Publications
Adamala KP, Agashe D, Belkaid Y, Bittencourt DMC, Cai Y, Chang MW, Chen IA, Church GM, Cooper VS, Davis MM, Devaraj NK, Endy D, Esvelt KM, Glass JI, Hand TW, Inglesby TV, Isaacs FJ, James WG, Jones JDG, Kay MS, Lenski RE, Liu C, Medzhitov R, Nicotra ML, Oehm SB, Pannu J, Relman DA, Schwille P, Smith JA, Suga H, Szostak JW, Talbot NJ, Tiedje JM, Venter JC, Winter G, Zhang W, Zhu X, Zuber MT. Confronting risks of mirror life . Science . 2024 Dec 12:eads9158. doi: 10.1126/science.ads9158. Epub ahead of print. PMID: 39666824.
Hemez C, Mohler K, Radford F, Moen J, Rinehart J, Isaacs FJ. Genomically recoded Escherichia coli with optimized functional phenotypes. bioRxiv 2024.08.29.610322; doi: https://doi.org/10.1101/2024.08.29.610322
Ciaccia PN*, Liang Z*, Schweitzer AY, Metzner E, Isaacs FJ. Enhanced eMAGE applied to identify genetic factors of nuclear hormone receptor dysfunction via combinatorial gene editing . Nature Communications 15:5218 (2024). https://doi.org/10.1038/s41467-024-49365-z
Asin-Garcia E, Garcia-Morales L, Bartholet T, Liang Z, Isaacs FJ, Martins dos Santos VAP. Metagenomics harvested genus-specific single-stranded DNA-annealing proteins improve and expand recombineering in Pseudomonas species . Nucleic Acids Research 2023, gkad1024, https://doi.org/10.1093/nar/gkad1024 .
Radford F, Rinehart J, Isaacs FJ. Mapping the in vivo fitness landscape of a tethered ribosome . Science Advances . Sci Adv. 2023 Apr 28;9(17):eade8934. doi: 10.1126/sciadv.ade8934. Epub 2023 Apr 28. PMID: 37115918.
Zomorrodi AR, Hemez C, Arranz-Gibert P, Wu T, Isaacs FJ, Segrè D. Computational design and engineering of an Escherichia coli strain producing the nonstandard amino acid para -aminophenylalanine . iScience . 2022 Jun 9;25(7):104562. doi: 10.1016/j.isci.2022.104562. PMID: 35789833; PMCID: PMC9249619.
Patel JR*, Oh J*, Wang S, Crawford JM, Isaacs FJ. Cross-kingdom expression of synthetic genetic elements promotes discovery of metabolites in the human microbiome . Cell 2022,185, 1-19. doi: 10.1016/j.cell.2022.03.008
Mackelprang R, Adamala KP, Aurand ER, Diggans J, Ellington AD, Evans SW, Fortman JL “Clem”, Hillson NJ, Hinman AW, Isaacs FJ, Medford JI, Mamaghani S, Moon TS, Palmer MJ, Peccoud J, Vitalis EA, Hook-Barnard I, Friedman DC. Making Security Viral: Shifting engineering biology culture and publishing . ACS Synth. Biol. 2022, 11, 2, 522-7. doi: 10.1021/acssynbio.1c00324
Shapiro DM, Mandava G, Yalcin SE, Arranz-Gibert P, Dahl P, Shipps C, Gu Y, Srikanth V, Salazar Morales AI, O’Brien JP, Vanderschuren K, Vu D, Batista V, Malvankar NS, Isaacs FJ. Protein nanowires with tunable functionality and programmable self-assembly using sequence-controlled synthesis . Nat Commun . 2022 Feb 11; 13, 829. doi: 10.1038/s41467-022-28206-x.
Vanderschuren K*, Arranz-Gibert P*, Khang M*, Hadar D*, Gaudin A, Yang F, Folta-Stogniew E, Saltzman WM, Amiram M, Isaacs FJ. Tuning protein half-life in mouse using sequence-defined biopolymers functionalized with lipids . Proceedings of the National Academy of Sciences . 2022 119(4) e2103099119. doi: 10.1073/pnas.2103099119.
Radford F, Elliott SD, Schepartz A, Isaacs FJ. Targeted editing and evolution of engineered ribosomes by filtered editing . Nat Commun . 2022 Jan 10;13(1):180. doi: 10.1038/s41467-021-27836-x. PMID: 35013328.
