Detecting chronic intestinal inflammation with a pill – Innovation Origins

In the Netherlands, around 90 thousand people have a chronic intestinal disease, such as Crohns disease. These inflammations are easy to detect. The only thing you need for that is an endoscopy: a camera that goes into the intestinal tract. Invasive and unpleasant, says Luke Rossen, team manager of the iGEM student team in Eindhoven. The team developed a method where gas bubbles from E.coli bacterium and an ultrasound machine reveal whether there is an infection and where it is located.

If you have an inflammation in your intestines, your body produces a substance, Rossen explains. That substance can bind with certain proteins which can trigger the production of gas bubbles. If you introduce these proteins into E.coli bacteria, then it acts as a kind of sensor. Those gas bubbles that then form can subsequently be visualised using ultrasound. That way, you can detect the inflammation with an ultrasound machine. All the patient has to do is take a pill containing the bacteria the day before.

The team is participating in the global iGEM competition, part of the International Genetically Engineered Machine (iGEM) Foundation with their discovery. An independent, non-profit organisation dedicated to the advancement of synthetic biology, the (re)design and construction of organisms or parts thereof. This year, 356 student teams from countries in Europe, Asia, North and South America and Australia are competing in the competition. Each year there is a Giant Jamboree, although this year a smaller version is being held digitally in Paris due to corona.

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It is also the case nowadays that people suffering from intestinal complaints first take a self-test, Rossen goes on to say. That test is not very specific. Even if there is nothing wrong, a person is sometimes still sent to hospital for an expensive invasive endoscopy examination. That person has to make sure their bowels are empty beforehand, so the day before, they have to take strong laxatives and fast. They are also given an anaesthetic during the treatment. A trained doctor and two nurses are present during an endoscopy. Whereas in almost 30 per cent of cases, this is not necessary.

The iGEM teams so-called IBDetection method falls somewhere between the self-test and the extensive follow-up examination. The students have modified the intestinal bacterium E. Coli so that it acts as a sensor. That implies cutting and pasting with DNA, says Rossen. Its like doing a puzzle with very small building blocks. We put some DNA and the bacterium together and examine what does and doesnt work. You take out a certain piece, see what the reaction is and keep going until you have the right reaction with those gas bubbles.

Actually, the biology textbooks of primary and secondary schools should be rewritten, Rossen states. Because working with so-called genetically modified organisms (GMOs) is still new, the team manager notes. You hardly ever learn anything about it in primary and secondary schools. In order to educate young people about genetic engineering, the team gives guest lectures. For example, we show them what soap does. You wash your hands every day, but what happens? Actually, it is just a molecule that binds water and fat. We want to explain the basic principles, which can also be applied to what we do. For instance, how a protein binds to a substance.

The team also came up with an escape room, escape the cell. You walk through parts of a cell in each room and have to solve a puzzle. That is how you learn what a cell looks like. A number of secondary schools are now making use of the escape room to try it out, Rossen adds.

On 21 October, the team uploaded everything from their cases, documentation, research and tests into a wiki. Like their research that they did in collaboration with a student team from Vienna that is developing something similar. The teams interviewed people with chronic inflammatory bowel disease about whether they would prefer an examination using an endoscopy or an ultrasound machine and swallow a pill. This revealed that people were sympathetic to our idea, says Rossen. Very different from what we had assumed beforehand. We thought people would be more negative about it because we are working with genetic manipulation.

In addition, the students participated in the RIVM Safe by Design competition to demonstrate that their method is safe. During the Sustainable Healthcare Challenge, the team finished in third place. The last test results were also a success: the team succeeded in inserting the definitive DNA into the bacteria.

After 21 October everything will be open to the public. Rossen: If you want to know exactly what we do, then it is in there. After that time, there will be a period of relative calm. It was a lot of hard work and then it was finished. To bridge the time until the Giant Jamboree, the iGEM team is organising a mini jamboree for the Benelux. Everything in miniature but with judges and a prize.

Rossen signed up for participation in the team at the end of last year. His professor sent all his students a call out to participate I had only just had a taste of some practical lessons when the lockdown started. I missed doing practical work. Being able to participate in this was a godsend. The masters student in Biomedical Engineering worked full time on the project from May. Once the competition is over, the team will hand over the baton to a new team.

If it all works out, the biggest challenge is to change legislation so that it can be put into practice, Rossen says. Thats lagging behind in Europe. He spoke to Lucie McMurtry of EuropaBio, about the European Legislation on Genetically Modified Organisms (GMOs). What is the future outlook? My reply was that there is not much chance of our concept being approved within the next ten years. Purely because we use living GMOs as sensors, regardless of whether it is safe or not. Rossen is convinced that research within synthetic biology makes sense. We want to use fundamental research to show that it is safe. It is a first step towards the future: there is potential in it, its not scary, as long as you think about it properly and thoroughly and test everything meticulously. Then its just like any other drug only a bit more complex.

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Detecting chronic intestinal inflammation with a pill - Innovation Origins