Each year since 1951, a group of Nobel Laureates gather in Lindau, Germany to meet the next generation of scientists from around the world. At this year’s 68th Lindau Meeting, 39 Nobel Laureates met with 600 undergraduates, Ph.D. students and post-doc researchers from 84 countries to foster the exchange of new ideas and breakthroughs among scientists.
Among the many scientific leaders attending this year’s event were Helge Bastian, Thermo Fisher Scientific’s vice president and general manager of synthetic biology, and Mary Ann Santos, senior technical sales specialist for synthetic biology. Helge and Mary Ann attended as official delegates to present on Thermo Fisher’s role in a multi-organization collaboration to solve a global food safety challenge: ridding the world’s grain supplies of aflatoxin.
Aflatoxin is a naturally occurring poison released by mold and a serious health concern in developing countries. Four and a half billion people are exposed to aflatoxin every day, putting them at risk of developing health conditions such as liver cancer. Last October, Mars, the global maker of confectionery, food, drinks and pet care, the University of California, Davis, the University of Washington, Northeastern University, the Partnership for Aflatoxin Control in Africa and Thermo Fisher kicked off a unique collaboration to use a computer game called Foldit to crowdsource new methods to neutralize the poison.
How does the game work? Players log in to Foldit where they attempt to restructure a protein enzyme that can be used to destroy aflatoxin. Since it launched, more than 1,000 gamers worldwide have participated in the first two rounds of the challenge, designing more than 1 million enzyme structures. Of those, UC Davis so far has selected 222 of the most promising designs for Thermo Fisher to synthesize for further testing to determine their real-world potential to degrade the toxin.
“Thermo Fisher has committed to contributing our proprietary gene synthesis services to this corporate social responsibility project as part of our mission to enable our customers to make the world healthier, cleaner and safer,” said Bastian. “We’re trying to solve a major and long-standing real-world problem, but our approach to finding a solution is a little bit science fiction. We’re pushing past the edge of what’s possible today, and that is extremely fascinating for many scientists.” Bastian added, “We’re honored to have been invited to attend the Lindau Nobel Laureate Meeting to present on the latest results from the aflatoxin project. It was a tremendous opportunity to inspire the next generation of scientific minds and reimagine what is theoretically possible when cost and time are no longer prohibiting factors for synthesizing DNA at scale.”
The lab team at UC Davis is optimistic that each round of the game is bringing them closer to finding an enzyme that could be used to destroy aflatoxin.
According to Justin Siegel, associate professor of chemistry and biochemistry at UC Davis, “In the first round, the gamers were able to make mutations as well as introduce insertions or deletions into the protein and we directly generated DNA-encoding player designs. Unfortunately, none of the proteins produced were viable for testing against aflatoxin. In the second round we refined the design parameters based on the players’ data and were excited to find that one-third of the designs became viable for testing for aflatoxin activity. The enriched function of the protein from round one to round two is an encouraging sign; we hope to utilize this information and further refine design parameters to generate as many viable designs as possible to improve the odds that we will be able to synthesize a protein that can end this global health crisis.”
Over the first two rounds, UC Davis has succeeded in condensing the design-to-data cycle from 10 weeks to closer to six, an impressive turnaround time that demonstrates the potential for applying the design, build and test cycle to future synthetic biology initiatives.
“This is a new approach to extending the function of a protein,” said Michael Liss, senior manager for research and development at Thermo Fisher. “Essentially, we are trying to deduce the protein’s function based on data from its amino acid sequence. Due to the complexity of folding into a specific three-dimensional structure, it’s basically the equivalent of trying to predict the weather three weeks from now down to the exact temperature at a specific time of day. No matter how much data we have, it’s impossible to make an accurate prediction. By enlisting hundreds of gamers in finding a solution, however, we increase the chances of success astronomically.”