Congratulatory post: Hail to the Imperial 2016 iGEM team!
By Ismael Mullor-Ruiz
With a bit of delay, we as a team would like to join in the congratulations for our colleagues and collaborators from the Imperial 2016 iGEM team, who triumphed at the iGEM 2016 Giant Jamboree at MIT.
For those who aren’t familiar with it, iGEM (acronym for “International Genetic Engineered Machine”) is the world’s largest synthetic biology contest. It was started 12 years ago at MIT as a summer side-project in which undergrad teams designed synthetic gene circuits never seen before in nature, built them and tested each of the parts. Many of these parts have subsequently pushed forward the field of synthetic biology. Even though it began as an undergrad-level competition with only a handful of teams involved, the competition grew larger and larger to include not only undergrad teams, but also postgrad teams, high school teams and even enterprises. More than 200 teams from all around the globe that took part on the last edition.
Traditionally, synthetic biology involves tinkering with a single cell type (eg. E. coli) so that it performs some useful function – perhaps outputting an industrially or medically useful molecule. This tinkering involves altering the molecular circuitry of the cell by adding new instructions (in the form of DNA) that result in the cell producing new proteins/RNA that perform the new functions. The focus of this year’s project from the Imperial team was on the engineering of synthetic microbial ecosystems of multiple cell types (known as “cocultures”) rather than a single organism, since more complex capabilities can be derived from multiple cell types working together.
So they began by characterizing the growing conditions of six different “chassis” organisms and creating a database called ALICE. The challenge here resides in the fact that the different organisms had different growing conditions and thus maintaining a steady proportion is really hard to achieve; typically one of the populations ends up taking over in any given set of conditions. Thus, in order to allow self-tuning of the growth of the cocultures, they designed a system consisting of three biochemical modules:
1) A module that allows communication between the populations through a “quorum sensing” mechanism. Population densities of each species are communicated via chemical messengers that are produced within the cells, released and diffuse through the coculture. Each cell type produces a unique messenger, and the overall concentration of this messenger indicates the proportion of those cells in the coculture.
2) A comparison module that enables a cell to compare the concentration of each chemical messenger. The chemical messengers were designed to trigger the production of short RNA strands in each cell; RNA strands triggered by different messengers bind to and neutralize each other. If there is an excess of the cell’s own species in the coculture, some of the RNA triggered by its own chemical messenger will not be neutralized, and can go on to influence cell behaviour.
3) An effector module. The RNA triggered in response to an excess of the cell’s own species is called “STAR”. It can bind to something known as a riboswitch (see figure below); when it is present, the cell produces a protein that suppresses its own growth. Cells therefore respond to an excess of their own population by reducing their own growth rate, allowing others to catch up. The approach of using a riboswitch for cell division control presents several advantages as its ease to design and to port at any cell type, and involves a reduced burden on the cell compared to other mechanisms.
Figure 1: Action of STAR in opening the hairpin of a riboswitch. Without STAR, the riboswitch interferes production of certain genes; STAR stops this interference so that the genes are produced.
As a demonstration of the concept, the students implemented this control system in different coloured strains of bacteria in order to create different pigments (analogous to the Pantone colour standard) through the coculture and combination of the strains. The approach is very generic, however, and as the team mention on their wiki, the possibilities of cocultures go way beyond this!
If you want to know more about the project, you can check out the team’s wiki: