Finding better ways to produce clean energy, fight infection, attack cancer
By Sara Rimer, BU Research
Imagine the state-of-the-art 21st-century life sciences and engineering lab. It would bring together forward-thinking researchers from the hottest fields in bioengineering. These scientists would combine genomic technologies like DNA sequencing and synthesis, 3-D printers, and robots to make new molecules, tissues, and entire organisms. They would tinker in pursuit of cutting-edge questions like these: How do you guide cells to regenerate and build new tissue? How do you reprogram bacteria to fight infection—or reengineer the body’s immune system to attack tumors so they disappear? How do you organize the circuitry inside a cell so it sends all the right signals for optimal health?
This is the lab that Christopher Chen (BME, MSE), a College of Engineering Distinguished Professor and one of the world’s leading experts in tissue engineering and regenerative medicine, began dreaming up last summer with three ENG faculty who are young stars in synthetic biology—Ahmad (Mo) Khalil, Douglas Densmore, and Wilson W. Wong.
Now this dream is on its way to becoming a reality. The University is launching the new Biological Design Center (BioDesign Center), with Chen as the director and Khalil, an ENG biomedical engineering assistant professor and an Innovation Career Development Professor, as associate director. The other two core faculty members at the outset will be Densmore, an ENG electrical and computer engineering assistant professor and a Junior Faculty Fellow with the Hariri Institute for Computing and Computational Science & Engineering, and Wong, an ENG biomedical engineering assistant professor and a recipient of a National Institutes of Health Director’s New Innovator Award.
Through advances in genomics and stem cell research, many of the molecular and cellular building blocks of life have been cataloged. A central challenge is to understand, control, and reengineer how these component parts fit together to bring about functional biological systems that define life and solve important societal problems, ranging from producing clean energy to fighting infection and attacking cancer. That is the fundamental quest that brought Chen, Khalil, Densmore, and Wong together and that will drive the new center.
“Unlocking the underlying design logic of biological systems will revolutionize our approach to medicine, energy, and the environment,” Chen says, describing their shared vision. “Spanning synthetic biology, cell and tissue assembly, and systems biology, the Biological Design Center is positioned to lead this revolution.”
Up until now, he says, fields such as synthetic biology and tissue engineering have arisen as separate disciplines. Synthetic biology involves designing and synthesizing genes, genetic and signaling networks, and genomes to predictably control cellular behavior. Tissue engineering involves trying to manipulate and combine cells and extracellular materials to induce the assembly of tissues.
“But we realized that even though these two fields may involve slightly different tools,” Chen says, “they belong under one roof.”
Kenneth R. Lutchen, dean of ENG, was immediately excited about the possibilities when Chen broached the group’s idea.
“This is a unique approach to using engineering principles to understand and exploit biology,” Lutchen says. “Very few people are using bioengineering techniques and methods to help discover fundamental principles that govern how biological systems work, especially on multiple levels, from the gene level up to multiple organs.”
Chen, who earned an MD at Harvard Medical School and a PhD at the Harvard-MIT Division of Health Sciences and Technology, arrived at BU in 2013 from the University of Pennsylvania, where he was the founding director of the Center for Engineering Cells and Regeneration. Khalil, Densmore, and Wong had all been recruited to the University a few years earlier and were already collaborating.
“Chris is a very dynamic, visionary engineering scientist who is highly respected throughout the biomedical engineering community,” Lutchen says. “He brings a very deep sense of how to connect visionary research to medical and clinical questions. He has the depth and breadth of understanding the engineering challenges, the biological challenges, and the medical challenges as well as a sense of how things are connected between the gene level and the synthetic and systems biology level up to the level of multiple organ systems.”
Creating a community with no walls
Chen and his core faculty members will begin working together out of their existing labs in nearby buildings along Cummington Mall until they can move the BioDesign Center into laboratory space on several floors at what will be the Center for Integrated Life Sciences and Engineering (CILSE) building. Construction on the 610 Commonwealth Avenue building will begin late this spring and is expected to be completed within two years. Four to six new researchers—all exceptional innovators, says Chen—will be added to the center’s faculty over the next several years.
Housing the group at the CILSE, says Gloria Waters, University vice president and associate provost for research, “is a prime example of the goals of the new building—bringing together great scientists from different fields and breaking down the barriers to collaboration.”
Chen’s work spans tissue engineering and mechanobiology, which combines engineering and biology to study how physical forces and changes in cell or tissue mechanics affect development, physiology, and disease. He is a pioneer in the use of 3-D printing to help create organs using a patient’s own cells.
“One of the areas I’m interested in is regeneration,” Chen says. “How do you get cells not to go down the path of inflammation or dying or pathologic response? How do you guide them to go into a regenerative response where they might heal tissue?”
Khalil’s research involves using synthetic biology to understand and engineer genetic circuits that govern important cellular decisions and behaviors. Densmore, who is a Kern Faculty Fellow and the director of the Cross-Disciplinary Integration of Design Automation Research group, automates the specification, design, assembly, and verification of synthetic biological systems using techniques from computer design and manufacturing. Wong’s research focuses on ways to reprogram the body’s immune system to target and kill tumors.
The idea for the center was born when Chen, Khalil, Densmore, and Wong got together over a working lunch early last summer. The chemistry among the group flowed.
“We were talking about what kind of science we each want to do,” Chen says. “We realized how much commonality we shared in terms of the general concept of trying to understand how biological systems operate through the process of trying to control them. We just developed different kinds of tools to manipulate these systems. At that point we realized we should be working in one space rather than doing things separately.”
“It was clear to me, within a few minutes of speaking to Chris,” says Khalil, “that he fundamentally shares the synthetic biology philosophy, which is a desire to understand the rules of building complex and functional biological systems, regardless of whether one uses molecular parts, cellular components, or other raw biological materials.”
To achieve their vision, the BioDesign Center will mix and match researchers from multiple academic fields, undergraduates, graduate students, and innovators from industry. Their lab will have no walls. They will create a community, sharing tools, resources, and ideas with scientists across the University and beyond. They will invent, discover, experiment.
“The idea of tinkering is key,” Khalil says.
They want the center to be a leader in reinventing biological education, engaging students by framing concepts around understanding the logic of how things work. And they want students to learn through hands-on work—by making things and doing things in the lab.
“Classically, biology in high schools and colleges is often taught as a facts-based field,” says Chen. “We think that being able to actively tinker with a biological system—for example, making cells do things they weren’t intended to do—is how one learns more deeply about how these systems work. And the process of being able to do an experiment to see if an idea makes sense is part of the learning cycle for us as scientists, but also for students. The center will be a place where that cycle will be fostered amongst students as well as researchers.”
Khalil says he views the BioDesign Center as an experiment and an opportunity to shape the future of synthetic biology. For all its excitement and vast potential, he says, “if this discipline looks largely the same in five years, then it will have been a failure.”
It is his opinion, he says, that “we will have succeeded when this engineering approach to biology is adopted by all life science researchers—both to understand living systems and to exploit biology as a new technology for addressing societal problems.”
A version of this article originally appeared on the BU Research website.