The Heidelberg iGEM team was this year’s Grand Prize Winner at iGEM, a premier undergraduate synthetic biology competition held annually in Boston. Dr. Roland Eils, the team’s advisor, spoke about his team’s project and the overall experience at iGEM. Dr. Eils founded the iGEM team at Heidelberg in 2008. From then on, he has been the team’s mentor – recruiting students and advisors, supporting the team, and giving advice.
“Every year I have done (iGEM) I’ve invested an enormous amount of time into it. It was a lot of work, everybody had to invest in it, including the instructors, the advisors, and of course the students themselves”.
Heidelberg’s iGEM’s project is called the Ring of Fire, and aimed at circularizing proteins in order to make them more stable under heat. As explained by Dr. Eils, proteins are the major workhorses in cells and are important for almost any process in the human body. Proteins are made of chains of amino acids, which have a distinct beginning and end and are folded into a 3-D structure. This structure is important because it allows the protein to perform its function. However, the beginning and the end of these chains are also weak points, where a protein can get degraded. For example, a protein heated beyond a certain point may experience heat-shock and lose both its structure and function. To address this issue, the team decided to stabilize proteins by fusing together the beginning and the end of the chain, thus making a circular protein. These so-called circularized proteins exist in nature, and tend to be more stable than non-circularized proteins. According to Dr. Eils, “the idea was that if nature has invented this for a very small subset of proteins, why not take this idea forward and come up with a standardized method to stabilize any protein of interest”. And so, the team developed a tool kit that allows scientists to circularize any protein using a standardized procedure.
One challenge the team faced was preserving the 3-D structure of the protein being circularized, so that it is still able to function properly. To this end, the team developed a software system, called the Linker Design software, that can predict which linker molecule is best to use in order to link the two ends of the protein so that its structure is preserved. “We showed, for a number of proteins with very different applications, that the predicted model was the right way to circularize them. We also showed that under heat the circularized proteins are still active, which is a very remarkable contrast to the linear form of the protein.”
But why is protein-stability under heat so important? As Dr. Eils explained, heat is an important factor in almost any industrial application in biotechnology, which limits the production of many products because it destroys the proteins used in these industries. So, stabilizing proteins under heat-shock is a valuable tool and can be used in hundreds of industries to create more products in a more efficient manner.
While working on this project, the team also developed another software called iGEM@home. According to Dr. Eils, this software was a side-product, developed more from necessity than as part of the original project. When working on the Linker Design software, the team had to run many computations, some of which were extremely expensive. In order to mitigate the cost, the team developed a distributed computing platform, which uses the computing power of idle home computers to run large-scale analyses. Volunteer users simply had to sign up and download a small piece of software, which would link their computer to the Linker Design software and use those computers’ computing power to run the software. In return, when the software runs on idle computers it displays screensavers dedicated to teaching the public about synthetic biology. Overall, the value of the iGEM@home cloud reached $23.000 US per month on the Amazon cloud, and the software displayed about 40 thousand screensaver slides, allowing the team to work on their original project, as well as to educate the community about synthetic biology. Best of all, the Heidelberg team has made the iGEM@home software available to other iGEM teams, so that future teams will be able to afford to run large-scale analyses and work on computationally-expensive iGEM projects.
Talking about his team, Dr. Eils emphasized the fact that the idea and design of the project are exclusively the responsibility of the students themselves. In general, although mentors offer advice and guidance, the students are left to themselves to develop their own ideas. In order to achieve the kind of complexity and variety seen in Heidelberg’s project, the team is very multidisciplinary. The vast majority of students are in their second or third year as undergraduates, yet their focus spans experimental biology, physics, computer science, theoretical modeling, and even neuroscience. Eils feels that everyone who participates at iGEM gains from the experience.
“The students themselves have expressed that it is not only the best part of their school experience, but that what they learned through the course of the iGEM project was much more important than the sum of everything else they learned in their regular courses.”
By exposing students to high-level research, scientists from around the world, and the opportunity to present and defend their ideas, the iGEM competition is an incredibly valuable experience, both for students and for the field of synthetic biology as a whole.
For more information on Heidelberg’s iGEM project, visit their website.
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