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Large-scale design of robust genetic circuits with multiple inputs and outputs for mammalian cells

Related Publications

  • A. A. K. Nielsen, B. S. Der, J. Shin, P. Vaidyanathan, V. Paralanov, E. A. Strychalski, D. Ross, D. Densmore, and C. A. Voigt, “Genetic Circuit Design Automation,” Science, vol. 352, iss. 6281, 2016. 

  • A. J. Keung and A. S. Khalil, "A Unifying Model of Epigenetic Regulation (Perspective)," Science, vol. 351, iss. 661-662, 2016.

  • A. J. Keung, J. K. Joung, A. S. Khalil and J. J. Collins, "Chromatin Regulation at the Frontier of Synthetic Biology," Nature Reviews Genetics, vol. 16, iss. 159-171, 2016.

  • N. Roehner, E. M. Young, C. A. Voigt, B. D. Gordon, and D. Densmore, “Double Dutch: A Tool for Designing Combinatorial Libraries of Biological Systems,” ACS Synthetic biology, 2016. 

  • J. R. Rubens, G. Selvaggio, T. K. Lu, “Synthetic Mixed-signal Computation in Living Cells,” Nature Communications, vol. 7, article 11658, June 3, 2016.

  • M. J. Quintin, N. J. Ma, S. Ahmed, S. Bhatia, A. Lewis, F. J. Isaacs, and D. Densmore, “Merlin: Computer-aided Oligonucleotide Design for Large Scale Genome Engineering with Mage,”ACS Synthetic biology, iss. ja, p. null, 2016. 

  • N. Roehner and D. Densmore, "How to Remember and Revisit Genetic Designs Automatically," 2016. 

  • A. J. Keung, C. J. Bashor, S. Kiriakov, J. J. Collins and A. S. Khalil, "Using Targeted Chromatin Regulators to Engineer Combinatorial and Spatial Transcriptional Regulation," Cell, vol. 158, iss. 110-120, 2014.

Funded Publications


  • Kiwimagi, K.A., Letendre, J.H., Weinberg, B.H., Wang, J., Chen, M., Watanabe, L., Myers, C.J., Beal, J., Wong, Wilson W., Weiss, R. Quantitative characterization of recombinase-based digitizer circuits enables predictable amplification of biological signals. Commun Biol 4, 875 (2021). [PAPER LINK] | [SYNBIOHUB LINK]


  • Bryan Bartley, Jacob Beal, Jonathan Karr, and Elizabeth Strychalski, "Organizing Genome Editing for the Gigabase Scale," Nature Communications 2020


  • Ali Lashkaripou, Christopher Rodriguez, Luis Ortiz, and Douglas Densmore, "Performance Tuning of Microfluidic Flow-Focusing Droplet Generators," Lab on a Chip 2019

  • Nathan Hillson, Mark Caddick, Yizhi Cai, Jose A. Carrasco, Matthew Wook Chang, Natalie C. Curach, David J. Bell, Rosalind Le Feuvre, Douglas C. Friedman, Xiongfei Fu, Nicholas D. Gold, Markus J. Herrgård, Maciej B. Holowko, James R. Johnson, Richard A. Johnson, Jay D. Keasling, Richard I. Kitney, Akihiko Kondo, Chenli Liu, Vincent J.J. Martin, Filippo Menolascina, Chiaki Ogino, Nicola J. Patron, Marilene Pavan, Chueh Loo Poh, Isak S. Pretorius, Susan J. Rosser, Nigel S. Scrutton, Marko Storch, Hille Tekotte, Evelyn Travnik, Claudia E. Vickers, Wen Shan Yew, Yingjin Yuan, Huimin Zhao, Paul S. Freemont, "Building a Global Alliance of Biofoundries," Nature Communications 2019

  • Weinberg, B. H., Cho, J.H., Agarwal, Y., Pham, H. N. T., Caraballo, L. D., Walkosz, M., Ortega, C., Trexler, M., Tague, N., Law, B., Benman, W.K.J., Letendre, J., Beal, J*., and Wong, W.W, "High-Performance Chemical and Light-Inducible Recombinases in Mammalian Cells and Mice," Nature Communications 2019  

  • Chakravarti, D., Caraballo, L.D., Weinberg, B., Wong W. W., "Inducible Gene Switches with Memory in Human T cells for Cellular Immunotherapy," ACS Synthetic Biology 2019

  • Bashor C.J.*, Patel N.*, Choubey S., Beyzavi A., Kondev J., Collins J.J., and Khalil A.S., "Complex Signal Processing in Synthetic Gene Circuits Using Cooperative Regulatory Assemblies," Science 2019

