Congratulations to the Winning Teams from iGEM 2017

The iGEM “Giant Jamboree” is always an other-worldly experience. No other conference houses such concentrated innovation and enthusiasm for science.

This year’s gathering, held in November in Boston, Mass., marked the 14th iGEM competition, hosting 5 400 students from 310 teams covering every continent. Teams worked over the summer in the lab to develop a synthetic biology project based on a toolkit of standard parts provided to every team by iGEM. The Giant Jamboree is each competitor’s opportunity to showcase their hard work, with all teams competing for the grand prize and the coveted iGEM brick trophy.

The iGEM competition gives students the chance to be openly creative, to use open source tools, and to conduct scientific research out of the confines of grant guidelines. Every year, the result is huge innovation, rapidly advancing the synthetic biology field. Here we pay homage to the grand prize winners from each age category, taking a look into just how much can be achieved by students with some stock parts and a summer of science.

Taipei American School is a high school located in Taipei, Taiwan. This year, the team picked up their second victory in the high school category, after winning in 2015.

Their 2017 project was NANOTRAP, an engineered bacterium that can clean up pollution caused by nanoparticles. Nanoparticles are defined as any particulate with a diameter of between one and 100 nanometers in one or more dimensions – the biggest nanoparticles are approximately 750 times smaller than the width of a human hair.

Many of the products you use day to day can contain nanoparticles. Sportswear is often made to contain silver nanoparticles that can reduce foul odours with their anti-microbial properties. Tin oxide, and Zinc oxide nanoparticles are ultraviolet (UV) protective, so are used in cosmetics and sunscreen.



 

Although understood by science to be largely inert to humans, nanoparticles have been observed exhibiting toxicity to marine micro-life, marine plants and fish embryos. As hundreds of tons of nanoparticles are estimated to enter sewage works every year it is important that nanoparticle waste that leaches into the environment is minimized.

TAS Taipei tackled two key issues relating to environmental nanoparticle exposure. First, they noticed that there were no government policies specifically regulating nanoparticle disposal. The team therefore stepped up and developed their own policy documents to provide recommendations to policymakers worldwide. Taiwan’s environmental protection agency minister Lee Ying-yuan took interest in this document, stating that it will be taken into consideration in future nanoparticle policy decisions.

Second, the team noticed that there were no specialized, standardized procedures that allow for nanoparticle removal from wastewater. Their solution was to target citrate, a chemical added to nanoparticles in products to stop aggregation. The team engineered Escherichia coli to express a citrate binding protein on their surface. In addition, the team engineered a separate strain of E. coli that readily creates biofilms - a sticky agglomeration of bacteria and proteins.  Current literature suggests biofilms are able to trap nanoparticles, so the team hoped that by combining their citrate-binding bacteria with a biofilm, nanoparticles could be efficiently filtered.

Impressively, the team were able to validate that both their citrate binding bacteria, and their biofilms were able to trap nanoparticles. This is a burgeoning proof of principle technology, and it is clear that the team's extensive research and campaigns will likely have a significant impact on nanoparticle regulation and lead the way towards a better environment.

Vilnius University, of Vilnius, the capital of Lithuania, won their first grand prize victory, and their first ever special award (they took home 3!) at this year’s iGEM with their plasmid-focused project SynORI.

Plasmids are one of the most important tools in synthetic biology. These synthetic circles of DNA are used to shuttle new genetic material into cells, enabling genetic engineering. Team Vilnius found that although this technology is a cornerstone of the field, the technology has many inefficiencies that are limiting engineering research. These problems arise largely because plasmids are based on natural systems, and are optimized for use by cells, not by synthetic biologists! As a solution, the team then came up with SynORI, a new and improved plasmid system for synthetic biologists to use.

In a population of bacteria, plasmids are maintained by a small region in their DNA sequence called an “origin of replication,” which allows the cell to copy the plasmid multiple times ready to be passed onto future generations. The amount a plasmid is copied is called the “copy number,” and the copy number is generally controlled by the origin of replication. 

For synthetic biologists, copy number is important as it denotes the amount of engineered sequence present in the bacteria. There are various origins of replication that have been derived from nature, with various copy numbers, however plasmids are limited in that their copy numbers are fixed. There is no origin of replication available that can be tightly controlled. Such limitations to copy number and the origin of replication become problematic when more than one plasmid needs to be used as optimization becomes increasingly important in contemporary synthetic biology.

SynORI is team Vilnius’ solution to the plasmid problem – a toolbox of plasmids that contains engineered, controllable origins of replication. The team focused on engineering a system that controls the 3D structure of the DNA in the origin of replication, a key factor in its copy-number control. SynORI plasmids can be predictably controlled by adding a chemical stimulus to the plasmid containing organism’s growth media, allowing researchers to produce precise amounts of plasmid exactly when required.