Arranz-Gibert P*, Vanderschuren K*, Haimovich A, Halder A, Gupta K, Rinehart J, Isaacs FJ. Chemoselective restoration of para-azido-phenylalanine at multiple sites in proteins . Cell Chem Biol . 2021 Dec 16:S2451-9456(21)00516-X. doi: 10.1016/j.chembiol.2021.12.002. Epub ahead of print. PMID: 34965380.
Schiapparelli P, Pirman NL, Mohler K, Miranda-Herrera PA, Zarco N, Kilic O, Miller C, Shah SR, Rogulina S, Hungerford W, Abriola L, Hoyer D, Turk BE, Guerrero-Cazares H, Isaacs FJ, Quiñones-Hinojosa A, Levchenko A, Rinehart J. Phosphorylated WNK kinase networks in recoded bacteria recapitulate physiological function . Cell Reports . 2021 Jul 20;36(3):109416. doi: 10.1016/j.celrep.2021.109416. PMID: 34289367.
Zhang CH, Spasov KA, Reilly RA, Hollander K, Stone EA, Ippolito JA, Liosi ME, Deshmukh MG, Tirado-Rives J, Zhang S, Liang Z, Miller SJ, Isaacs F, Lindenbach BD, Anderson KS, Jorgensen WL. Optimization of triarylpyridinone inhibitors of the main protease of SARS-CoV-2 to low-nanomolar antiviral potency . ACS Med. Chem. Lett . 2021 Jul 14; 12(8):1325-1332. doi: 10.1021/acsmedchemlett.1c00326. eCollection 2021 Aug 12.
Mackelprang R, Aurand ER, Bovenberg RAL, Brink KR, Charo RA, Delborne JA, Diggans J, Ellington AD, Fortman JLC, Isaacs FJ, Medford JI, Murray RM, Noireaux V, Palmer MJ, Zoloth L, Friedman DC. Guiding Ethical Principles in Engineering Biology Research . ACS Synthetic Biology . 2021 May 21;10(5):907-910. doi: 10.1021/acssynbio.1c00129. Epub 2021 May 12. PMID: 33977723.
Grome MW & Isaacs FJ. ZTCG: Viruses expand the genetic alphabet . Science . 2021 Apr 30: 372(6541):460-461. doi: 10.1126/science.abh3571.
Tang T-C, Tham E, Liu X, Yehl K, Rovner AJ, Yuk H, de la Fuente-Nunez C, Isaacs FJ, Zhao X, Lu TK. Hydrogel-based biocontainment of bacteria for continuous sensing and computation . Nat Chem Biol . 2021 Apr 5. doi:10.1038/s41589-021-00779-6. Epub ahead of print. PMID: 33820990
Zhang CH, Stone EA, Deshmukh M, Ippolito JA, Ghahremanpour MM, Tirado-Rives J, Spasov KA, Zhang S, Takeo Y, Kudalkar SN, Liang Z, Isaacs F, Lindenbach B, Miller SJ, Anderson KS, Jorgensen WL. Potent Noncovalent Inhibitors of the Main Protease of SARS-CoV-2 from Molecular Sculpting of the Drug Perampanel Guided by Free Energy Perturbation Calculations . ACS Cent Sci . 2021 Mar 24;7(3):467-475. doi: 10.1021/acscentsci.1c00039. Epub 2021 Feb 22. PMID: 33786375; PMCID: PMC7931627.
Wannier TM, Ciaccia PN, Ellington AD, Filsinger GT, Isaacs FJ, Javanmardi K, Jones MA, Kunjapur AM, Nyerges A, Pal C, Schubert MG, Church GM. Recombineering and MAGE . Nature Reviews Methods Primers . 2021, 1:7. https://doi.org/10.1038/s43586-020-00006-x .
Williams ND, Landajuela A, Kasula RK, Zhou W, Powell JT, Xi Z, Isaacs FJ, Berro J, Toomre D, Karatekin, Lin C. DNA-Origami-Based Fluorescence Brightness Standards for Convenient and Fast Protein Counting in Live Cells . Nano Lett . 2020 Nov 9. doi: 10.1021/acs.nanolett.0c03925.
Liang Z, Metzner E, Isaacs FJ. Advanced eMAGE for highly efficient combinatorial editing of a stable genome . bioRxiv 2020.08.30.256743; doi: https://doi.org/10.1101/2020.08.30.256743 .
Arranz-Gibert P, Patel JR, Isaacs FJ. The role of orthogonality in genetic code expansion . Life. 2019, 9(3), 58 doi: 10.3390/life9030058.