  • Park M., Patel N., Keung A.J. and Khalil A.S., "Engineering Epigenetic Regulation Using Synthetic Read-Write Modules," Cell 2019

  • Heins Z.J, Mancuso C.P., Kiriakov S., Wong B.G., Bashor C.J., and Khalil A.S., "Designing Automated, High-Throughput Continuous Cell Growth Experiments Using eVOLVER," JoVE 2019

  • Jacob Beal, Tramy Nguyen, Thomas E. Gorochowski, Angel Goni-Moreno, James Scott-Brown, James Alastair McLaughlin, Curtis Madsen, Benjamin Aleritsch, Bryan Bartley, Shyam Bhakta, Mike Bissell, Sebastian Castillo Hair, Kevin Clancy, Augustin Luna, Nicolas Le Novere, Zach Palchick, Matthew Pocock, Herbert Sauro, John T. Sexton, Jeffrey J. Tabor, Christopher A. Voigt, Zach Zundel, Chris Myers, and Anil Wipat, "Communicating Structure and Function in Synthetic Biology Diagrams," ACS Synthetic Biology 2019

  • Nicholas Roehner, Bryan Bartley, Jacob Beal, James McLaughlin, Matthew Pocock, Michael Zhang, Zach Zundel, and Chris J. Myers, "Specifying Combinatorial Designs with the Synthetic Biology Open Language (SBOL)," ACS Synthetic Biology 2019

  • Curtis Madsen, Angel Goni Moreno, Umesh P, Zachary Palchick, Nicholas Roehner, Christian Atallah, Bryan Bartley, Kiri Choi, Robert Sidney Cox, Thomas Gorochowski, Raik Grunberg, Chris Macklin, James McLaughlin, Xianwei Meng, Tramy Nguyen, Matthew Pocock, Meher Samineni, James Scott-Brown, Ysis Tarter, Michael Zhang, Zhen Zhang, Zach Zundel, Jacob Beal, Michael Bissell, Kevin Clancy, John H. Gennari, Goksel Misirli, Chris Myers, Ernst Oberortner, Herbert Sauro, Anil Wipat, "Synthetic Biology Open Language (SBOL) Version 2.3," Journal of Integrative Bioinformatics 2019

  • Curtis Madsen, Angel Goni Moreno, Zachary Palchick, Umesh P, Nicholas Roehner, Bryan Bartley, Swapnil Bhatia, Shyam Bhakta, Mike Bissell, Kevin Clancy, Robert Sidney Cox, Thomas Gorochowski, Raik Grunberg, Augustin Luna, James McLaughlin, Tramy Nguyen, Nicolas Le Novere, Matthew Pocock, Herbert Sauro, James Scott-Brown, John T. Sexton, Guy-Bart Stan, Jeffrey J. Tabor, Christopher A. Voigt, Zach Zundel, Chris Myers, Jacob Beal, Anil Wipat, "Synthetic Biology Open Language Visual (SBOL Visual) Version 2.1," Journal of Integrative Bioinformatics 2019

  • Jacob Beal, Cassandra Overney, Aaron Adler, Fusun Yaman, Lisa Tiberio, and Meher Samineni, "TASBE Flow Analytics: A Package for Calibrated Flow Cytometry Analysis," ACS Synthetic Biology 2019

  • Bryan A. Bartley, Jacob Beal, Jonathan R. Karr, Elizabeth A. Strychalski, "Organizing Genome Engineering for the Gigabase Scale," Under Review



  • Zheng X., Beyzavi A., Krakowiak J., Patel N., Khalil A.S. and Pincus D. Hsf1, "Phosphorylation Generates Cell-to-Cell Variation in Hsp90 levels and Promotes Phenotypic Plasticity," Cell Reports 2018

  • Wong B.G.*, Mancuso C.P.*, Kiriakov S., Bashor C.J. and Khalil A.S. Precise, "Automated Control of Conditions for High-Throughput Growth of Yeast and Bacteria with eVOLVER," Nature Biotechnology 2018

  • Walsh, D.I.; Pavan, M.; Ortiz, L.; Wick, S.; Bobrow, J.; Guido, N.J.; Leinicke, S.; Fu, D.; Pandit, S.;Qin, L.; Carr, P.A., Douglas Densmore, "Standardizing Automated DNA Assembly: Best Practices, Metrics, and Protocols Using Robots," SLAS Technology 2018

  • Park M., Patel N., Keung A.J. and Khalil A.S., "Engineering Epigenetic Regulation using Synthetic Read-Write Modules," Cell 2018

  • Göksel Misirli, Tramy Nguyen , James Alastair McLaughlin, Prashant Vaidyanathan, Timothy S. Jones, Douglas Densmore ,Chris Myers, and Anil Wipat, "A Computational Workflow for the Automated Generation of Models of Genetic Designs," ACS Synthetic Biology 2018

  • A. Lashkaripour, R. Silva, and D. Densmore, "Desktop Micromilled Microfluidics," Microfluidics and Nanofluidics, vol 22, iss. 31, 2018.

