The International Genetically Engineered Machine (iGEM) competition is a worldwide competition in the field of synthetic biology, where teams from universities around the world come to compete. The competition started in 2004 at M.I.T as a course, expended into a competition around 2006, and by 2017 there were 300 teams worldwide.
As part of the competition, a group of undergraduate and graduate students have the unique opportunity to come up with a research proposal that interests them. They are also in charge of raising the required funds, planning the appropriate experiments, conducting them in the lab, and presenting the project in the final competition in Boston. All with the help of faculty members and graduate students that guide them through the process.
The first Israeli team was established in 2012 at the Technion under the guidance of Assistant-Professor Roee Amit; the team won a gold medal in the regional competition.Since then, four teams have participated, with the 2015 team having multiple achievements, including Best New Application award, a gold medal, and finalists for Best Presentation, Best applied Design, and Best New Basic Part. The 2017 team will be participating this November.
In our group, we strongly believe in iGEM as a platform to not only introduce undergrads to the rigors of research, but also in the power of play to produce interesting new research and synthetic biology applications. All Technion iGEM groups have produced such viable novel research directions.
iGEM Technion 2016
Digital chemotaxis 2016
iGEM 2016 decided to focus on detection, which has been one of synthetic biology’s areas of focus. However, they decided on taking on a different approach. Realizing that detection based on binding affinity is subject to both noise and interference from non-specific binding cannot be used to detect extremely low titers of proteins or other non-nucleic acid bio-molecules (nucleoic acids can have ultra-specific recognition due to Watson-Creek base-pairing), they opted for a different approach. They wanted to explore the potential of gradient detection as in chemotaxis. Unlike concentration, which are fixed, gradients can be manipulated (e.g. by microfluidics devices for example), and as a result a much more reliable detection of lower concentrations of molecules can be achieved. In addition, they realized that bacterial chemotaxis is a form of broad-band technology for chemical detection that evolution harnessed for the precise use of E.coli and other bacteria.
In order to harness it for human application the group set up an integrated approach:
1) Tare down the natural E.coli system, and build it back up again with receptors that will respond to organic molecules that are important for human applications.
2) Construct a rapid detection device which can immediately give a signal if a particular molecule is detected.
As for the first part – taring down is easy, but building things back up is always hard. Fortunately, unlike two-component signaling, chemotaxis is more amenable for engineering due to its pleiotropic or promiscuous kinase component, which interacts with multiple receptors (Need a figure here, which compares two-component and chemotaxis – take from iGEM). This promiscuity has made generating new receptors in E. coli simpler than expected. During the project the group was able to fuse to Tar (natural E.coli receptor) either GFP or PctA giving it a new response capability. In particular with PctA the group was able to identify a new repellant, which was only previously suspected but now shown.
In order to engineer completely novel receptors the group (spear-headed by Computer Science undergrad Inbal Adir) employed the Rosetta package to predict mutations into the Tar receptor, which will enable detection of Histamine. Histamine is an amino acid derivative for which E.coli never evolved any detection apparatus. The model produced 11 high-confidence mutation predictions. Those sequences were ordered from IDT, cloned, and tested for histamine response. One clone responded as a repellant using Swarming and the Digital chemotaxis assay.
Chemotaxis is normally detected via large-scale assays that look at swarming of bacteria inside fluid chambers. In order to facilitate a more rapid and digital detection, the group in collaboration with Prof. Esther Segal’s group develop a digital chemotaxis assays. To do so they harnessed the Segal group’s porous silicon platform, and its ability to trap bacteria in wells to detect chemotaxis in a unique and rapid way. If an attractant was applied to the chamber the cells swam out of the wells generating an optical signal (positive), but if a repellant was applied the cells swam deeper into the wells generating a reverse (negative) optical response. The figure shows that the response are rapid (~5 minutes) and are digital.This work is continuing in collaboration with the Segal group to generate a broad-band digital detector of multiple organic solvents.
iGEM Gold Medal
Publisher paper: Demonstration of de novo chemotaxis in E. coli using a real-time, quantitative, and digital-like approach
iGEM Technion 2015
With the recognition in recent years of the importance of microbiome to human health and disease and it interaction with our immune system, it has become apparent that if we could manipulate our microbiome by either engineering new populations or harnessing it to become a personalized “24hr/7days a week” pharmacy, we can then not only be able to produce the necessary drugs to keep ourselves healthy, but also continuously monitor our health on an hourly basis.
The idea of iGEM 2015 is to perturb the skin microbiome by re-introducing a natural component (B.subtillis) that was slightly altered. The alteration is to get it secrete an enzyme that if delivered directly to the root of the hair will stop hair-less in men and women.
This project has now advanced past the conceptual stage, and we are nearing experiments on real live animal models. This project is being carried out in collaboration with Asst Prof. Boaz Mizrachi here at our faculty.
The first part of the project was to get B.subtilis to secrete the 3α-HSD enzyme, which is the enzyme that can hydrolyze the testosterone product DHT, which is thought the be responsible for hairloss. The hydrolysis of DHT converts it the harmless produce 3α-Androstanediol. We scanned a library of over 60 secretion peptides, and found several strong secreting strains, which exhibited strong enzymatic activity in the extracellular milieu.
We are starting to test our strains on porcine skin samples, and will be moving forward to animal models soon.
Best new application Project
iGEM Gold Medal
Patent: US provisional patent 62/396,167
iGEM Technion 2014
Light-sensitive synthetic biofilms
An emerging thread in synthetic biology research to is to couple living cells to chemicals or ligands of some sort to generate novel systems that are not entirely based on genetically encoded modules. Here we wish to use light-sensitive molecules to bind and unbind to cells based on illumination by a particular wave-length. The light-sensitive molecules, will then trigger the formation of multi-cellular structure, which can be disassembled by a simple exposure to an”off” wave-length.
Won iGEM Gold Medal
iGEM Technion 2012
Building a multi-part gene-expression system for orthogonal gene expression in mammalian cells
As synthetic biology application become more complex, the need to decouple the synthetic circuit from the natural transcriptional machinery has many advantages. First, the load on the natural gene expression apparatus will be reduced, and second the likelihood that unintended fatal disturbances to the natural systems will be reduced as well.
In addition, a synthetic gene expression apparatus can be controlled using external input signals, which would allow it to turn on if and only if a particular set of inputs is encountered.
We do this in yeast and mammalian cells.
Won iGEM Gold Medal