Probing and Reprogramming Life
BU Holds First Annual Synthetic Biology Boston Conference
By Mark Dwortzan
Synthetic biologists conceive, design and build molecular biological systems that rewire and reprogram living cells and organisms to perform specified tasks, all to improve our understanding of biology and solve critical problems in healthcare, energy and the environment, food safety, global security and other domains. Recognizing the vast potential of synthetic biology and trailblazing efforts of its faculty, the College of Engineering launched the Boston University Center of Synthetic Biology (CoSBi) last fall to advance this emerging discipline.
CoSBi’s core faculty—Professor James Collins (BME, MSE, SE), who directs the center, and Assistant Professors Douglas Densmore (ECE, BME, Bioinformatics), Ahmad “Mo” Khalil (BME, Bioinformatics) and Wilson Wong (BME)—are some of the foremost leaders in the field, placing BU among the nation’s preeminent synthetic biology institutions, which are largely based in the San Francisco Bay Area and Greater Boston.
To bring together Boston and Cambridge-based researchers in the field, CoSBi held its first annual Synthetic Biology Boston (SB2) conference on June 9 at the BU Photonics Center.
Participants at the one-day workshop included experts from a variety of life sciences and engineering disciplines, software developers from academic and industrial labs, and regional industrial and startup company representatives. SB2 focused on leading edge research that’s advancing and harnessing synthetic biology approaches, and sought to foster new collaborations and partnerships among academic and industrial researchers.
“With the genesis of CoSBi, we talked about creating a pivotal event that would bring together Boston-area researchers in synthetic biology, further strengthen what’s becoming a vibrant community here in Boston, showcase some of the novel synthetic biology approaches being developed and used, and highlight talks by world renowned researchers,” said Khalil, associate director of CoSBi.
SB2 featured two keynote speakers—the inaugural Charles Cantor Lecturer, Jack W. Szostak, 2009 Nobel Laureate in Physiology or Medicine, and stem cell biologist George Daly—along with 12 15-minute talks delivered by graduate students and postdocs representing established synthetic biology labs in the Boston area. More than four hours were set aside for discussion, much of it beside 27 research posters prepared specially for the event.
“Unlike most symposia, where the PIs give talk after talk, we’ve flipped the format so that the majority of the events allow for networking and interacting rather than sitting and listening,” said Khalil. Priming the pump for such conversations were the 12 short talks on research developments emerging from labs at BU, MIT and Harvard.
Noting that the design and construction of genetic circuits are limited by the availability of biomolecular parts, Clement T. Y. Chan described how the Collins Lab is combining different functional domains from a family of proteins to produce synthetic transcription factors, or proteins that turn genes on and off. These engineered transcription factors can be incorporated into a wide range of genetic circuits that empower cells to perform specific tasks.
Ernst Oberortner highlighted software tools developed in the Densmore Lab which draw on concepts from electronic design automation to automate the specification, design and assembly of engineered biological systems. Oberortner also introduced a Computer Aided Design (CAD) framework that Densmore has advanced for creating microfluidic devices for use in synthetic biology, in collaboration with Khalil.
Albert J. Keung explained how he and other members of the Khalil Lab are modifying and engineering a set of proteins that regulate chromatin, the packaged structure of DNA and proteins within a cell’s nucleus. These chromatin regulator (CR) proteins play a key role in activating and repressing genes throughout the cell, so altering their makeup could provide a new way to engineer the cell’s genetic circuits to perform desired functions.
Benjamin Weinberg presented a new method developed in the Wong Lab to produce synthetic genetic circuits in mammalian cells that can receive and transmit multiple signals, thus enabling many logical operations involved in reprogramming cell behavior. Weinberg’s poster on this research won the Best Poster award, garnering the most votes from conference participants.
MIT and Harvard
Focused on microfluidics technology for synthetic biology, David Kong described efforts at MIT Lincoln Laboratory to create a user-friendly, integrated system where users can assemble thousands of microfluidic genetic circuits in parallel, and a design repository where synthetic biologists can upload or access designs.
Representing MIT’s Synthetic Biology Center, Andras Gyorgy presented a framework developed in the Domitilla Del Vecchio Lab that could enable more reliable and predictable design of synthetic circuits composed of multiple genetic circuit modules; Allen Chan described research in the Timothy K. Lu Lab to engineer living functional materials that self-assemble and sense environmental cues; Irene Brockman explored how the Kristala L. J. Prather Lab is engineering bacteria to convert biomass to biofuels, biopolymers, pharmaceuticals and other valuable products; Bryan Der summarized the Voigt Lab’s work on Cello, software that automates the design of combinatorial logic circuits in bacteria; and Patrick Guye described efforts at the Ron Weiss Lab to reprogram stem cells to grow into specific tissues and organs.
Showcasing research at Harvard University and its Wyss Institute for Biologically Inspired Engineering, S. Jordan Kerns outlined how the Pamela Silver Lab is engineering E. coli and other microbes in the gut to detect and record biomarkers for gastrointestinal diseases; and Luvena Ong highlighted work by the Peng Yin Lab on the modular assembly of DNA nanostructures that can be exploited to probe or reprogram biological processes for imaging and therapeutic applications.
The inaugural Charles Cantor Lecturer, Nobel Laureate Jack W. Szostak, discussed his efforts to model how a simple cell might be synthesized from molecules, and thus shed light on the origin of life. He’s designing this “protocell” to self-assemble from its constituent molecules, encode heritable information, and embody mechanical and chemical energy for cell growth, division and other functioning. Szostak’s work could lead not only to new insights about the origins of life, but also new ideas for reengineering cells today.
A professor of chemistry and chemical biology at Harvard University, genetics at Harvard Medical School, and an Howard Hughes Medical Institute Investigator who has made seminal contributions to the field of genetics in his 30-year career, Szostak won the 2009 Nobel Prize in Physiology or Medicine for the discovery of telomeres, DNA sequences that protect the ends of chromosomes from degradation. His lecture was sponsored by Professor Emeritus Charles Cantor (BME, MED), a pioneer in synthetic biology who once directed the Human Genome Project and served as director of BU’s Center of Advanced Biotechnology, the forerunner of today’s Center of Synthetic Biology. Cantor attended the conference and announced the winning poster.
The biology keynote speaker, Boston Children’s Hospital/Harvard Medical School stem cell biologist George Daley, examined ways to engineer stem cells to grow bodily tissues and organs. In collaboration with the Collins Lab, Daley is developing a computational platform aimed at empowering synthetic biologists and other life scientists to engineer such tissues and organs for modeling disease, screening drugs and replacing defective body parts. The symposium also included an industry speaker, “organism engineer” Patrick Boyle, who described how Gingo BioWorks, an MIT spinoff that built the first facility for flexible, industrial-scale organism engineering, is applying standardization and high-throughput parallel processing to simplify and accelerate its operations to produce everything from flavor enhancers to perfumes.
“I’m excited to see this community come together,” said Densmore in closing. “This workshop shows that this community exists, that it’s diverse yet collaborative, experienced yet young and excitable. I take this as a charge to follow up on these collaborations and make some of the vision we saw today a reality. The best way to continue doing this fantastic work is to go forth and collaborate over cocktails at the reception!”