Abstract
Mammalian cells behave as computers: they operate as information-processing systems that dynamically integrate and respond to diverse environmental signals. This is possible thank to a myriad of regulatory circuits consisting of sensitive elements that recognize and bind analytes, and of transducer modules that filter the signals and initiate a cellular response modulating theirs or the behavior of heterologous pathways.
Similarly, synthetic biology has prompted the design of sensors that are connected to precise actuation to either shed light on the behavior of regulatory networks or to implement novel cellular functionalities with diagnostic or therapeutic purposes.
Synthetic biosensors are based on the coupling of sensing and actuation modules that are finely balanced to obtain the desired modularity and specificity. Classically, sensors are defined based on the source of the signals detected: biosensors for environmental signals, biosensors for extracellular chemicals, and biosensors for intracellular chemicals and metabolites. Mammalian synthetic biosensors require further classification that relies on the type of activity involved in the signal-to-gene-activation cascade: transcriptional, posttranscriptional, and translational sensors. This chapter provides an overview of mammalian synthetic biology-based sensors and their architecture and connection to downstream signal processing.
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References
Abel S, Theologis A (1996) Early genes and auxin action. Plant physiology 111(1): 9–17. https://doi.org/10.1104/pp.111.1.9
An CI, Trinh VB, Yokobayashi Y (2006) Artificial control of gene expression in mammalian cells by modulating RNA interference through aptamer-small molecule interaction. RNA 12:710–716. https://doi.org/10.1261/rna.2299306
Ausländer S, Fussenegger M (2013) From gene switches to mammalian designer cells: present and future prospects. Trends Biotechnol 31:155–168. https://doi.org/10.1016/j.tibtech.2012.11.006
Baaske J, Gonschorek P, Engesser R et al (2018) Dual-controlled optogenetic system for the rapid down-regulation of protein levels in mammalian cells. Sci Rep 8:1–10. https://doi.org/10.1038/s41598-018-32929-7
Banaszynski LA, Chen L-C, Maynard-Smith LA et al (2006) A rapid, reversible, and tunable method to regulate protein function in living cells using synthetic small molecules. Cell 126:995. https://doi.org/10.1016/j.cell.2006.07.025
Barnea G, Strapps W, Herrada G et al (2008) The genetic design of signaling cascades to record receptor activation. Proc Natl Acad Sci USA 105:64–69. https://doi.org/10.1073/pnas.0710487105
Black JB, Perez-Pinera P, Gersbach CA (2017) Mammalian synthetic biology: engineering biological systems. Annu Rev Biomed Eng 19:249–277. https://doi.org/10.1146/annurev-bioeng-071516-044649
Boch J, Bonas U (2010) Xanthomonas AvrBs3 family-type III effectors: discovery and function. Annu Rev Phytopathol 48:419–436. https://doi.org/10.1146/annurev-phyto-080508-081936
Bonger KM, Chen L, Liu CW, Wandless TJ (2011) Small-molecule displacement of a cryptic degron causes conditional protein degradation. Nat Chem Biol 7:531–537. https://doi.org/10.1038/nchembio.598
Braselmann S, Graninger P, Busslinger M (1993) A selective transcriptional induction system for mammalian cells based on Gal4-estrogen receptor fusion proteins. Proc Natl Acad Sci USA 90:1657–1661. https://doi.org/10.1073/pnas.90.5.1657
Caliendo F, Dukhinova M, Siciliano V (2019) Engineered Cell-Based Therapeutics: Synthetic Biology Meets Immunology. Frontiers in Bioengineering and Biotechnology 7:43. https://doi.org/10.3389/fbioe.2019.00043
Casini A, Christodoulou G, Freemont PS et al (2014) R2oDNA designer: computational design of biologically neutral synthetic DNA sequences. ACS Synth Biol 3:525–528. https://doi.org/10.1021/sb4001323
