Manipal BioMachines, an iGEM 2020 team, is engineering bacteria to decrease mercury toxicity for humans

Manipal BioMachines is a group of students in India who are using synthetic biology to find a solution to methylmercury poisoning. Exposure to mercury, a powerful neurotoxin, can cause serious health problems, and it most commonly occurs when people eat kinds of fish and shellfish that have high levels of methylmercury in their tissues.

The students are representing the Manipal Institute of Technology at the International Genetically Engineered Machine (iGEM), a synthetic biology competition that brings together young people from more than 40 countries.

The team recently joined the iGEM program on Just One Giant Lab (JOGL), a platform that is fostering open collaboration between iGEM teams working on the Sustainable Development Goals.

To learn more about the project, called Breaking Bond, we interviewed the team members by email.

Can you tell us about your project? Why is your research important?

Soumodeep Sarkar, Head of Research:

Approximately 3 billion people in the world rely on wild-caught and farmed seafood as a primary source of protein, and fish now accounts for almost 17% of the global population’s intake of protein. As it is one of the world’s primary sources of food, any drastic changes to the population or nutritional value of fish can have a considerable impact on human health.

For example, when people eat fish that contain methylmercury, an organic compound that bioaccumulates in some fish, it can cause serious health problems and toxic effects on the nervous, digestive and immune systems, and on kidneys, lungs, skin and eyes. Human activity, such as coal burning, is the main cause of mercury releases, and this element is also found in products such as batteries, thermometers, electric switches, and lamps.

The problem of mercury pollution starts when mercury released into the environment is converted into methylmercury by microorganisms like sulfur-reducing bacteria. These compounds are then absorbed by plankton and small fish. Large fish are more likely to contain high levels of mercury as a result of eating many smaller fish that have acquired mercury through the ingestion of plankton. This is called biomagnification.

Mercury poisoning has led to many disasters such as the 1971 Iraq poison grain disaster, and the Minamata Disease in Japan. The organic form of mercury (methylmercury) is more toxic than the inorganic form, and it’s believed that the global rise in temperatures is leading to increased levels of methylmercury in fish.

We at Manipal BioMachines will be genetically engineering a probiotic bacterium that converts methylmercury to elemental mercury, which is safer, has very low absorption in the gut and is mostly excreted by the body. We are hoping to develop a long-term and efficient solution to this problem of mercury toxicity. Our probiotic could be accessible to a large number of people around the world.

We hope that this project will be the beginning of an ongoing body of research into the issue of monitoring methylmercury poisoning and its health effects, such as its neurotoxicity and nephrotoxicity, embryotoxicity, and teratogenicity, mutagenicity and carcinogenicity.

How did your project get started? How did you become interested in this topic?

Lavanya Karinje, Wet Lab Member:

Our team leader, Varun Kumar, heard about the iGEM competition when he was in high school. When he joined our university, Manipal, one of India’s leading academic and research institutions, he noticed that there weren’t any biotechnology-based student projects here, so he decided to start a team to join not only iGEM, but other competitions and conferences as well. Given that this is the first student project working on biotechnology, we have received a lot of support from our professors and administration!

Our team came up with many different ideas, and narrowing them down to a single topic seemed almost impossible. Varun then suggested we could help tackle the problem of methylmercury poisoning. He had read that this issue was affecting the coastal town of Mangalore, where seafood is highly popular. The rest of the team was almost immediately on board, given that many people in our country consume seafood and rice (probable sources of methylmercury poisoning). We felt that it would be highly beneficial if we found an efficient solution to this problem.

What is the coolest thing about your project?

Adithi Somayaji, Wet Lab Member:

We are also looking at how we can avoid side-effects like methylmercury-induced inflammation. Our probiotic bacteria could release anti-inflammatory cytokines in the gut, in the presence of methylmercury, to reduce the effects of inflammation.

In case you want to know the technical details: the control mechanism for this is the SoxR- SoxS system, where SoxR is in the BioBrick containing the MerR- PmerT system, which activates only in the presence of mercury, in turn, activating SoxR only in such conditions. The SoxR then activates the SoxS promoter only in the presence of pro-inflammatory signals such as NO, ensuring that the anti-inflammatory cytokine is released only in the presence of methylmercury induced inflammation.

What kinds of challenges are you facing?

Niyati Sanghvi, Management Head:

Due to the COVID-19 pandemic situation, we are unable to access our lab and perform wet-lab experiments. We are also unable to visit our target demographic (the coastal rural regions where fish consumption is high) and learn about the intricacies of these communities. However, this has also allowed us to innovate and think out of the box to analyze our project in the best way possible.

What are your next steps? What do you want to achieve with your research?

Varun Kumar, Team Leader:

Due to the impact of the pandemic, we decided to divide our project into two phases. We are currently working on designing parts and experiments to build a probiotic that serves as a long-lasting and efficient solution to methylmercury poisoning, which can be made accessible to a large number of people, in terms of cost as well as usability.

Although our primary aim is to provide proof-of-concept, we are also developing the entire process for the production of these capsules. Right now, we are using the data that’s already available in the literature. The second phase, taking place next year, includes performing experiments in the lab and planning the next steps when we get the results.

What actions can other iGEM teams take this year in order to achieve some of the SDGs?

Soumodeep Sarkar, Head of Research:

iGEM teams can analyze their projects and think about which of the SDGs they can contribute to. They can also hold discussions and debates to share different perspectives, which can help not only in identifying these unique problems but also coming up with inventive solutions.

In collaboration with The Dais India, EMERGE, BITSMUN Goa, and iGEM BITS Goa, we organized the first-ever national-level iGEM India BIOSUMMIT 2020 on July 25th. This was part of the All India iGEM Meet which was conducted July 31 — August 1. Our goal was to lead a healthy discussion revolving around the SDGs. We had four committees: Ethics of Terraforming, Medical Data Privacy, Prevention of Biowarfare, and Genetic Cosmetic Treatments.

Each committee had a fruitful discussion about their respective agendas, and the judges and moderators gave interesting insights and ensured the smooth flow of the event. At the end of the discussion, the panel for each committee announced a ‘Special Mention’ which was given to one of the members, along with an exciting ₹1.5K cash prize.

Note: learn more about how to join the iGEM program on JOGL, check out the video below.