Synthetic biology of cell signaling

Synthetic biology often takes cues from complex natural networks and pathways to create novel biological systems. The design modalities used in synthetic systems generally follow the different classes of gene regulation in cells such as transcriptional, post-transcriptional and post-translational regulation. The latter class is most prominent in cell signaling pathways that operate via multitude of protein–protein interactions. Engineering signaling pathways is a relatively unexplored area. This review discussed the work toward signaling pathway engineering in diverse biological contexts including bacteria, yeast, vertebrate, and plant cells. While creating synthetic signaling cascades is perhaps one of the most challenging tasks in synthetic biology, potential implications can be far-reaching and include new tools for programming cells and tissues, artificial developmental processes, and therapeutic tools.

[1]  B. Bassler,et al.  Quorum sensing in bacteria. , 2001, Annual review of microbiology.

[2]  W. Lim,et al.  Rewiring cellular morphology pathways with synthetic guanine nucleotide exchange factors , 2007, Nature.

[3]  Daniel J. Lee,et al.  Optogenetic stimulation of the cochlear nucleus using channelrhodopsin-2 evokes activity in the central auditory pathways , 2014, Brain Research.

[4]  Christopher A. Voigt,et al.  Synthetic biology: Engineering Escherichia coli to see light , 2005, Nature.

[5]  Katherine C. Chen,et al.  Sniffers, buzzers, toggles and blinkers: dynamics of regulatory and signaling pathways in the cell. , 2003, Current opinion in cell biology.

[6]  J. Hoch,et al.  Two-component and phosphorelay signal transduction. , 2000, Current opinion in microbiology.

[7]  O. Fackler,et al.  Cell motility through plasma membrane blebbing , 2008, The Journal of cell biology.

[8]  M. Gossen,et al.  Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[9]  E. Mills,et al.  Ca2+-mediated synthetic biosystems offer protein design versatility, signal specificity, and pathway rewiring. , 2011, Chemistry & biology.

[10]  T. Hwa,et al.  Identification of direct residue contacts in protein–protein interaction by message passing , 2009, Proceedings of the National Academy of Sciences.

[11]  E. Isacoff,et al.  Light-activated ion channels for remote control of neuronal firing , 2004, Nature Neuroscience.

[12]  D. Koshland,et al.  An amplified sensitivity arising from covalent modification in biological systems. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[13]  M. Kawahara,et al.  Engineering cytokine receptors to control cellular functions , 2010 .

[14]  U. Deuschle,et al.  Tetracycline-reversible silencing of eukaryotic promoters , 1995, Molecular and cellular biology.

[15]  Timothy K Lee,et al.  Single-cell NF-κB dynamics reveal digital activation and analogue information processing , 2010, Nature.

[16]  L. Johnson.  The regulation of protein phosphorylation. , 2009, Biochemical Society transactions.

[17]  Jessica A. Cardin,et al.  Noninvasive optical inhibition with a red-shifted microbial rhodopsin , 2014, Nature Neuroscience.

[18]  K. Deisseroth,et al.  Ultrafast optogenetic control , 2010, Nature Neuroscience.

[19]  Martin Fussenegger,et al.  A synthetic multifunctional mammalian pH sensor and CO2 transgene-control device. , 2014, Molecular cell.

[20]  M. Elowitz,et al.  A synthetic oscillatory network of transcriptional regulators , 2000, Nature.

[21]  S. Hohmann,et al.  A fungicide-responsive kinase as a tool for synthetic cell fate regulation , 2015, Nucleic acids research.

[22]  Christopher A. Voigt,et al.  A Synthetic Genetic Edge Detection Program , 2009, Cell.

[23]  Tanja Kortemme,et al.  Control of protein signaling using a computationally designed GTPase/GEF orthogonal pair , 2012, Proceedings of the National Academy of Sciences.

[24]  M. Fussenegger,et al.  A Synthetic Optogenetic Transcription Device Enhances Blood-Glucose Homeostasis in Mice , 2011, Science.

[25]  R. Weiss,et al.  A universal RNAi-based logic evaluator that operates in mammalian cells , 2007, Nature Biotechnology.

[26]  Thierry Mora,et al.  Constraint satisfaction problems and neural networks: A statistical physics perspective , 2008, Journal of Physiology-Paris.

[27]  M. Inouye,et al.  A monomeric histidine kinase derived from EnvZ, an Escherichia coli osmosensor , 2000, Molecular microbiology.

[28]  C. Bashor,et al.  References and Notes Supporting Online Material Using Engineered Scaffold Interactions to Reshape Map Kinase Pathway Signaling Dynamics , 2022 .

[29]  Yaakov Benenson,et al.  Transplantation of prokaryotic two-component signaling pathways into mammalian cells , 2014, Proceedings of the National Academy of Sciences.

