Let there be machines
New $25M NSF grant will help MIT engineers harness and control the power of biology
A new kind of intelligent design movement may be upon us—one that has its origins at the intersections of biological engineering and the life sciences. Researchers from MIT, along with collaborators at the Georgia Institute of Technology and University of Illinois at Urbana-Champaign, want to take the next step in synthetic biology, which has until now largely worked to reprogram single-celled organisms such as designer bacteria, into engineering completely novel multi-cell life forms. Their goal is to harness nature’s unique capacities for self-assembly, self-repair, self-replication, and adaptation and build biological machines that could help address some of the world’s most critical energy, agriculture, health and environmental challenges.
Funded by a new $25 million award from the National Science Foundation, researchers at the Science and Technology Center on Emergent Behaviors of Integrated Cellular Systems (EBICS) are hoping to build a simple multi-cellular machine within five years, says Roger Kamm, Germeshausen Professor of Mechanical and Biological Engineering and the Center’s founding director. “It’s not as far fetched as it sounds if you break it into smaller steps.”
The first step is to understand how a handful of stem cells replicate and organize themselves into systems. But rather than striving to understand every signal involved in these processes, the EBICS team will tease out the signals that matter, says Kamm, who has a project underway focused on coaxing stem cells into forming vascular networks. “We don’t have to model every signaling pathway in an endothelial cell”—the cells that form blood vessels—“to form a vessel. We might be able to control tube formation with just a few.”
With this knowledge in hand, the next steps will involve applying it to groups of disparate cell types. By combining a variety of cell types—such as signal-sensing and processing neurons, muscle-forming myocytes, vessel-forming endothelial cells, and chemical-producing fibroblasts—the team hopes to create components such as sensors, processors (user-programmed, artificial brains), actuators, and factories. Such an approach will, provide researchers with the modular components that can be used as basic building blocks for more sophisticated living machines. While these “machines” may resemble their mechanical counterparts, the challenges of creating and controlling them differ vastly. “Cells often don’t seem to behave in a nice, deterministic way,” says Kamm. “There is always a random or stochastic element. Yet, despite this variability, cells are able to create with amazing consistency, exquisitely structured networks, organs and organisms.”
This uncertainty raises questions about how to characterize these living machines—which could range from surrogate organs for testing drug toxicity, to self-healing robots, to self-renewing machines that gather and remove toxic waste. To help engineers characterize their creations, and indeed to help them discover which stimuli lead to desired results, EBICS is developing novel imaging and modeling technologies. For instance, MIT scientists have devised biochemical imaging tools that cause molecules to fluoresce when their states change, allowing researchers to measure important biochemical signals as they are released by cells. Illinois scientists have learned that tension is necessary along a nerve fiber to propagate electrical signals. “To accomplish our goals, mechanical, biochemical, and electrical cues all have to be simultaneously regulated and monitored in the local microenvironment of a cell,” says Kamm.
The non-deterministic nature of biology (and life’s ability to attend to its own replication, repair, and assembly), raise questions about whether laying the groundwork for making new life forms is really such a good idea. While the potential benefits to society are enormous, so are the ethical issues. To keep ethical questions at the forefront of discussions, EBICS has partnered with a recently-funded NSF center at Georgia Tech that specializes in ethically contentious research and innovation.
“With the advent of stem cell biology, we can control cell differentiation, and with genomics, we can control cell protein expression and function,” says Jessica Winters, assistant professor of chemical and biomolecular engineering at Ohio State University and a reviewer of the EBICS grant proposal. “Biological machines are a lot like the invention of the transistor,” she adds. “We’re not really sure where they will lead, but we can be sure that the implications will be significant.”
“The interface of engineering and biology provides one of the most fertile areas for research breakthroughs and innovations,” says Sohi Rastegar, Director of the Office of Emerging Frontiers in Research and Innovation at the National Science Foundation. “The systems approach for understanding cell-cell interaction of various types of cells and cell-clusters provides for unique opportunities for the design of purely biological machines with opportunities for breakthroughs—novel technologies with enormous potential to impact a wide variety of applications including manufacturing, clean energy, environment remediation, and advanced healthcare diagnostics and therapies.”—Elizabeth Dougherty