Costa SA, Mozhdehi D, Dzuricky MJ, Isaacs FJ, Brustad EM, Chilkoti A. Active Targeting of Cancer Cells by Nanobody Decorated Polypeptide Micelle with Bio-orthogonally Conjugated Drug . Nano Lett . 2019 Jan 9;19(1):247-254. doi:10.1021/acs.nanolett.8b03837.
Ma N*, Hemez C*, Barber KW*, Rinehart J, Isaacs FJ. Organisms with alternative genetic codes resolve unassigned codons via mistranslation and ribosomal rescue . eLife . 2018 Oct 30;7. pii: e34878. doi: 10.7554/eLife.34878.
Arranz-Gibert P, Vanderschuren K, Isaacs FJ. Next-generation genetic code expansion . Curr Opin in Chem Biol . 2018 Jul 30. pii: S1367-5931(18)30065-6. doi: 10.1016/j.cbpa.2018.07.020.
Barber K, Muir P, Szeligowski RV, Rogulina S, Gerstein M, Sampson JR, Isaacs FJ, Rinehart J. Encoding human serine phosphopeptides in bacteria for proteome-wide identification of phosphorylation-dependent interactions . Nat Biotechnol . 2018 Aug;36(7):638-644.
Martin RW, Des Soye BJ, Kwon YC, Kay J, Davis RG, Thomas PM, Majewska NI, Chen CX, Marcum RD, Weiss MG, Stoddart AE, Amiram M, Ranji Charna AK, Patel JR, Isaacs FJ, Kelleher NL, Hong SH, Jewett MC. Cell-free protein synthesis from genomically recoded bacteria enables multisite incorporation of noncanonical amino acids . Nat Commun . 2018 Mar 23;9(1):1203.
Costa SA, Simon JR, Amiram M, Tang L, Zauscher S, Brustad EM, Isaacs FJ, Chilkoti A. Photo-Crosslinkable Unnatural Amino Acids Enable Facile Synthesis of Thermoresponsive Nano- to Microgels of Intrinsically Disordered Polypeptides . Adv Mater . 2018 Feb;30(5). doi: 10.1002/adma.201704878.
Barbieri EM, Muir P, Akhuetie-Oni BO, Yellman CM, Isaacs FJ. Precise Editing at DNA Replication Forks Enables Multiplex Genome Engineering in Eukaryotes . Cell . 2017 Nov 30;171(6):1453-1467.e13. doi: 10.1016/j.cell.2017.10.034.
Gan R, Perez JG, Carlson ED, Ntai I, Isaacs FJ, Kelleher NL, Jewett MC. Translation system engineering in Escherichia coli enhances non-canonical amino acid incorporation into proteins . Biotechnol Bioeng . 2017 May;114(5):1074-1086. doi: 10.1002/bit.26239.
Napolitano MG, Landon M, Gregg CJ, Lajoie MJ, Govindarajan L, Mosberg JA, Kuznetsov G, Goodman DB, Vargas-Rodriguez O, Isaacs FJ, Söll D, Church GM. Emergent rules for codon choice elucidated by editing rare arginine codons in Escherichia coli . Proc Natl Acad Sci U S A . 2016 Sep 20;113(38):E5588-97. doi: 10.1073/pnas.1605856113.
Ma NJ, Isaacs FJ. Genomic Recoding Broadly Obstructs the Propagation of Horizontally Transferred Genetic Elements . Cell Systems . 2016 Jul 16. Doi: 10.1016/j.cels.2016.06.009.
Boeke JD, Church G, Hessel A, Kelley NJ, Arkin A, Cai Y, Carlson R, Chakravarti A, Cornish VW, Holt L, Isaacs FJ, Kuiken T, Lajoie M, Lessor T, Lunshof J, Maurano MT, Mitchell LA, Rine J, Rosser S, Sanjana NE, Silver PA, Valle D, Wang H, Way JC, Yang L. The Genome Project—Write . Science . 2016 Jun 2. 10.1126.science.aaf6850.
Quintin M, Ma NJ, Ahmed S, Bhatia S, Lewis A, Isaacs FJ, Densmore D. Merlin: Computer-Aided Oligonucleotide Design for Large Scale Genome Engineering with MAGE . ACS Synth Biol . 2016 May 11. PMID: 27054880
Muir P, Li S, Lou S, Wang D, Spakowicz DJ, Salichos L, Zhang J, Weinstock GM, Isaacs FJ, Rozowsky J, Gerstein M. The real cost of sequencing: scaling computation to keep pace with data generation . Genome Biology . 2016 Mar 23; 17:53 DOI 10.1186/s13059-016-0917-0.
