Synthetic Biology for Drug Discovery at the  Intersection of Teaching and Open Research

People involved: Jake Wintermute, Ariel Lindner, Nadine Bongaerts
 
Keywords: Tuberculosis, antibiotics, drug discovery, synthetic biology, citizen science
 
Project Description:
 
The need to discover new antibiotics is widely acknowledged. Commercial biotech companies, once leaders, are leaving the field as technically difficult and unprofitable. Public efforts must therefore take up the responsibility and open-science collaborations must be scaled up to match the global challenge. Fortunately, students and citizen scientists are eager to get involved, motivated by the potential to do good as they learn.
 
This project is about a new way to discover antibiotics and other medicines. We will take a safe, easy-to-grow lab bacterium and genetically modify it to express essential genes from a dangerous, hard-to-grow pathogen. The modified bacterium can then be used as a proxy to test for drugs that may kill the dangerous pathogen. Because there are many different genes to replace, and many different drugs to test, the technique could potentially scale to involve hundreds of labs and citizen scientists around the world.
 
This conceptually simple approach has only recently become possible due to advances in the field of synthetic biology. Next-generation inducible promoters and rationally designed expression cassettes allow gene dosage to be precisely controlled. Cheap DNA synthesis allows many designs to be tested in parallel, accelerating the design cycle. This project will challenge our ability to move genes between organisms in ways that are elegant, precise and non-perturbative.
 
Beyond our scientific goals, we will seek to activate, motivate and empower collaborators of all kinds. The work will seek to answer two questions at the intersection of science, eductation and human well-being.
 
First: How can we include the global public in biological research that is fundamentally hands-on? While lectures, quizzes and textbooks can be successfully communicated with digital media alone, real research requires free-form interaction and play. How can we provide an interactive experience in ways that scale?
 
Second: How can we align biotechnology to better serve the public good and earn the public trust? Drug development, as it is traditionally practiced by Big Pharma, is widely condemned as greedy and unaccountable. Synthetic biology, the technology of GMOs, is seen by many as unnatural and dangerous. When the two subjects are combined, the controversies multiply. We will need to abandon most of the established models and rebuild a process that is open, responsible, and inclusive.