Researchers build a toolbox for synthetic biology
For about a dozen years, synthetic biologists have been working on ways to design genetic circuits to perform novel functions such as manufacturing new drugs, producing fuel or even programming the suicide of cancer cells.
Achieving these complex functions requires controlling many genetic and cellular components, including not only genes but also the regulatory proteins that turn them on and off. In a living cell, proteins called transcription factors often regulate that process.
So far, most researchers have designed their synthetic circuits using transcription factors found in bacteria. However, these don’t always translate well to nonbacterial cells and can be a challenge to scale, making it harder to create complex circuits, says Timothy Lu, assistant professor of electrical engineering and computer science and a member of MIT’s Research Laboratory of Electronics.
Lu and his colleagues at Boston University (BU), Harvard Medical School and Massachusetts General Hospital (MGH) have now come up with a new method to design transcription factors for nonbacterial cells (in this case, yeast cells). Their initial library of 19 new transcription factors should help overcome the existing bottleneck that has limited synthetic biology applications, Lu says.
The project is part of a larger, ongoing effort to develop genetic “parts” that can be assembled into circuits to achieve specific functions. Through this endeavor, Lu and his colleagues hope to make it easier to develop circuits that do exactly what a researcher wants.
“If you look at a parts registry, a lot of these parts come from a hodgepodge of different organisms. You put them together into your organism of choice and hope that it works,” says Lu, corresponding author of a paper describing the new transcription factor design technique in the Aug. 3 issue of the journal Cell.
Lead authors of the paper include Ahmad Khalil, assistant professor of biomedical engineering at BU, Lu, and BU postdoc Caleb Bashor. Other authors are Harvard grad student Cherie Ramirez; BU research assistant Nora Pyenson; Keith Joung, associate chief of pathology for research at MGH; and James Collins, BU professor of biomedical engineering.