  • P. Chen, Y. Qian, and D. Del Vecchio, "A Model of Resource Competition in CRISPR-mediated Gene Repression," Proc. IEEE Conf. Decision and Control, 2018 (to appear)


  • C. McBride and D. Del Vecchio, "Resource Sensor Design for Quantifying Resource Competition in Genetic Circuits," Proc. IEEE Conf. Decision and Control, 2018 (to appear)


  • McBride and D. Del Vecchio, "The Steady State Landscape of Resource Constrained Nonlinear Positive Dynamical Systems," Under Review (Automatica) 2018


  • Newby G.A.*, Kiriakov S.*, Hallacli E.*, Kayatekin C., Tsvetkov P., Mancuso C.P., Bonner, J.M., Hesse W.R., Chakrabortee S., Manogaran A.L., Liebman S.W., Lindquist S. and Khalil A.S., "A Genetic Tool to Track Protein Aggregates and Control Prion Inheritance," Cell 2017

  • L. Ortiz, M. Pavan, L. McCarthy, J. Timmons, D. M. Densmore, "Automated Robotic Liquid Handling Assembly of Modular DNA Devices," JoVE 2017

  • B. H. Weinberg, H. N. T. Pham, L. D. Caraballo, T. Lozanoski, A. Engel, S. Bhatia, W. W. Wong, "Large-scale Design of Robust Genetic Circuits with Multiple Inputs and Outputs for Mammalian Cells," Nature Biotechnology, 2017.

  • C. McBride and D. Del Vecchio, "Analyzing and Exploiting the Effects of Protease Sharing in Genetic Circuits," Proc. of International Federation of Automatic Control World Congress, 2017.​

  • C. Myers, J. Beal, T. E. Gorochowski, H. Kuwahara, C. Madsen, J. A. McLaughlin, G. Misirli, T. Nguyen, E. Oberortner, M. Samineni, A. Wipat, M. Zhang, and Z. Zundel, "A Standard-enabled Workflow for Synthetic Biology," Biochemical Society Transactions, vol. 45, iss. 3, 2017.

  • D. I. Walsh, D. S. Kong, S. K. Murthy,  P. A. Carr, "Enabling Microfluidics: from Clean Rooms to Makerspaces," Trends in Biotechnology, 2017.

  • D. S. Kong, T. A. Thorsen, J. Babb, S. T. Wick, J. J. Gam, R. Weiss, and P. A. Carr, "Open-source, Community-driven Microfluidics with Metafluidics," Nature Biotechnology, 2017.

  • G. A. Newby, S. Kiriakov, E. Hallacli, C. Kayatekin, P. Tsvetkov, C. P. Mancuso, J. Maeve Bonner, W. R. Hesse, S. Chakrabortee, A. L. Manogaran, S. W. Liebman, S. Lindquist, and A. S. Khalil, "A Genetic Tool to Track Protein Aggregates and Control Prion Inheritance," Cell, vol. 171, iss. 4, 2017. 

  • L. Ortiz, M. Pavan, L. McCarthy, J. Timmons,  D. M. Densmore, "Automated Robotic Liquid Handling Assembly of Modular DNA Devices," Journal of Visualized Experiments, 2017.

  • R. Shah and D. Del Vecchio, "Signaling Architectures that Transmit Unidirectional Signals Despite Retroactivity," Biophysical Journal, 113(3):728-742, 2017


  • C. McBride, "A Mathematical and Engineering Framework to Predict the Effects of Resource Sharing on Genetic Networks," MIT, Mechanical Engineering Department Master’s Thesis. May 2017

  •  Y. Qian, C. McBride and D. Del Vecchio, "Programming Cells to Work for Us," Annual Reviews in Control, Robotics and Automation systems, 1:411-440, 2017 

  • S. Bhatia, M. J. Smanski, C. A. Voigt, and D. Densmore, "Genetic Design via Combinatorial Constraint Specification," ACS Synthetic Biology, vol. 6, iss. 11, 2017.

  • J. Beal, N. DeLateur, B. Teague, R. Weiss, J. Sexton, S. Castillo-Hair, and J. J. Tabor, "Toward Quantitative Comparison of Fluorescent Protein Expression Levels via Fluorescent Beads," International Workshop on Bio-Design Automation, 2017.

