Building Synthetic Memory

Cellular memory - conversion of a transient signal into a sustained response - is a common feature of biological systems. Synthetic biologists aim to understand and re-engineer such systems in a reliable and predictable manner. Synthetic memory circuits have been designed and built in vitro and in vivo based on diverse mechanisms, such as oligonucleotide hybridization, recombination, transcription, phosphorylation, and RNA editing. Thus far, building these circuits has helped us explore the basic principles required for stable memory and ask novel biological questions. Here we discuss strategies for building synthetic memory circuits, their use as research tools, and future applications of these devices in medicine and industry.

[1]  Martin Fussenegger,et al.  From gene switches to mammalian designer cells: present and future prospects. , 2013, Trends in biotechnology.

[2]  J. Gunawardena Multisite protein phosphorylation makes a good threshold but can be a poor switch. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[3]  S. Peltz,et al.  The cap-to-tail guide to mRNA turnover , 2001, Nature Reviews Molecular Cell Biology.

[4]  C-M Ghim,et al.  Two-component genetic switch as a synthetic module with tunable stability. , 2009, Physical review letters.

[5]  B. Séraphin,et al.  Positive feedback in eukaryotic gene networks: cell differentiation by graded to binary response conversion , 2001, The EMBO journal.

[6]  D. Gallie The cap and poly(A) tail function synergistically to regulate mRNA translational efficiency. , 1991, Genes & development.

[7]  J. Collins,et al.  Synthetic Biology Moving into the Clinic , 2011, Science.

[8]  D. Endy,et al.  Rewritable digital data storage in live cells via engineered control of recombination directionality , 2012, Proceedings of the National Academy of Sciences.

[9]  Shankar Srinivas,et al.  Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus , 2001, BMC Developmental Biology.

[10]  Pamela A Silver,et al.  Synthetic memory circuits for tracking human cell fate. , 2012, Genes & development.

[11]  Haisu Ma,et al.  Synthesizing a novel genetic sequential logic circuit: a push-on push-off switch , 2010, Molecular systems biology.

[12]  Javier Macía,et al.  Monomeric Bistability and the Role of Autoloops in Gene Regulation , 2009, PloS one.

[13]  David A. Drubin,et al.  Rational design of memory in eukaryotic cells. , 2007, Genes & development.

[14]  Thomas H Segall-Shapiro,et al.  Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome , 2010, Science.

[15]  P. Silver,et al.  A new approach to an old problem: synthetic biology tools for human disease and metabolism. , 2011, Cold Spring Harbor symposia on quantitative biology.

[16]  M. Fussenegger,et al.  Synthetic biology advancing clinical applications. , 2012, Current opinion in chemical biology.

[17]  Drew Endy,et al.  Amplifying Genetic Logic Gates , 2013, Science.

[18]  Harel Z. Shouval,et al.  Regulation of cytoplasmic polyadenylation can generate a bistable switch , 2012, BMC Systems Biology.

[19]  Jehoshua Bruck,et al.  Neural network computation with DNA strand displacement cascades , 2011, Nature.

[20]  Martin Fussenegger,et al.  Hysteresis in a synthetic mammalian gene network. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[21]  Alfonso Jaramillo,et al.  Computational design of digital and memory biological devices , 2007, Systems and Synthetic Biology.

[22]  Timothy S. Ham,et al.  Design and Construction of a Double Inversion Recombination Switch for Heritable Sequential Genetic Memory , 2008, PloS one.

[23]  J. Ferrell Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability. , 2002, Current opinion in cell biology.

[24]  S. Fraser,et al.  Tracing the lineage of tracing cell lineages , 2001, Nature Cell Biology.

[25]  George M Church,et al.  Towards synthesis of a minimal cell , 2006, Molecular systems biology.

[26]  M. Radman,et al.  A system for detection of genetic and epigenetic alterations in Escherichia coli induced by DNA-damaging agents. , 1985, Journal of molecular biology.

[27]  J. Erickson,et al.  Sex determination in Drosophila: The view from the top , 2010, Fly.

[28]  Teruo Fujii,et al.  Bottom-up construction of in vitro switchable memories , 2012, Proceedings of the National Academy of Sciences.

[29]  Andras Nagy,et al.  Cre recombinase: The universal reagent for genome tailoring , 2000, Genesis.

[30]  Pamela A. Silver,et al.  Making Cellular Memories , 2010, Cell.

[31]  Markus Wieland,et al.  Engineering molecular circuits using synthetic biology in mammalian cells. , 2012, Annual review of chemical and biomolecular engineering.

[32]  James J. Collins,et al.  A Tunable Genetic Switch Based on RNAi and Repressor Proteins for Regulating Gene Expression in Mammalian Cells , 2007, Cell.

[33]  Martin Fussenegger,et al.  Pharmaceutically controlled designer circuit for the treatment of the metabolic syndrome , 2012, Proceedings of the National Academy of Sciences.

[34]  Michael C Jewett,et al.  Synthetic in vitro circuits. , 2012, Current opinion in chemical biology.

[35]  Martin Fussenegger,et al.  Emerging biomedical applications of synthetic biology , 2011, Nature Reviews Genetics.

[36]  Timothy K Lu,et al.  Synthetic circuits integrating logic and memory in living cells , 2013, Nature Biotechnology.

[37]  I. Schreiber,et al.  On the origin of bistability in the Stage 2 of the Huang-Ferrell model of the MAPK signaling. , 2013, The Journal of chemical physics.

[38]  S. Basu,et al.  A synthetic multicellular system for programmed pattern formation , 2005, Nature.

[39]  Liming Wang,et al.  Protein Scaffolds Can Enhance the Bistability of Multisite Phosphorylation Systems , 2012, PLoS Comput. Biol..

[40]  Farren J. Isaacs,et al.  Prediction and measurement of an autoregulatory genetic module , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[41]  M. Fussenegger,et al.  An engineered epigenetic transgene switch in mammalian cells , 2004, Nature Biotechnology.

[42]  M. Ptashne A Genetic Switch , 1986 .

[43]  E. Winfree,et al.  Construction of an in vitro bistable circuit from synthetic transcriptional switches , 2006, Molecular systems biology.

[44]  Farren J. Isaacs,et al.  Programming cells by multiplex genome engineering and accelerated evolution , 2009, Nature.

[45]  J. Collins,et al.  Construction of a genetic toggle switch in Escherichia coli , 2000, Nature.

[46]  Barry Kelly,et al.  Memories , 1997, The Ulster medical journal.

[47]  Pamela A Silver,et al.  Synthetic circuit identifies subpopulations with sustained memory of DNA damage. , 2011, Genes & development.

[48]  Drew Endy,et al.  Design and Analysis of Genetically Encoded Counters , 2012, CSBio.

[49]  Santiago F. Elena,et al.  Robust dynamical pattern formation from a multifunctional minimal genetic circuit , 2009, BMC Systems Biology.

[50]  G. Church,et al.  Synthetic Gene Networks That Count , 2009, Science.