Taylor ND, Garruss AS, Moretti R, Chan S, Arbing MA, Cascio D, Roger JK, Isaacs FJ, Kosuri S, Baker D, Fields S, Church GM, Raman S. Engineering an allosteric transcription factor to respond to new ligands . Nature Methods. 2016 Feb;13(2):177-83. doi: 10.1038/nmeth.3696. Epub 2015 Dec 21.
Amiram M, Haimovich AD, Fan C, Wang Y-S, Aerni H-R, Ntai I, Moonan DW, Ma NJ, Rovner AJ, Hong SH, Kelleher NL, Goodman AL, Jewett MC, Söll D, Rinehart J, Isaacs FJ. Evolution of orthogonal translation components in recoded bacteria enables multi-site incorporation of nonstandard amino acids . Nature Biotechnology , Epub 2015 Nov 16. doi:10.1038/nbt.3372.
Pirman NL, Barber KW, Aerni HR, Ma NJ, Haimovich AD, Rogulina S, Isaacs FJ, Rinehart J. A flexible codon in genomically recoded Escherichia coli permits programmable protein phosphorylation. Nat Commun. 2015 Sep 9;6:8130. doi: 10.1038/ncomms9130.
Oza JP, Aerni HR, Pirman NL, Barber KW, Ter Haar CM, Rogulina S, Amrofell MB, Isaacs FJ, Rinehart J, Jewett MC. Robust production of recombinant phosphoproteins using cell-free protein synthesis. Nat Commun. 2015 Sep 9;6:8168. doi: 10.1038/ncomms9168.
Haimovich AD, Muir P, Isaacs FJ. Genomes by design. Nature Reviews Genetics . 2015 Aug 11. doi: 10.1038/nrg3956.
Des Soye BJ*, Patel JR*, Isaacs FJ, Jewett MC. Repurposing the translation apparatus for synthetic biology . Current Opinion in Chemical Biology . 28:83-90 (2015).
Rovner AJ, Haimovich AD, Katz SR, Li Z, Grome MW, Gassaway BM, Amiram M, Patel JR, Gallagher RR, Rinehart J, Isaacs FJ. Recoded organisms engineered to depend on synthetic amino acids . Nature . doi: 10.1038/nature14095 (2015).
Gallagher RR, Patel JR, Interiano AL, Rovner AJ, Isaacs FJ. Multilayered genetic safeguards limit growth of microorganisms to defined environments . Nucleic Acids Research . doi: 10.1093/nar/gku1378 (2015).
Sawyer J, Gassaway B, Haimovich AD, Isaacs FJ, Rinehart J, Regan L. Designed phosphoprotein recognition in Escherichia coli . ACS Chemical Biology. 9:2502-7 (2014).
Gallagher R, Li Z, Lewis A, Isaacs FJ. Rapid editing and evolution of bacterial genomes using libraries of synthetic DNA . Nature Protocols. 9:2301-2316 (2014).
Ma N, Moonan D, Isaacs FJ. Precise manipulation of bacterial chromosomes by conjugative assembly genome engineering . Nature Protocols. 9:2285-2300 (2014).
Gregg CJ, Lajoie MJ, Napolitano MG, Mosberg JA, Goodman DB, Aach J, Isaacs FJ, Church GM. Rational optimization of tolC as a powerful dual selectable marker for genome engineering . Nucleic Acids Res. 2014 Jan 22.
Bazak L, Haviv A, Barak M, Jacob-Hirsch J, Deng P, Zhang R, Isaacs FJ, Rechavi G, Li JB, Eisenberg E, Levanon EY. A-to-I RNA editing occurs at over a hundred million genomic sites, located in a majority of human genes . Genome Res. 2013 Dec 17.
Hong SH, Ntai I, Haimovich A, Kelleher N, Isaacs FJ, Jewett, M. Cell-free protein synthesis from a release factor 1 deficient Escherichia coli activates efficient and multiple site-specific non-standard amino acid incorporation . ACS Synthetic Biology. 2014.
Lajoie MJ, Rovner AJ, Goodman DB, Aerni HR, Haimovich AD, Kuznetsov G, Mercer JA, Wang HH, Carr PA, Mosberg JA, Rohland N, Schultz PG, Jacobson JM, Rinehart J, Church GM, Isaacs FJ. Genomically recoded organisms expand biological functions . Science. 2013 Oct 18;342(6156):357-60. doi: 10.1126/science.1241459. PubMed PMID: 24136966
Hakim A, Nguyen, JB, Basu K, Zhu DF, Thakrai D, Davies PL, Isaacs FJ, Modis Y, Meng W. Crystal structure of an insect antifreeze protein and its implications for ice binding . J Biol Chem. 2013 Apr 26;288(17): 12295-304. PMID: 23486477.