[30]  Terence Hwa,et al.  Inference of direct residue contacts in two-component signaling. , 2010, Methods in enzymology.

[31]  W. Gilbert,et al.  The lac operator is DNA. , 1967, Proceedings of the National Academy of Sciences of the United States of America.

[32]  David Y. Thomas,et al.  Phosphorylation of the MAPKKK Regulator Ste50p in Saccharomyces cerevisiae: a Casein Kinase I Phosphorylation Site Is Required for Proper Mating Function , 2003, Eukaryotic Cell.

[33]  P. Sorger,et al.  Sequential Application of Anticancer Drugs Enhances Cell Death by Rewiring Apoptotic Signaling Networks , 2012, Cell.

[34]  K. Takeda,et al.  CD28-independent costimulation of T cells by OX40 ligand and CD70 on activated B cells. , 1999, Journal of immunology.

[35]  M. Labow,et al.  A chimeric mammalian transactivator based on the lac repressor that is regulated by temperature and isopropyl beta-D-thiogalactopyranoside. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Mauricio S. Antunes,et al.  A synthetic de-greening gene circuit provides a reporting system that is remotely detectable and has a re-set capacity. , 2006, Plant biotechnology journal.

[37]  D. Iber,et al.  The plasticity of TGF-beta signaling , 2011, 1111.0201.

[38]  Soon Ho Hong,et al.  Engineered fumarate sensing Escherichia coli based on novel chimeric two-component system. , 2013, Journal of biotechnology.

[39]  H. Berg,et al.  A modular gradient-sensing network for chemotaxis in Escherichia coli revealed by responses to time-varying stimuli , 2010, Molecular systems biology.

[40]  Wendell A. Lim,et al.  Rewiring MAP Kinase Pathways Using Alternative Scaffold Assembly Mechanisms , 2003, Science.

[41]  J. Collins,et al.  Programmable cells: interfacing natural and engineered gene networks. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[42]  Xin Wang,et al.  Optogenetic Stimulation of Locus Ceruleus Neurons Augments Inhibitory Transmission to Parasympathetic Cardiac Vagal Neurons via Activation of Brainstem α1 and β1 Receptors , 2014, The Journal of Neuroscience.

[43]  M. Fussenegger,et al.  Streptogramin-based gene regulation systems for mammalian cells , 2000, Nature Biotechnology.

[44]  G. Gambetta,et al.  Genetic engineering of phytochrome biosynthesis in bacteria , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[45]  M. Croft,et al.  Ox-40 ligand: a potent costimulatory molecule for sustaining primary CD4 T cell responses. , 1998, Journal of immunology.

[46]  E. Elion,et al.  Differential input by Ste5 scaffold and Msg5 phosphatase route a MAPK cascade to multiple outcomes , 2004, The EMBO journal.

[47]  M. Brattain,et al.  The maximal size of protein to diffuse through the nuclear pore is larger than 60 kDa , 2007, FEBS letters.

[48]  M. Ptashne,et al.  Specific Binding of the λ Phage Repressor to λ DNA , 1967, Nature.

[49]  B. Roska,et al.  Optogenetic therapy for retinitis pigmentosa , 2011, Gene Therapy.

[50]  J. Tyson,et al.  Design principles of biochemical oscillators , 2008, Nature Reviews Molecular Cell Biology.

[51]  B. Lunt,et al.  Dissecting the Specificity of Protein-Protein Interaction in Bacterial Two-Component Signaling: Orphans and Crosstalks , 2011, PloS one.

[52]  L. Serrano,et al.  Engineering Signal Transduction Pathways , 2010, Cell.

[53]  J. Sheen,et al.  Two-component circuitry in Arabidopsis cytokinin signal transduction , 2001, Nature.

[54]  Yaakov Benenson,et al.  Synthetic biology with RNA: progress report. , 2012, Current opinion in chemical biology.

[55]  María-Eugenia Guazzaroni,et al.  Bacterial sensor kinases: diversity in the recognition of environmental signals. , 2010, Annual review of microbiology.

[56]  S. Chervitz,et al.  The two-component signaling pathway of bacterial chemotaxis: a molecular view of signal transduction by receptors, kinases, and adaptation enzymes. , 1997, Annual review of cell and developmental biology.

[57]  Amy B Tyszkiewicz,et al.  Activation of protein splicing with light in yeast , 2008, Nature Methods.

[58]  L. Delbaere,et al.  Histidine phosphorylation in biological systems. , 2008, Biochimica et biophysica acta.

[59]  Homme W Hellinga,et al.  Engineering key components in a synthetic eukaryotic signal transduction pathway , 2009, Molecular systems biology.

[60]  J. Monod,et al.  Genetic regulatory mechanisms in the synthesis of proteins. , 1961, Journal of molecular biology.

