Teams from TU Delft and Eindhoven have achieved successes in an international competition around synthetic biology. The Eindhoven team bagged a nomination in the 'Best New Application Project' category, while TU Delft walked away with the overall 'Grand Prize'.
The Delft team scored very highly with their idea for a method to demonstrate antibiotic resistance in bacteria in dairy cattle quickly and on the spot. This may allow the farmer to adjust treatment (in the case of resistant bacteria) and reduce unnecessary antibiotic use.
CRISPR
The students focused their idea on use in the dairy industry and a common disease in cows, namely mastitis (inflammation of the udder). The method uses a protein, Cas13a, which is part of the CRISPR-Cas family. The Cas13a protein is programmable to look for genes known to be specifically found in antibiotic-resistant bacteria. But unlike the other Cas proteins, once activated, the Cas13a protein then attacks all the other RNA in a cell. The Delft iGEM team has developed a test method to make this enormous RNA degradation visible. 'When detected, the turbid sample becomes clear and you can see that clearly with the naked eye,' says one of the students.
Keeping long
The students also thought about usability. In doing so, they collaborated with various stakeholders. 'To make more impact with our method, farmers should be able to detect antibiotic resistance in the field, without laboratory supplies.'
The students were inspired by a remarkable minuscule animal, the bear animal. Bear animals are considered the most resilient animals on earth. Shrivelling up allows them to survive in extreme conditions. When the bear critters come back in contact with water, they become active again a few hours later. The students figured out whether they could use specific proteins for bear critters to dry out the Cas proteins without losing their activity.
Proof of concept
Even though the students have proven in the lab that their method works, there is no product yet. "It is a proof of concept, so there is still a lot of optimisation to be done. Of course, we hope that companies will start working with our ideas and that a concrete application will come soon," says Aafke van Aalst. The detection method can be widely used to demonstrate resistance and make treatment strategies with antibiotics more efficient.
Tumour gel
TU Eindhoven received a gold medal and nomination for their project GUPPI, in which they propose encapsulating tumours in a gel to prevent them from growing and spreading further.
For GUPPI (Gelation Using Protein Protein Interactions), the team was inspired by the recent discovery of so-called membrane-less organelles. Organelles - as it were the organs of the cell - are normally separated from rest of the cell by a membrane, she explains, but there are also organelles that have no membrane around them.
'Those membrane-less organelles are formed by proteins that cluster together, just like in the gel we designed. To this end, we have modified so-called 14-3-3 proteins, on which they do a lot of research in our supervisor Luc Brunsveld's group, in such a way that they do not have two sites where other molecules can bind, but four. If you add to that the right binding partner, another protein we made ourselves, a gel is created.'
Tumours
The idea is that such a gel would only be formed near the tumour, as the gel formation is triggered by substances - proteases - secreted by that tumour. 'As a result, with this method you could encapsulate cancer cells and thus prevent them from growing further or spreading.'
This could potentially lead to a whole new way of fighting cancer, explains Vleugels. 'Existing therapies try to prevent the formation of those proteases, while our concept actually uses them.'
A real therapy based on GUPPI is not yet a reality for now, but the principle could potentially help visualise tumours. 'We visited an oncological surgeon at the Catharina Hospital and he told us that it is very difficult to visualise tumours in the abdominal wall. Because our gel also contains fluorescent proteins, he did see an application there.'
Hundreds of teams
International Genetically Engineered Machine (iGEM) is a competition for (student) teams using techniques from synthetic biology to solve a variety of problems. The final, or Giant Jamboree, is held every year in Boston.
During the several-day competition, some 300 student teams from all over the world were allowed to explain their ideas in presentations and poster sessions, after which it was announced whether they were good for a nomination - or even a prize - in one of the many award categories.
By: Kelly Bakker
Source: TU Eindhoven/TU Delft/iGem
