This goal is achieved in a very methodical way: the individual DNA pieces responsible for certain functions (named 'parts') are “uploaded” and stored in a universal database, which desirably anyone interested in Synthetic Biology can access. It is up to one's own imagination and courage which parts to “download” and how to combine them. By using the already existing parts for new projects, with new goals, completely novel parts are created, which are also uploaded. Therefore, as an intrinsic property, the system itself is continuously changing and improving. This is so cool because it makes you feel like the creator of the world you are working with.

As commercial applications for this kind of science materialize, the hope is that synthetic biologists can engineer new, living tools to address our most pressing problems. Also, a legacy of iGEM is to create an inspiring atmosphere, a can-do fervor propelling this science forward. Did you feel a bit like being part of something bigger than yourself at this event?
The Jamboree iGEM Meeting at MIT was impressive. Irrespective of the stories the former iGEMers had told us about their Jamboree experience, it is one of the things you can only understand once you live them. Students from more than 130 teams all around the world, with initial backgrounds varying from biology to mathematics, exchange their Synthetic Biology experience and ideas, opening up the way to new connections and collaborations. They all have in common the enthusiasm and belief that this new emerging field will reach its goal of non-fictively changing the world we live in, by somehow devising automatic ways to improve and, why not, completely change many of its pressing actual problems. I do believe it lays in our responsibility, as iGEMers, to propagate this enthusiasm further and to raise the awareness on how many future possibilities Synthetic Biology offers.

For me, one of the nicest moments at the Jamboree was the poster session, where I had the chance to get an insight on other projects and discuss with other students. Also, people were very interested in the details on how our project actually works. Some of the questions were really challenging and they varied from pure biological details to tricky mathematical insights. The event gives you a sort of fever which then stays on, together with the remaining impression that not only everything is possible, but YOU are the one who can do it.

The story of iGEM begins not with biologists but with engineers. For them, it is a chance to work with the most awesome material around: life. What were your particular contributions as a computer scientist in this E. lemming project?
As a theoretician, I found myself in a completely different setting than everything I was used to before. After deciding on the project idea, the entire team encountered a crazily complicated system, behaving randomly within certain bounds, which not only we hadn’t built or designed, but also extremely high chances were that noone on Earth knew all the details on how it actually works. Our challenge was to make the system guidable.

In the E. lemming project, I was part of the theory subgroup, therefore in charge of the modeling and computational simulations of our tiny robot. My task was to simulate realistically the chemotaxis motility. We linked the changes in light wavelength with the changes in bacterial motility. The modeling of the system also aided in the optimal design of the wet lab experiments, by selecting the most sensitive target proteins out of 81 possible constructs and therefore substantially speeding up the process. In the end, we saw the tiny living robots moving the way we wanted them to move. And, even if this might sound evil, it is far from being so. It is rather the feeling: Things are literally being discovered under your eyes and, in some of the times, you are the actual one discovering them!

Let’s think half a century ahead, what do you think how your research findings can make their ways to practice? How can these tiny, remotely controlled living robots be practically used?
Well, Minh, you will certainly hear more and more on Synthetic Biology during the years to come. Still, I think the main complexity threshold is yet to be overcome, and that substantial effort and creativity are required on both the computational and the biological side to implement all the existing ideas into practice.

Thinking ahead, tiny E. lemmings could be used for intercellular transport of substances (such as drugs or diagnosis substances) to specific locations. The advantage of our robots is that they can be guided on any user-defined path, which can also change during the transportation process. With a visual monitorization system showing at every timepoint where the E. lemmings are, one could guide the robots on the spot, depending on their relative position with respect to the destination point. The advantage of using light and not using chemoattractants, as in the original chemotaxis settings, is that light is a stimulus which can be easily, cheaply and very fast perturbed, resulting in changes in bacterial motility.

Nevertheless, as it generally happens with ingenious projects, one sees the coolest applications years after the initial idea was set up. Therefore, the road is open to novel interpretations...