[61]  T. Pawson,et al.  Oncogenic re-wiring of cellular signaling pathways , 2007, Oncogene.

[62]  M Ikura,et al.  Molecular and structural basis of target recognition by calmodulin. , 1995, Annual review of biophysics and biomolecular structure.

[63]  H. Heslop,et al.  A chimeric T cell antigen receptor that augments cytokine release and supports clonal expansion of primary human T cells. , 2005, Molecular therapy : the journal of the American Society of Gene Therapy.

[64]  E. Bamberg,et al.  Channelrhodopsin-2, a directly light-gated cation-selective membrane channel , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[65]  M. Fussenegger,et al.  Macrolide-based transgene control in mammalian cells and mice , 2002, Nature Biotechnology.

[66]  Matias D. Zurbriggen,et al.  Orthogonal optogenetic triple-gene control in Mammalian cells. , 2014, ACS synthetic biology.

[67]  Oreste Acuto,et al.  CD28-mediated co-stimulation: a quantitative support for TCR signalling , 2003, Nature Reviews Immunology.

[68]  Y. Benenson.  Biomolecular computing systems: principles, progress and potential , 2012, Nature Reviews Genetics.

[69]  David L Porter,et al.  Chimeric antigen receptor therapy for cancer. , 2014, Annual review of medicine.

[70]  Javier Macía,et al.  Distributed biological computation with multicellular engineered networks , 2011, Nature.

[71]  Pablo A. Iglesias,et al.  Optimal Noise Filtering in the Chemotactic Response of Escherichia coli , 2006, PLoS Comput. Biol..

[72]  Mauricio S. Antunes,et al.  Programmable Ligand Detection System in Plants through a Synthetic Signal Transduction Pathway , 2011, PloS one.

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

[74]  C. Vinson,et al.  A heterodimerizing leucine zipper coiled coil system for examining the specificity of a position interactions: amino acids I, V, L, N, A, and K. , 2002, Biochemistry.

[75]  K. Curran,et al.  Chimeric antigen receptors for T cell immunotherapy: current understanding and future directions , 2012, The journal of gene medicine.

[76]  M. Ptashne.  Specific binding of the lambda phage repressor to lambda DNA. , 1967, Nature.

[77]  Feng Li,et al.  Cell culture processes for monoclonal antibody production , 2010, mAbs.

[78]  M. Laub,et al.  Specificity in two-component signal transduction pathways. , 2007, Annual review of genetics.

[79]  J. Rowley.  The Philadelphia chromosome translocation a paradigm for understanding leukemia , 1990 .

[80]  M. Wilkinson,et al.  Control of the eukaryotic cell cycle by MAP kinase signaling pathways , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[81]  T. Geiger,et al.  Development and application of receptor-modified T lymphocytes for adoptive immunotherapy. , 2001, Transfusion medicine reviews.

[82]  Huong Le,et al.  Dynamic gene expression for metabolic engineering of mammalian cells in culture. , 2013, Metabolic engineering.

[83]  R. Utsumi,et al.  Functional Characterization in Vitro of All Two-component Signal Transduction Systems from Escherichia coli* , 2005, Journal of Biological Chemistry.

[84]  M. Thattai,et al.  Attenuation of noise in ultrasensitive signaling cascades. , 2002, Biophysical journal.

[85]  James J. Collins,et al.  Tunable Signal Processing in Synthetic MAP Kinase Cascades , 2011, Cell.

[86]  Reinhart Heinrich,et al.  Mathematical models of protein kinase signal transduction. , 2002, Molecular cell.

[87]  Michael T. Laub,et al.  Rewiring the Specificity of Two-Component Signal Transduction Systems , 2008, Cell.

[88]  R. M. Hughes,et al.  Light-mediated control of DNA transcription in yeast. , 2012, Methods.

[89]  Indrani Bose,et al.  Singularity in Polarization: Rewiring Yeast Cells to Make Two Buds , 2009, Cell.

[90]  J. Ferrelljr,et al.  Tripping the switch fantastic: how a protein kinase cascade can convert graded inputs into switch-like outputs , 1996 .

[91]  Michel Sadelain,et al.  Targeting tumours with genetically enhanced T lymphocytes , 2003, Nature Reviews Cancer.

[92]  Chao Tang,et al.  A light-inducible organelle-targeting system for dynamically activating and inactivating signaling in budding yeast , 2013, Molecular biology of the cell.

[93]  Andreas Möglich,et al.  Engineering of a red-light–activated human cAMP/cGMP-specific phosphodiesterase , 2014, Proceedings of the National Academy of Sciences.

[94]  Feng Zhang,et al.  Channelrhodopsin-2 and optical control of excitable cells , 2006, Nature Methods.

[95]  Dagmar Iber,et al.  plasticity of TGF-β signaling , 2011, BMC Systems Biology.