 

SynORI also tackles plasmid incompatibility. Two different plasmids with the same origin of replication cannot be kept by the same cell. By engineering and characterizing new SynORI sequences, the team generated a complete toolbox of controllable, compatible plasmids so researchers can modulate multiple plasmids at once if required. 

However, the team didn’t stop there. The maintenance of more than 3 unique plasmids at once by a laboratory bacterium has rarely been achieved, as the system becomes increasingly more unstable with each new origin of replication. Antibiotics are usually used to keep an antibiotic-resistant plasmid in the cell, meaning each plasmid requires a unique antibiotic – a huge burden to the organism. The SynORI toolbox was completed with a new selection system that allows up to five tuneable, stable plasmids to be held by a bacterium simultaneously using only one antibiotic – a world first in synthetic biology.

Vilnius blew iGEM and the synthetic biology community away this year with such a huge foundational advance. Their tunable plasmids will enable better computer-based logic to be engineered into genetic pathways, as up to five plasmids can effectively be switched on and off in response to different stimuli. The technology developed in SynORI is a giant leap forward for those engineering complex synthetic systems, and will likely be used by iGEMmers and synthetic biologists in the foreseeable future.

Delft University of Technology, located in the south of Holland in the Netherlands, is a top 20 university for engineering worldwide and has competed in iGEM since 2008. After also winning in 2015, the team from Delft took home their second grand prize trophy in the overgraduate category for their innovative diagnostics based project.

Antibiotic resistance is a critical issue to humanity. By 2050 it is projected that 10 million casualties will come from antibiotic resistant infections each year if solutions aren’t found. One of the most pressing contributors to antibiotic resistance is the overuse of antibiotics in farming industry, especially in dairy, where mastitis (a disease of the udders) is common. Mastitis is treatable with antibiotics, but antibiotics are often used in feed to prevent onset of the disease. As a result, farms are a breeding ground for antibiotic resistant bacteria.

If a farmer wanted to check whether their cow had an antibiotic resistant infection, they would need to send samples off to be screened, which can take weeks – not good for the cow, or the other cows on the farm. Delft University of Technology’s iGEM project used a new enzyme from the CRISPR toolbox to solve this problem, producing a test that can be run in the field – literally.

Cas13a (formerly C2c2) is a protein related to Cas9, the DNA cutting enzyme typically used in CRISPR. Instead of seeking out and cutting DNA, Cas13a instead selectively cuts RNA molecules. When it finds an RNA molecule that matches its guiding RNA sequence, Cas13a makes a cut and, unlike Cas9, then becomes hyperactive, catastrophically cutting all other RNA sequences around it.

Delft’s iGEM team used catastrophic cutting as their visualisation tool. By designing guides that allow Cas13a to start cutting only when it finds RNA from an antibiotic resistant variant of an infectious agent, they had a differentiator between the presence susceptible and resistant strains in a sample. The team then continued by developing a way to simply visualize whether the RNA had been catastrophically cut or not.



 

Coacervation is a property of a solution containing positively and negatively charged polymers that form dense aggregates that turn a solution cloudy. Simple RNA polymers with lots of uracil form a cloudy coacervate when mixed with the polyamine spermine. If an RNA sample is added to the coacervate, with a Cas13a that specifically targets the new RNA sequence, Cas13a will catastrophically cut all uracil polymers which breaks down the coacervate. The solution then turns clear, signalling a positive hit. If the added RNA is not recognized by the Cas13a, the solution stays cloudy. 

The team packaged their new visualization tool into a safe-to-use kit that contained freeze dried Cas13a, the coacervate and tools to prepare milk samples for testing by hand. They then gave their toolbox to a milk farmer, who could get positive results from a sample of his own cow’s milk within three hours. Their project proves that synthetic biology is not only a vital application in the future of humanity, but is also able to be simplified enough to be used safely by anyone in the field. Hopefully, this is a glimpse of things to come for the field.

Twist Bioscience sends huge congratulations to all teams who competed this year – it is incredible to see huge innovation being driven forward by the next generation of great scientists. We also wanted to note the achievements of the five teams that Twist Bioscience supported this year, all performing exceptionally well in the competition. 

INSA UPS France won both best information processing project and best applied design. It was nominated for eight awards, and took home a gold medal.

Technion Israel received a gold medal.

Edinburgh UG was nominated for the best measurement, and won a gold medal.

Ashesi University Ghana won the Chairman’s Award, a prize that was last given out in 2014.  This award is reserved for teams who catch the attention of the iGEM Foundation Chairman Randy Rettberg for embodying the values upheld by synthetic biology and iGEM. The team also won a silver medal.

University of Oxford are also a gold medal-winners and took home the prize for the best diagnostics project.

You can read more about their projects on the Twist Bioscience Blog.

Cover image: The iGEM trophy for the grand prize winning high school team. Source: Flickr. Author: igemhq. Image licensed under CC by 2.0