The National Science Foundation has awarded $24 million over five years for a new ‘blue-sky’ bioengineering center based at UC San Francisco. Known as the Center for Cellular Construction, the new initiative aims to transform the field of cell biology into a quantitative discipline and to adapt tools from engineering, the physical sciences, and computer science to design automated machines out of living cells.
“This is my lifelong dream,” said Wallace Marshall, PhD, a professor of biochemistry and biophysics at UCSF who will serve as director of the new center. Marshall says he has always looked for a way to combine his childhood loves of engineering and biology, citing a 1981 article in OMNI magazine which described fantastical biological computers: “The idea was that you could build computers and other machines using biological building blocks. That’s exactly what our new center will try to do.”
The Center for Cellular Construction grant is one of four new NSF Science and Technology Center awards announced Sept. 26, 2016. The center will be administered by UCSF, and includes researchers from San Francisco State University, Stanford University, UC Berkeley and IBM Research – Almaden. The IBM collaboration will bring IBM’s Watson artificial intelligence platform to bear on advancing synthetic biology. The center will also partner with the Exploratorium science museum in San Francisco and local high schools to bring excitement about synthetic biology to the general public.
“UCSF is home to a burgeoning synthetic biology movement, which grew out of the recognition – more than 15 years ago now – of the incredible value of using engineering approaches to unleash the power and utility of biological systems,” said Lim, a professor of cellular and molecular pharmacology in the UCSF School of Medicine and a Howard Hughes Medical Institute investigator. “With our strengths in cell biology, engineering and synthetic biology, UCSF is proud to host this new cutting edge interdisciplinary center, which would not have fit neatly within traditional department, school, or institutional boundaries. I believe this truly represents the future of biology.”
Researchers in the new center will collaborate to develop new scientific tools to allow scientists to reliably engineer cells for desired functions by modifying their internal organization; to design complex multicellular and multi-organism structures to accomplish specific tasks; and to develop living “bioreactors” that can generate products of commercial value such as drugs or biofuels.
“The notion of engineering biology is very different from what other engineers think about,” said Gartner, an associate professor of pharmaceutical chemistry in the UCSF School of Pharmacy. “It’s not chipping pieces off a block or snapping components together – biological systems are self-organizing, and that presents both a great challenge and an incredible opportunity.
“If we could engineer biology like we currently engineer cars or factories, the implications would be limitless,” Gartner said. “Imagine self-assembling materials, chemical plants that could adapt to process multiple different feedstocks or respond to changing environmental conditions, or medicines that could go after diseases in smart ways. What’s more, understanding the fundamentals of how cells change and adapt could give us better abilities to look at diseased tissues and figure out what’s going wrong based on how the cells are behaving.”
Five Projects the Center Will Focus On
The center will focus on five projects, ranging from basic research to real-world applications, integrated to permit the center to implement iterative “design-build-test” cycles in the development of living cellular machines:
The Cellular Machine Shop: The center will assemble a core facility full of cutting edge cell engineering tools, including high-throughput quantitative imaging systems, gene synthesis tools, and next generation sequencing machines to accelerate the rest of the center’s projects.
Computer Aided Design (CAD): Researchers aim to create a computational platform — modeled on the CAD software used by mechanical engineers — to aid researchers around the world in precisely and predictably designing cells and multicellular structures with desired functions based on knowledge of their inner workings.
Multicellular Engineering: The center will develop the molecular tools necessary to construct multicellular structures capable of executing complex functions using multiple specialized cell types or organisms as building blocks. (For instance, see the Gartner group’s recently developed “DNA Velcro”).
Living Bioreactor: Researchers will implement new approaches to engineering cells’ behavior and metabolic activity by modifying their internal structures and combining them with other cell-types and organisms.
For instance, companies that aim to use algae to turn sunlight into biofuels have struggled with low yields and interference from bacteria and other organisms that compete with the algae. Researchers at the new center hope to improve biofuel yields by tuning the size of organelles within the cells that store energy, and envision surrounding these boosted algal cells with tough fungal cells and other organisms that produce antimicrobial defenses or aid flotation, to produce self-assembling, self-healing units capable of withstanding harsh conditions, resisting contamination, and facilitating harvesting.
Cell State Inference Engine: The center will design image analysis software to enable researchers to use engineered cells as living sensors of environmental conditions — with real-world applications such as monitoring air pollution or serving as industrial quality control sensors. Collaborator Simone Bianco, PhD, a research staff member at IBM Research – Almaden will play a major part in applying IBM’s artificial intelligence expertise — including the IBM Watson machine learning platform — to this ‘canary in a coal-mine’ project.
"Our collaboration will produce an unprecedented amount of data,” said Bianco. “Using cells as sensors, we can develop cognitive maps that help us understand the relationships between cell structures and functions that IBM Watson can further analyze. In a sense, we are using cells to give Watson ‘microscopic eyes’ so we can better understand cellular behavior in different conditions, from complex environments to human diseases."
To achieve all these goals, the center aims to convene diverse researchers from many intellectual backgrounds: scientists trained in cell biology will work with physicists, engineers, mathematicians and computer scientists; experimentalists will collaborate with computer modelers and theoreticians; and university researchers will work with their counterparts in commercial companies in order to develop cellular machines with real-world applications. The center will take advantage of UCSF’s QB3 incubator space to encourage the formation of start-up companies.
Priority of Education
Another priority of the center is to educate the next generation of cell engineers and to engender public excitement about the goals of synthetic biology through collaborations with the Exploratorium, as well as outreach through local science festivals, maker faires, and hackathons. The center will also collaborate with UCSF’s Science and Health Education Partnership to host summer cell engineering “Boot Camps” for high school students and teachers from San Francisco Unified School District and across the Bay Area. In addition, undergraduate research internships will be offered to students from SF State, City College of San Francisco and UC Santa Cruz.
“This partnership will allow our students, the majority of whom come from underrepresented backgrounds, the opportunity to gain skills and experience that will help them get into top doctoral programs and make their mark as scientists,” said Frank Bayliss, PhD, a professor of biology at SF State who will serve as diversity director for the new center. “They will be working alongside a diverse group of excellent cell biologists at SF State, as well as outstanding scientists at UCSF and our other partner institutions, on high-level, cutting-edge research that will have a positive impact on society.”
Other members of the new center include Jennifer Fung, PhD, Sophie Dumont, PhD, Shawn Douglas, PhD, Hana El-Samad, PhD, Orion Weiner, PhD, and Matt Thomson, PhD, of UCSF; Mark Chan, PhD, and Diana Chu, PhD, of SF State; Sindy Tang, PhD, and Manu Prakash, PhD, of Stanford; Daniel Fletcher, D.Phil., PhD, of UC Berkeley; and Jennifer Frazier of the Exploratorium.
UC San Francisco (UCSF) is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy; a graduate division with nationally renowned programs in basic, biomedical, translational and population sciences; and a preeminent biomedical research enterprise. It also includes UCSF Health, which comprises top-ranked hospitals, UCSF Medical Center and UCSF Benioff Children’s Hospitals in San Francisco and Oakland – and other partner and affiliated hospitals and healthcare providers throughout the Bay Area.