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:
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