  • S. B. Carr, J. Beal, and D. M. Densmore, “Reducing DNA Context Dependence in Bacterial Promoters,” PLOS ONE, vol. 12, iss. 4, 2017.

  • R. S. Cox, J. A. McLaughlin, R. Grunberg, J. Beal, A. Wipat, and H. M. Sauro, "A Visual Language for Protein Design,", ACS Synthetic Biology, 2017.

  • J. Beal, "Biochemical Complexity Drives Log-Normal Variation in Genetic Expression," IET Engineering Biology, iss. 1, 2017.



  • Park M., Keung A.J. and Khalil A.S., "The Epigenome: the Next Substrate for Engineering." Genome Biology 2016

  • C. McBride and D. Del Vecchio, "Analyzing and Exploiting the Effects of Protease Sharing in Genetic Circuits," Proc. of IFAC World Congress, July 2016 (Invited paper)

  • J. Beal, A. Adler, and F. Yaman, "Managing Bioengineering Complexity with AI Techniques," Elsevier Biosystems, vol. 148, 2016.

  • J. Beal, "Mathematical Foundations of Variation in Gene Expression," IET/SynbiCITE Engineering Biology Conference, 2016.

  • A. Gyorgy and D. Del Vecchio, "Price and Utility of Protein in Synthetic Gene Circuits," PLOS, 2016.

  • J. Beal, R. S. Cox, R. Grunberg, J. McLaughlin, T. Nguyen, C. Macklin, M. Bissell, C. Madsen, N. Roehner, E. Oberortner, G. Misirli, K. Clancy, M. Pocock, Z. Zhang, C. Myers, M. Zhang, M. Samineni, Z. Zundel, B. Bartley, K. Choi, J. H. Gennari, and H. Sauro, "Synthetic Biology Open Language (SBOL) Version 2.1.0," Journal of Integrative Bioinformatics, 2016.

  • J. Beal, T. Haddock-Angelli, M. Gershater, K. de Mora, M. Lizarazo, J. Hollenhorst, R. Rettberg, and iGEM Interlab Study Contributors, "Reproducibility of Fluorescent Expression from Engineered Biological Constructs in E. coli," PLoS One, 2016.

  • L. Woodruff, T. E. Gorochowski, N. Roehner, T. S. Mikkelsen, D. Densmore, D. B. Gordon, R. Nicol, and C. A. Voigt, "Registry in a Tube: Multiplexed Pools of Retrievable Parts for Genetic Design Space Exploration," Nucleic Acids Research, vol. 45, iss. 3, 2016.

  • M. Park, A. J. Keung and A. S. Khalil, "The Epigenome: The Next Substrate for Engineering," Genome Biology, vol. 17, iss. 183, 2016.

  • N. J. Hillson, H. A. Plahar, J. Beal, and R. Prithviraj, "Improving Synthetic Biology Communication: Recommended Practices for Visual Depiction and Digital Submission of Genetic Designs," ACS Synthetic Biology, 2016.

  • N. Roehner, J. Beal, K. Clancy, B. Bartley, G. Misirli, R. Grunberg, E. Oberortner, M. Pocock, M. Bissell, C. Madsen, T. Nguyen, M. Zhang, Z. Zhang, Z. Zundel, D. Densmore, J. H. Gennari, A. Wipat, H. M. Sauro, and C. J. Myers, "Sharing Structure and Function in Biological Design with SBOL 2.0," ACS Synthetic Biology, 2016.

  • N. Roquet and A. P. Soleimany and A. C. Ferris and S. Aaronson and T. K. Lu, "Synthetic Recombinase-based State Machines in Living Cells," Science, vol. 353, iss. 6297, 2016.

  • R. Shah and D. Del Vecchio, "An n-stage Cascade of Phosphorylation Cycles as an Insulation Device for Synthetic Biological Circuits," Proc. of European Conf. on Control, 2016.

  • S. Bhatia, C. LaBoda, V. Yanez, T. Haddock-Angelli, and D. Densmore, "Permutation Machines," ACS Synthetic Biology, vol. 5, iss. 8, 2016.

  • S. Perli*, C. Cui*, T. K. Lu, “Continuous Genetic Recording with Self-Targeting CRISPR-Cas in Human Cells,” Science, 2016.

  • Z. Zhang, T. Nguyen, N. Roehner, G. Misirli, M. Pocock, E. Oberortner, M. Samineni, Z. Zundel, J. Beal, K. Clancy, A. Wipat, and Chris Myers, "libSBOLj 2.0: A Java Library to Support SBOL 2.0," IEEE Life Sciences Letters, 2016.

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