*Heinemann IU, *Rovner AJ, Aerni HR, Rogulina S, Cheng L, Olds W, Fischer JT, Soll D, Isaacs FJ, Rinehart J. Enhanced phosphoserine insertion during Escherichia coli protein synthesis via partial UAG codon reassignment and release factor 1 deletion . FEBS Lett. 2012 Oct 19;587(20):3716-22. Epub 2012 Sep 13. PMID: 22982858.
Carr PA, Wang HH, Sterling B, Isaacs FJ, Lajoie MJ, Xu G, Church GM, Jacobson JM. Enhanced multiplex genome engineering through co-operative oligonucleotide co-selection . Nucleic Acids Res. 2012 May 25. [Epub ahead of print] PubMed PMID: 22638574.
Isaacs FJ. Automated Design of RNA Devices . Nat Chem Biol . 2012 Apr 17;8(5):413-5. doi: 10.1038/nchembio.942. PubMed PMID: 22510661.
Isaacs FJ*, Carr PA*, Wang HH*, Lajoie MJ, Sterling B, Kraal L, Tolonen AC, Gianoulis TA, Goodman DB, Reppas NB, Emig CJ, Bang D, Hwang SJ, Jewett MC, Jacobson JM, Church GM. Precise manipulation of chromosomes in vivo enables genome-wide codon replacement . Science . 2011 Jul 15;333(6040):348-53. PMID: 21764749.
Callura JM, Dwyer DJ, Isaacs FJ, Cantor CR, Collins JJ. Tracking, tuning, and terminating microbial physiology using synthetic riboregulators . Proc Natl Acad Sci U S A . 2010 Sep 7;107(36):15898-903. Epub 2010 Aug 16. PMID: 20713708.
Wang HH*, Isaacs FJ*, Carr PA, Sun ZZ, Xu G, Forest CR, Church GM. Programming cells by multiplex genome engineering and accelerated evolution . Nature . 2009 Aug 13;460(7257):894-8. Epub 2009 Jul 26. PMID: 19633652.
Isaacs FJ, You L. A brave new synthetic world . A report of the first meeting on ‘Frontiers in Synthetic Biology’, Boston, USA, 1-2 December 2008. Genome Biol . 2009 Feb 3;10(2):302. PMID: 19226443.
Blake WJ, Balázsi G, Kohanski MA, Isaacs FJ, Murphy KF, Kuang Y, Cantor CR, Walt DR, Collins JJ. Phenotypic consequences of promoter-mediated transcriptional noise . Mol Cell . 2006 Dec 28;24(6):853-65. PMID: 17189188.
Isaacs FJ, Dwyer DJ, Collins JJ. RNA synthetic biology . Nat Biotechnol . 2006 May;24(5):545-54. PMID: 16680139.
Isaacs FJ, Blake WJ, Collins JJ. Signal processing in single cells . Science . 2005 Mar 25;307(5717):1886-8. PMID: 15790834.
Isaacs FJ, Collins JJ. Plug-and-play with RNA . Nat Biotechnol . 2005 Mar;23(3):306-7. PMID: 15765083.
Isaacs FJ, Dwyer DJ, Ding C, Pervouchine DD, Cantor CR, Collins JJ. Engineered riboregulators enable post-transcriptional control of gene expression . Nat Biotechnol . 2004 Jul;22(7):841-7. Epub 2004 Jun 20. PMID: 15208640.
Blake WJ, Isaacs FJ. Synthetic biology evolves . Trends Biotechnol . 2004 Jul;22(7):321-4. PMID: 15245901.
Isaacs FJ*, Hasty J*, Cantor CR, Collins JJ. Prediction and measurement of an autoregulatory genetic module . Proc Natl Acad Sci U S A . 2003 Jun 24;100(13):7714-9. Epub 2003 Jun 13. PMID: 12808135.
Hasty J, Isaacs F, Dolnik M, McMillen D, Collins JJ. Designer gene networks: Towards fundamental cellular control . Chaos . 2001 Mar;11(1):207-220. PMID: 12779454.
Hasty J, McMillen D, Isaacs F, Collins JJ. Computational studies of gene regulatory networks: in numero molecular biology . Nat Rev Genet . 2001 Apr;2(4):268-79. PMID: 11283699.