The Paris-Bettencourt-Calgary iGEM collaboration started last June when a few members from each team met at the SB6.0 synthetic biology conference in London, England. After a few beers and lab stories, we learned that despite coming from the opposite sides of the globe, we were both using synthetic biology to build biosensors to sense DNA. Each of our own systems targeted different problems, but we were struck by the number of commonalities between these projects. See the Figure 1 for a breakdown of these differences.

Figure 1. The Calgary and Paris Bettencourt biosensors both sense DNA, albeit with some differences in how they function mechanistically.

As we talked about our projects and discussed our adventures searching through iGEM, we agreed that there is a lack of DNA biosensor components in the Parts Registry. We were thus excited by the possibility of developing modular DNA sensing platforms that future iGEM teams could repurpose for other problems. Moreover, we found the lack of organization of biosensors in the registry frustrating. Each teams veteran iGEMers mentioned that biosensors had consistently finished as grand prize winners in previous years of iGEM. This left us curious as to how biosensors had evolved since the beginnings of iGEM and how each of our current projects fit into the greater context of the iGEM Parts Registry.

SensiGEM - A biosensor database

To get an answer to this question, we built a collaboration between our teams. Since our initial meeting in London, members of each team have tele-conferenced weekly on Skype. After accustoming ourselves to the eight hour time difference, we developed SensiGEM, a collaborative database in which we could catalogue all the biosensors in the history of iGEM.

Before sinking our teeth into past Wikis, we realized that we had different definitions of biosensors. We asked each other a fundamental question: What is a biosensor? We developed the following definition:

A biosensor is an engineered system that relies on biological systems or components to detect and report a condition. The condition(s) detected and reported could encompass an environmental, biological, chemical or synthetic aspect or compound in the sensor’s environment or surroundings.

Once agreeing on the nature of biosensors, we split up the Wikis from 2007 onward between Calgary and Paris-Bettencourt. We analyzed 936 project Wikis from 2007 to 2013 by hand, incorporating the projects which matched our biosensor definition into the collaborative SensiGEM database. We included 229 projects on the database, some of which were biosensors as per the definition, as well as other projects containing biosensor elements that aligned with our definition.

We designed this database with future iGEM teams in mind, with tools for efficient navigation biosensors according to inputs, outputs, and their intended application. We made both SensiGEM's source code and underlying data available under the permissive MIT license. This means that other teams can either collaborate with us on our version of the database or host their own independent copies. We foresee SensiGEM as a resource where future teams can effectively assess biosensors developed previously in iGEM and find components that they can harness in new projects. Additionally, we want to see iGEM teams showcase their biosensors in a single location.

Lessons from SensiGEM

We conducted some preliminary analysis of the database in SensiGEM to see how our projects stand in the current iGEM biosensor landscape. Please see Figures 2 and 3 below.

Figure 2. The approach Calgary has taken using an in vitro sensor comprised of isolated, non-living protein components is rare within iGEM. There was an all time high of 12 of these projects in 2010.

Figure 3. Since 2007, fewer than 10 iGEM biosensors involve inputs of nucleic acids. Henceforth, Paris-Bettencourt and Calgary are significantly expanding the variety of nucleic acid biosensors in the iGEM registry.

In Figure 2, we can see that Calgary's approach of using non-living, in vitro protein components is not typical of biosensors in iGEM. We advocate this approach for two reasons. Firstly, we envision components such as our robust ferritin reporter as being more field stable compared to systems in living cells. Secondly, our system overcomes potential concerns of deploying synthetic bacteria in the broader environment since there are no living components in our sensor.

From Figure 3, we have can see that 5 DNA biosensors were added to the iGEM Parts Registry since 2007. This means that about one half a percent of projects since 2007 were DNA biosensors! Since Paris-Bettencourt and Calgary are launching two novel DNA sensing components, we are significantly expanding the variety of DNA biosensor tools in iGEM. Moreover, each of our respective systems are modular and can be modified to sense most any DNA segment of interest, which means that other teams could use apply these components to a variety of applications.

Future directions

Each of our system's are similar in how they are modular and can be adapted to sense various DNA sequences. We are considering developing Biobricks to implement each system to the other team's respective problem. Such work would serve as an example of how each system can be deployed as a modular, platform technology.