How Can Synthetic Biology Help Us Grow?

The story of the 2018 Makerere Uganda iGEM Team

By Jordan Villanueva

The iGEM team from Makerere University in Uganda faced seemingly insurmountable challenges in their research on plastic degradation. They had little previous lab experience and their university lacked the supplies and infrastructure to support their project. Even with sponsorships from Promega and several other biotechnology companies, they struggled to gather the funding necessary to get through the competition. Nonetheless, when I met team leader Alex Kyabarongo, he was optimistic about the future of synthetic biology research in Uganda.

“We want to extend this to the community,” Alex told me during the iGEM Giant Jamboree. “We want to remove the negativity around bacteria and tell people, ‘Look! There are bacteria that are deadly, and bacteria that are helpful. How can they be helpful?’ And I believe we have managed to establish our roots.”

An Invaluable Opportunity

Uganda is far from an epicenter of scientific research. According to the most recent data I could find, Uganda spent $280M on research and development projects in 2010, only 0.48% of its GDP. In contrast, the United States spends approximately 2.744% of its GDP. Bureaucracy and allegations of corruption within the government and educational institutions make it difficult for researchers to secure international funding. I was surprised to find that the website for Makerere University actually lists “contributions from graduate and undergraduate students” as one of its four main sources of research funding.

Besides the problems with funding, Ugandan students constantly struggle to find the resources they need for their research. Decades of minimal emphasis on public science education have left the country with a deficit of instructors. For many of the same reasons that international funding is throttled, few biotechnology companies have branch offices or distributors in the region, which hinders access to supplies and reagents. While students in wealthier countries often enjoy fully-stocked labs with reliable equipment, Ugandan students basically start from nothing with every research opportunity.

Makerere Uganda iGEM Team

The Makerere University iGEM Team was made up of 15 undergraduate students (13 pictured) and instructor Otim Geoffery. 

Photo provided by Alex Kyabarongo

When Makerere University Masters student Otim Geoffery heard about iGEM, he saw it as an invaluable opportunity to give more Ugandan students the chance to experience cutting-edge scientific research. iGEM, or the International Genetically Engineered Machine Competition, challenges students to use synthetic biology to address a problem they see in the world. Teams propose a project in the spring, spend the summer conducting experiments and gathering data, and present their accomplishments at the Giant Jamboree in the fall.

The organization has made slow progress in recruiting teams from Africa. According to the “Previous Competitions” page on the iGEM website, nearly 2,500 teams have competed since 2005, but only ten of those represented the entire continent of Africa. When Otim founded the Makerere University team in early 2018, it was the first team from Uganda and only the second African team from outside of Egypt or South Africa.

"...As a student, I see it as a dream..."

Otim designated himself as the team’s instructor and recruited fifteen students to participate. Most of the team studied either Veterinary Medicine or Biomedical Laboratory Technology. At the team’s first meeting, third-year veterinary medicine student Alex Kyabarongo was elected Team Leader. (“He is a genius,” Otim later declared.)

“We learn theory but gain little practice,” Alex told me, “So for me, as a student, I see it as a dream to practice this and to look for challenges and solve them. The biggest problem in Uganda right now is plastic disposal. People handle plastics with combustion, and we are looking at how we can degrade the plastic without burning it.”

In their project proposal, Alex and his team described plans to engineer E. coli with two genes from Ideonella sakaiensis, a bacterium that was shown in 2016 to digest polyethylene terephthalate (PET) plastic. PET is one of the primary pollutants in Uganda, often in the form of bottles and other consumer materials. The pair of enzymes Alex’s team identified is sufficient for hydrolyzing PET into its two environmentally safe monomers, terephthalic acid and ethylene glycol. The team believed that their project would result in a cheap, hassle-free method of dealing with the large amounts of plastic polluting their country.

Struggling to Make Progress

Makerere Uganda iGEM Promega

Alex Kyabarongo (center) meets Promega representatives Chris D'Jamoos (left) and Jenny Loeb (right) at the 2018 iGEM Giant Jamboree.

Once the team decided on a project, they faced an enormous financial shortfall. Before they could think about buying supplies and reagents, they needed $5,000 for registration fees. They reached out to potential sponsors on Twitter, including biotechnology companies, Ugandan media organizations, Floyd Mayweather and Donald Trump. While the undefeated boxer and the President of the United States never responded to their requests, Promega sent back a reply encouraging the team to apply for the Promega iGEM Grant. They submitted a project abstract, which later earned them $2,000 in free Promega products. They used most of this money on basic supplies such as agarose, barrier tips, ethidium bromide, DNA ladders, TAE buffer and competent cells.