Cella F, Siciliano V (2019) Protein-based parts and devices that respond to intracellular and extracellular signals in mammalian cells. Curr Opin Chem Biol 52:47–53. https://doi.org/10.1016/j.cbpa.2019.04.014
Cella F, Wroblewska L, Weiss R, Siciliano V (2018) Engineering protein-protein devices for multilayered regulation of mRNA translation using orthogonal proteases in mammalian cells. Nat Commun 9:4392. https://doi.org/10.1038/s41467-018-06825-7
Chavez A, Scheiman J, Vora S et al (2015) Highly efficient Cas9-mediated transcriptional programming. Nat Methods 12:326–328. https://doi.org/10.1038/nmeth.3312
Chen YY, Jensen MC, Smolke CD (2010) Genetic control of mammalian T-cell proliferation with synthetic RNA regulatory systems. Proc Natl Acad Sci USA 107:8531–8536. https://doi.org/10.1073/pnas.1001721107
Chen Z, Boyken SE, Jia M et al (2018) Programmable design of orthogonal protein heterodimers. Nature 1:106. https://doi.org/10.1038/s41586-018-0802-y
Collins JJ, Khalil AS (2010) Synthetic biology applications come of age. Nat Rev Genet 11:367–379. https://doi.org/10.1038/nrg2775.Synthetic
Di Bernardo D, Marucci L, Menolascina F, Siciliano V (2012) Predicting synthetic gene networks. Methods Mol Biol 813:57–81. https://doi.org/10.1007/978-1-61779-412-4_4
Elbashir SM, Lendeckel W, Tuschl T (2001) RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev 15:188–200. https://doi.org/10.1101/gad.862301
Hammer K, Mijakovic I, Jensen PR (2006) Synthetic promoter libraries – tuning of gene expression. Trends Biotechnol 24:53–55. https://doi.org/10.1016/j.tibtech.2005.12.003
Hirosawa M, Fujita Y, Parr CJC et al (2017) Cell-type-specific genome editing with a microRNA-responsive CRISPR-Cas9 switch. Nucleic Acids Res 45:e118. https://doi.org/10.1093/nar/gkx309
Hirosawa M, Fujita Y, Saito H (2019) Cell-type-specific CRISPR activation with MicroRNA-Responsive AcrllA4 switch. ACS Synth Biol. https://doi.org/10.1021/acssynbio.9b00073
Iwamoto M, Björklund T, Lundberg C et al (2010) A general chemical method to regulate protein stability in the mammalian central nervous system. Chem Biol. https://doi.org/10.1016/j.chembiol.2010.07.009
Jinek M, Chylinski K, Fonfara I et al (2012) A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337:816–821. https://doi.org/10.1126/science.1225829
Katzenellenbogen BS, Katzenellenbogen JA, Medicine C (2000) Estrogen receptor transcription and transactivation Estrogen receptor alpha and estrogen receptor beta: regulation by selective estrogen receptor modulators and importance in breast cancer. Breast Cancer Res 2:33
Kemmer C, Gitzinger M, Daoud-El Baba M et al (2010) Self-sufficient control of urate homeostasis in mice by a synthetic circuit. Nat Biotechnol 28:355–360. https://doi.org/10.1038/nbt.1617
Kim M-S, Kini AG (2017) Engineering and application of zinc finger proteins and TALEs for biomedical research. Mol Cells 40:533–541. https://doi.org/10.14348/molcells.2017.0139
Kim D-S, Gusti V, Pillai SG, Gaur RK (2005) An artificial riboswitch for controlling pre-mRNA splicing. RNA 11:1667–1677. https://doi.org/10.1261/rna.2162205
Kumar D, Il AC, Yokobayashi Y (2009) Conditional RNA interference mediated by allosteric ribozyme. J Am Chem Soc 131:13906–13907. https://doi.org/10.1021/ja905596t
Los GV, Encell LP, Mcdougall MG et al (2008) HaloTag: a novel protein labeling technology for cell imaging and protein analysis. ACS Chem Biol 3:373–382
MacDonald JT, Siciliano V (2017) Computational sequence design with R2oDNA designer. In: Humana Press (ed) Methods in molecular biology. Humana Press, New York, pp 249–262
Maeder ML, Linder SJ, Cascio VM et al (2013) CRISPR RNA-guided activation of endogenous human genes. Nat Methods 10:977–979. https://doi.org/10.1038/nmeth.2598
