Synthetic Analog and Digital Computation in Living Cells

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Thursday, October 31, 2013 - 4:30pm

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Synthetic biology is an emerging engineering discipline for introducing novel functionalities into living systems. Synthetic biology promises to revolutionize our ability to leverage biology for a wide range of applications and our understanding of natural systems in disease and in health. Despite major progress over the last decade, significant challenges still hamper the design-build-test cycle for synthetic biology. These hurdles include poor predictive models, a lack of scalable parts libraries, inefficient circuit architectures, and low-throughput characterization techniques.

To tackle these issues, we have focused our research on establishing scalable foundational platforms engineering biological systems. Extensible platforms for biological computation in living cells would enable new applications in biotechnology and new strategies for studying basic biology. We described scalable frameworks for eukaryotic transcriptional regulation and novel strategies for implementing digital and analog computation with synthetic gene circuits. We have developed synthetic transcriptional regulation platforms that enable scalable tuning of transcriptional activity, specificity, and cooperativity1. Our digital computational paradigm enables integrated cellular decision-making and logic in living cells for the first time and can be achieved with libraries of orthogonal recombinases2. Our strategy for implementing analog computation enables wide-dynamic-range biosensing and complex mathematical functions with a parsimonious set of devices3. We envision that future efforts in synthetic biology will integrate both digital and analog computation into hybrid state-machines to achieve application-specific goals.

1.    Khalil, A., Lu, T.K., Bashor, C., Ramirez, C., Pyenson, N., Joung, J.K. & Collins, J.J. A Synthetic Biology Framework for Programming Eukaryotic Transcription Functions. Cell 150, 647-658 (2012)

2.    Siuti, P., Yazbek, J. & Lu, T.K. Synthetic circuits integrating logic and memory in living cells. Nat Biotechnol (2013)

3.    Daniel, R., Rubens, J.R., Sarpeshkar, R. & Lu, T.K. Synthetic analog computation in living cells. Nature 497, 619-623 (2013)


Timothy Lu, M.D., Ph.D. is an Assistant Professor leading the Synthetic Biology Group in the Department of Electrical Engineering and Computer Science and the Department of Biological Engineering at MIT. He is also an Associate Member at the Broad Institute, a Member of the MIT Computational and Systems Biology Initiative and the MIT Microbial Science and Engineering Program, and a cofounder of Sample6 Technologies. Tim received his S.B. and M.Eng. in Electrical Engineering and Computer Science from MIT. He also received his Ph.D. in Electrical and Biomedical Engineering from the Harvard-MIT Health Sciences Program. He completed his M.D. training at Harvard Medical School. Tim’s research focuses on engineering fundamental technologies to enable scalable biological systems and on applying synthetic biology to solve important medical and industrial problems, such as antimicrobial resistance and biofilms.

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