“The Makerere Uganda iGEM team’s sponsorship application stood out because of its creative solution to solve the problem,” said Jenny Loeb, who leads Promega’s iGEM initiative. “They demonstrated that they had done their homework on this topic, and that made this team an easy selection for the review team.”

As they scrambled to raise the funds necessary for registration, equipment, reagents and travel, the team turned some of their attention to public outreach. They met with Kampala officials to discuss the plastic waste problem and determine the feasibility of their solution. They presented their plans to representatives from the Uganda Industrial Research Institution and the National Environmental Management Authority, both of whom instructed the team to return when the project was further along to discuss how the organizations could support commercialization and implementation of the system. At Makerere University, the team participated in multiple conferences and organized weekly seminars to explain synthetic biology topics to other students.

Unfortunately, the team struggled to make progress in the lab work. Few of the team members had any prior lab experience, and they were often held up by broken or missing lab equipment. They reached out to other teams on Twitter asking for help, and eventually set up Skype sessions with teams representing at least four different countries. According to the Makerere wiki, these conversations were productive for planning lab work, learning how to use equipment and navigating the complex requirements and deadlines associated with the iGEM competition. I later learned from other teams that the Makerere team would often end up giving more help than they received, usually by supporting other teams' projects with epidemiological or sociological research that was infeasible for teams outside of Uganda. 

The team began cloning their genes on August 20, several months later than most teams begin experiments. They still lacked some of the necessary supplies, but they had assembled as much as it seemed they could. By late September, they were analyzing E. coli cultures to search for PETase and MHETase expression, but their cells didn’t seem to be producing the proteins. With only a month to go before the competition, the team began evaluating every step of the process.

“A lot of brainstorming, a lot of troubleshooting, asking, ‘Why is it not expressing as well as we want?’” Alex said. “We were getting results, just not very good results. We finally found what it was—most of the gene was wrong.”

Alex didn’t disclose many details about the issues, but he told me that an unnoticed error in one of their orders from another biotechnology company had derailed their experiments and left them with results far from what they were hoping for. He also mentioned that he was talking to a representative from the company to figure out how the order could be corrected so that the team could continue their project after iGEM ended.

When the deadline for adding information to their wiki page on the iGEM website arrived, the Makerere team had little data to report. In lieu of concrete results, they posted background information about pollution in Uganda and details about their collaborations and outreach. Having only raised enough money to send one team member to the Giant Jamboree, the team decided to send Alex to represent them in Boston.

And so, in late October 2018, Alex Kyabarongo left Uganda for the first time in his life, alone, to travel over 28 hours to Boston, Massachusetts.

Makerere Uganda iGEM Alex Sign

Alex poses with the iGEM sign at the 2018 Giant Jamboree.

Photo provided by Alex Kyabarongo

Scientific Utopia

The iGEM Giant Jamboree is the culmination of the iGEM competition, when thousands of students gather to give presentations and poster talks, meet collaborators around the world, and, hopefully, receive awards. I’ve described it before as “scientific utopia” – everywhere you look, students are excitedly discussing synthetic biology. At the Giant Jamboree, science transcends borders and politics. Open science isn’t just encouraged, it’s the norm. There, relationships are fostered that could usher in the next major discoveries in biology.

I caught up with Alex on Wednesday evening, the night before the Opening Ceremonies.

“This is my first time in the United States, and even my first time on a flight,” Alex told me. I asked if he had any sightseeing plans while he was in Boston. “If I can; if I have time. Maybe I can get someone to help. There is a doctor from New York who I have talked to, and she told me she is going to look for me.”

I had been following the Makerere team’s progress on their wiki, so I was somewhat aware of how little data Alex had to present. I asked Alex about his goals for the weekend.

“I call it a success already because we are here,” he said, “But we want to see our project win that medal, and I believe that it will.”

"We did our best, and I know that next time we come, we will be better."

When the Jamboree started, Alex was in the middle of everything that was happening. He connected with collaborators and teams he’d communicated with on social media. I saw him networking with representatives from biotechnology companies and instructors from prestigious universities. He brought a natural charm to every conversation, sparking smiles and laughter from everyone. By the end of the first day, every time I saw him, he was introducing me to a new friend he thought I’d like to meet.