Mandal M, Breaker RR (2004) Gene regulation by riboswitches. Nat Rev Mol Cell Biol 5:451–463. https://doi.org/10.1038/nrm1403
Meister G, Tuschl T (2004) Mechanisms of gene silencing by double-stranded RNA. Nature 431:343–349. https://doi.org/10.1038/nature02873
Miki K, Endo K, Saito H et al (2015a) Efficient detection and purification of cell populations using synthetic MicroRNA switches cell stem cell resource efficient detection and purification of cell populations using synthetic MicroRNA switches. Stem Cell 16:699–711. https://doi.org/10.1016/j.stem.2015.04.005
Mittal V (2004) Improving the efficiency of RNA interference in mammals. Nat Rev Genet 5:355–365. https://doi.org/10.1038/nrg1323
Miyazaki Y, Imoto H, Chen L-c, Wandless TJ (2012) Destabilizing domains derived from the human estrogen receptor. J Am Chem Soc 23:1–7. https://doi.org/10.1038/jid.2014.371
Moscou MJ, Bogdanove AJ (2009) A simple cipher governs DNA recognition by TAL effectors. Science 326:1501. https://doi.org/10.1126/science.1178817
Neklesa TK, Tae HS, Schneekloth AR et al (2011) Small-molecule hydrophobic tagging-induced degradation of HaloTag fusion proteins. Nat Chem Biol 7:538–543. https://doi.org/10.1038/nchembio.597
Niopek D, Benzinger D, Roensch J et al (2014) Engineering light-inducible nuclear localization signals for precise spatiotemporal control of protein dynamics in living cells. Nat Commun 5:1–11. https://doi.org/10.1038/ncomms5404
Nishimura K, Fukagawa T, Takisawa H et al (2009) An auxin-based degron system for the rapid depletion of proteins in nonplant cells. Nat Methods 6:917–922. https://doi.org/10.1038/nmeth.1401
Nudler E, Mironov AS (2004) The riboswitch control of bacterial metabolism. Trends Biochem Sci 29:11–17. https://doi.org/10.1016/j.tibs.2003.11.004
Parr CJC, Katayama S, Miki K et al (2016) MicroRNA-302 switch to identify and eliminate undifferentiated human pluripotent stem cells. Sci Rep 6:32532. https://doi.org/10.1038/srep32532
Qi LS, Larson MH, Gilbert LA et al (2013) Repurposing CRISPR as an RNA-γuided platform for sequence-specific control of gene expression. Cell 152:1173–1183. https://doi.org/10.1016/j.cell.2013.02.022
Repina NA, Rosenbloom A, Mukherjee A et al (2017) At light speed: advances in Optogenetic Systems for Regulating Cell Signaling and Behavior. Annu Rev Chem Biomol Eng 8:13–39. https://doi.org/10.1146/annurev-chembioeng-060816-101254
Roberts ML, Katsoupi P, Tseveleki V, Taoufik E (2017) Bioinformatically informed design of synthetic mammalian promoters. Methods Mol Biol 1651:93–112. https://doi.org/10.1007/978-1-4939-7223-4_8
Rosenbaum DM, Rasmussen SGF, Kobilka BK (2009) The structure and function of G-protein-coupled receptors. Nature 459:356-363. https://doi.org/10.1038/nature08144
Rössger K, Charpin-El Hamri G, Fussenegger M (2013) Reward-based hypertension control by a synthetic brain-dopamine interface. Proc Natl Acad Sci USA 110:18150–18155. https://doi.org/10.1073/pnas.1312414110
Rost BR, Schneider-Warme F, Schmitz D, Hegemann P (2017) Optogenetic tools for subcellular applications in neuroscience. Neuron 96:572–603. https://doi.org/10.1016/j.neuron.2017.09.047
Sauer B, Henderson N (1988) Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage P1. Proc Natl Acad Sci USA 85:5166–5170. https://doi.org/10.1073/pnas.85.14.5166
Saxena P, Bojar D, Fussenegger M (2017) Mammalian synthetic promoters 1651:263–273. https://doi.org/10.1007/978-1-4939-7223-4
Scheller L, Strittmatter T, Fuchs D et al (2018) Generalized extracellular molecule sensor platform for programming cellular behavior. Nat Chem Biol 14:723–729. https://doi.org/10.1038/s41589-018-0046-z
