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ILP Institute Insider

April 7, 2014

Mastering the Biological and Engineering Worlds

Rahul Sarpeshkar bridges biology and engineering to advance research and applications in biotechnology, medicine, and supercomputing.

Steve Calechman

Rahul Sarpeshkar describes himself as an “amphibian” researcher. It’s a necessary quality in order to do research in the wet and dry worlds that he inhabits and bridges. As head of the Analog Circuits and Biological Systems Group, he designs biological systems in two domains: the wet world of DNA-protein molecular circuits in living cells and the dry world of electronic circuits on supercomputing chips.

Professor Rahul Sarpeshkar
Research Lab of Electronics
Since energy usage is one of Sarpeshkar’s prime focuses, his lab also looks to create ultra low-power medical implants and the renewable energy cells that power them. The ultimate effect of his work and research means improved molecular sensing and synthesis, which could transform implants to aid with hearing, sight, and paralysis, could improve the treatment of systemic diseases, such as cancer and diabetes, and could reengineer living cells to sense, actuate, compute, communicate, and provide energy.

Moving in Two Worlds
The ability to do both wet and dry work at an advanced level is not typical. Sarpeshkar can do it because he made a fundamental discovery that the same thermodynamic physical laws that cause electron flow in transistors also govern molecular flow in chemical reactions. The effect of such a finding is far-reaching. “I can literally take some advanced electronic analog circuits and then map them into DNA-protein circuits, and vice versa,” he says. “It gives us a very unifying way to synthesize and analyze circuits in both the wet and the dry domains.”

The deep connections between electronics and chemistry that Sarpeshkar identified offer possibilities for fundamentally rethinking design methodologies for biotechnology, medicine, and energy. The ability to engineer cells means improved molecular sensing, processing, and synthesis for the pharmaceutical, energy, and food industries. In medicine, there’s the potential for engineering cells to better treat cancer and diabetes, e.g., for designing immune cells that could not only detect a cancer cell but also kill it.

On the supercomputing chip side, Sarpeshkar says that his research works in the opposite direction, by helping to discover problems with cancer and diabetes genes, drug design and cancer treatments through highly parallel computational modeling. His supercomputing chips will also provide a tool to design biological circuits in cells efficiently.

Underlying all of his work is the idea of energy efficiency. One of his main projects has been designing ultra low-power, implantable medical devices, particularly for the deaf, blind, and paralyzed. Sarpeshkar has been working on creating a fuel cell that harvests energy from glucose, metabolizes it, and creates a battery to power these and other medical implants.

As Sarpeshkar says, glucose makes sense as a power source. It’s energy-dense – consider the sustaining effect of one teaspoon of peanut butter. His fuel cell would actually mimic how biology works since biological cells also harvest energy from glucose and use it to make a proton battery that powers their needs. The upsides are that the implant would be antenna-free and battery-free, last the lifetime of the patient and be self-powered without needing any more complicated intervention than eating. “As soon as people power themselves, they power the implant,” he says, adding that the technology could apply to brain implants and pacemakers. “These glucose-powered medical devices could revolutionize the field of medical implants,” Sarpeshkar says.

The Power of Analog Circuits and Analog Computation
There are essential reasons that Sarpeshkar concentrates on analog circuits and biological systems. Analog computation is significantly more efficient than digital computation and it’s the way that biological cells naturally operate. Digital computation uses 1’s and 0’s, on’s and off’s, and Boolean logic to compute. The purely digital strategy is not sufficient for the operation of biological cells to be efficient.

Cells have an incredibly limited amount of energy per unit time that they can metabolize to power themselves, and also a highly limited set of parts, associated with only about 20,000 genes. Cells must be reengineered efficiently or the metabolic burden and high molecular toxicity of the synthetic circuits can become too high and cause them to fail. Therefore, both synthetic and natural circuits need to get more out of less. Since cells cannot afford to use only black-and-white digital signals and logic to function and compute, Sarpeshkar has shown that they must also utilize the power of grayscale analog signals and the power of analog physics and chemistry to compute.

Over the years, his group’s research has shown that analog computation is practical. One of his group members recently engineered a bacterium to compute a square root and other analog functions using only two genetic parts. Others who tried to do the same computation digitally had to use 130 molecular parts. “Analog synthetic biology has the promise of scaling,” he says, adding that it naturally solves problems that have prevented purely digital synthetic biology from scaling.

In another example of the wet and dry worlds coming together, Sarpeshkar has worked on building revolutionary electronic circuits that are inspired by biology. A few years ago, he and researchers in his lab created a radio-frequency chip that could analyze wireless signals over a wide spectrum extremely quickly. This chip mimicked how the ear analyzed the spectrum of sound signals. Currently, he says that he’s investigating circuits inspired by cell biology, which are able to do massively parallel collective analog computing that is insensitive to noise and that can perform reliable computation with unreliable parts.

Speaking Different Languages
For Sarpeshkar, there’s a practicality in seemingly disparate parts collaborating. It applies when working outside of the university setting as well. While there may be different bottom lines, he says that engaging with the private sector grounds his research by bringing in a real-world focus. As an example, he says that small details that might not always be considered important by academia end up being essential when working with industry. Quoting Ludwig Boltzmann, whose laws of physics are the ones that Sarpeshkar exploited to unify biological and electronic circuit design, he says, “That which is the most fundamental is also the most practical.”

And in his lab itself, there’s the interdisciplinary effect from mastering the wet domain of biology and the dry one of engineering. “It’s a synergistic positive feedback loop,” he says. But he does not think that interdisciplinarity automatically manifests by just assembling a team of experts. It is difficult to bring together a biologist and engineer and expect them to speak the same language or to communicate deeply. As Sarpeshkar says, fish don’t naturally interact with land animals; they inhabit different domains. But by bridging the two worlds in one person or intimately in one unified way of thinking, the possibilities increase. “If you’re an amphibian you really can understand both the commonalities and the differences in both fields deeply and work with high creativity and discipline,” he says.