Alex was scheduled to give his presentation to the judges at 10:00am on the second day of the Jamboree. I got to the conference room half an hour early, and Alex was already inside, practicing his slides one last time. He was dressed in a pale-yellow polo shirt with his team’s logo embroidered on the chest. No one else in the room bothered him or even sat next to him, respecting his last-minute cramming. He stared intently at his screen, oblivious to the presentations going on around him. As it approached 10:00, dozens of other iGEM participants streamed into the room. By the time Alex stepped on stage, almost every seat in the room was taken.

Makerere Uganda iGEM Presentation

Alex presents his project to a room packed with iGEM judges, participants and instructors.

Photo provided by Alex Kyabarongo

Makerere Uganda iGEM Poster Judge

Alex explains his poster to a judge several hours after his presentation.

“Good morning to you all,” Alex began, speaking to a crowd of over fifty. “This is the iGEM team from Makerere University in Uganda, in East Africa. This is our first time presenting to iGEM. You see me here, alone, but my whole team contributed to the same cause.”

In the next sixteen minutes, Alex painted a vivid picture of his university struggling from a lack of resources, his city drowning under mountains of plastic, and his team fighting to succeed in iGEM. He talked about the disadvantages East African scientists face without easy access to the tools of research, and the uphill battle to convince an overwhelmingly skeptical community that bacteria can, in fact, be helpful. He showed pictures of his teammates meeting with politicians, government officials, scientists and other students at Makerere University. Alex never attempted to mask his lack of data, rather, he thoroughly explained his team’s shortcomings and detailed their plans to continue the project after the Jamboree.  He concluded by thanking the team’s sponsors and giving shoutouts to several collaborators in the audience.

“In the coming years, I want to see us expand our team,” Alex told the judges. “Our team was mostly composed of veterinarians who had little knowledge about biotechnology. But we did our best, and I know that next time we come, we will be better.”

When the presentation and Q&A ended, the applause was deafening. Immediately afterwards, over two dozen people lined up in front of the podium where Alex was standing. As I listened from nearby, I realized they weren’t questioning him on the project or his lack of data. Many of them just wanted to shake his hand, congratulate him, and offer any support the team needed to continue their research and return to iGEM in 2019. Alex greeted most of them like old friends, including representatives from collaborators and sponsors.

“He did well – he did really well!” Hamburg team member Bjarne Klopprogge told me afterwards. “I worked on the collaboration with iGEM Makerere for our team. They really helped us develop our project working on malaria. They told us personal stories, distributed our questionnaire in Uganda, connected us with epidemiologists and people in the lab, and this way we got a lot of input.”

“We hope we helped them a bit, but they definitely did much more for us than we did for them,” said Daniel Wedemeyer, another member of the Hamburg team.

"This is just the beginning"

The Makerere team didn’t win a medal as Alex had hoped, nor did they receive any of the special track awards they had applied for, including Human Practices and Public Engagement. What they did accomplish, however, was building a strong case for investment in Ugandan biological research. Besides their domestic success through conversations with politicians and other scientists, Alex used the Jamboree to forge relationships that he hopes to leverage for future collaboration. By the end of the week, nearly everyone I talked to mentioned meeting “Alex from Uganda.” I watched Alex get high-fives from entire teams, and instructors go out of their way to greet him. Everyone smiled as they recounted their conversations with him, and many said they’re excited to see what the Makerere team accomplishes in the future.

"Meeting Alex was one of the many highlights of the 2018 Jamboree!" Jenny Loeb told me a few weeks later. "Alex effectively brings awareness to the struggles that he and his teammates, and Ugandan researchers in general, face in trying to conduct their research. He is also truly passionate about science and using synthetic biology to solve serious local and global problems."

The Makerere iGEM team exemplified many of the principles valued by the iGEM foundation and scientists around the world: collaboration, open communication, teamwork and friendly competition. They overcame unique challenges and achieved unprecedented recognition on the global stage. Though the iGEM season didn’t have the outcome he’d hoped for, Alex remains dedicated to his goal of bringing cutting-edge biology to Uganda. More than anything, he reminded me that science can—and should—be used to solve the problems we see in our own communities.

“We see synthetic biology and ask, ‘how can it help us grow?’” he told me. “This is just the beginning of how synthetic biology can help solve the challenges for humans, animals, and living in the environment.”

If this is the beginning for Alex, I can’t wait to see what comes next.

Makerere Uganda iGEM Alex

Alex left an amazing impression on everyone he interacted with at the Jamboree. We can't wait to see what he and his team accomplish next. 

Photo provided by Alex Kyabarongo