Siciliano V, Garzilli I, Fracassi C et al (2013) MiRNAs confer phenotypic robustness to gene networks by suppressing biological noise. Nat Commun 4:2364
Siciliano V, Diandreth B, Monel B et al (2018) Engineering modular intracellular protein sensor-actuator devices. Nat Commun 9:1–7. 1881. https://doi.org/10.1038/s41467-018-03984-5
Smole A, Lainšček D, Bezeljak U et al (2017) A synthetic mammalian therapeutic gene circuit for sensing and suppressing inflammation. Mol Ther 25:102–119. https://doi.org/10.1016/j.ymthe.2016.10.005
Stanton BC, Siciliano V, Ghodasara A et al (2014) Systematic transfer of prokaryotic sensors and circuits to mammalian cells. ACS Synth Biol 3:880. https://doi.org/10.1021/sb5002856
Suess B, Hanson S, Berens C et al (2003) Conditional gene expression by controlling translation with tetracycline-binding aptamers. Nucleic Acids Res 31:1853–1858. https://doi.org/10.1093/nar/gkg285
Tucker BJ, Breaker RR (2005) Riboswitches as versatile gene control elements. Curr Opin Struct Biol 15:342–348. https://doi.org/10.1016/j.sbi.2005.05.003
Wan X, Marsafari M, Xu P (2019) Engineering metabolite-responsive transcriptional factors to sense small molecules in eukaryotes: current state and perspectives. Microb Cell Factories 18:1–13. https://doi.org/10.1186/s12934-019-1111-3
Weber W, Fussenegger M (2012) Emerging biomedical applications of synthetic biology. Nat Rev Genet 13:21–35. https://doi.org/10.1038/nrg3094
Werstuck G, Green MR (1998) Controlling gene expression in living cells through small molecule-RNA interactions. Science 282:296–298. https://doi.org/10.1126/science.282.5387.296
Wieland M, Hartig JS (2008) Artificial riboswitches: synthetic mRNA-based regulators of gene expression. Chembiochem 9:1873–1878. https://doi.org/10.1002/cbic.200800154
Win MN, Smolke CD (2007) A modular and extensible RNA-based gene-regulatory platform for engineering cellular function. Proc Natl Acad Sci USA 104:14283–14288. https://doi.org/10.1073/pnas.0703961104
Winkler WC, Breaker RR (2005) Regulation of bacterial gene expression by riboswitches. Annu Rev Microbiol 59:487–517. https://doi.org/10.1146/annurev.micro.59.030804.121336
Wroblewska L, Kitada T, Endo K et al (2015a) Mammalian synthetic circuits with RNA binding proteins delivered by RNA. Nat Biotechnol 33:839–841
Wroblewska L, Kitada T, Endo K et al (2015b) Mammalian synthetic circuits with RNA binding proteins for RNA-only delivery. Nat Biotechnol 33:839–841. https://doi.org/10.1038/nbt.3301
Xie Z, Wroblewska L, Prochazka L et al (2011) Multi-input RNAi-based logic circuit for identification of specific cancer cells. Science 333:1307–1311. https://doi.org/10.1126/science.1205527
Yamada M, Suzuki Y, Nagasaki SC et al (2018) Light control of the Tet gene expression system in mammalian cells. Cell Rep 25:487–500.e6. https://doi.org/10.1016/j.celrep.2018.09.026
Ye H, Daoud-El Baba M, Peng R-W, Fussenegger M (2011) A synthetic optogenetic transcription device enhances blood-glucose homeostasis in mice. Science 332:1565–1568. https://doi.org/10.1126/science.1203535
Yen L, Svendsen J, Lee JS et al (2004) Exogenous control of mammalian gene expression through modulation of RNA self-cleavage. Nature 431:471–476. https://doi.org/10.1038/nature02844
Zhang J, Lau MW, Ferré-D’Amaré AR (2010) Ribozymes and riboswitches: modulation of RNA function by small molecules. Biochemistry 49:9123–9131. https://doi.org/10.1021/bi1012645
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Tedeschi, F., Siciliano, V. (2020). Mammalian Synbio Sensors. In: Thouand, G. (eds) Handbook of Cell Biosensors. Springer, Cham. https://doi.org/10.1007/978-3-319-47405-2_190-1
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DOI: https://doi.org/10.1007/978-3-319-47405-2_190-1
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