Yale Combined Program in the Biological and Biomedical Sciences (BBS): Biochemistry, Quantitative Biology, Biophysics and Structural Biology (BQBS): DNA Dynamics and Transcriptional Regulation; RNA Processing and Ribonucleoprotein Machines
in high-throughput biology and biotechnology have led to an array of biological
insights in medicine, agriculture, evolutionary biology and studies of diverse
organisms. Harnessing the potential of species diversity makes biological
systems ideal to solve defining challenges, such as producing new drugs to
alleviate human disease and generating biologically derived fuels, chemicals
and materials to ensure environmental sustainability. In addition to a thorough understanding of biological
systems, achieving these goals requires safe and programmable control of
biological systems. In this
regard, scientists have been primarily using standard recombinant DNA
technologies, which have enabled our ability to perform genetics, but on a
limited scale. Our ability to
measure and modify genetic and biochemical molecules and their interactions in
pathways, cells and the environment remains a defining challenge. Thus, “basic enabling technologies”
that enhance our ability to engineer biology are needed.
The Isaacs Laboratory is focused on developing foundational cellular and biomolecular engineering technologies to understand and engineer biological systems. Our approach is designed to integrate engineering and evolution through the construction of genes, gene networks and whole genomes alongside quantitative models to gain a better understanding of whole biological systems. In turn, we utilize these insights to design and evolve living cells with new, improved and desired function. We seek to uncover new properties of biological systems and generate new phenotypes with the ultimate goal of applying these insights to address global challenges in medicine, energy supply and the environment.
- 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. (2011) Precise manipulation of chromosomes in vivo enables genome-wide codon replacement. Science, 333(6040):348-53. PMID: 21764749.
- Wang HH*, Isaacs FJ*, Carr PA, Sun ZZ, Xu G, Forest CR, Church GM (2009) Programming cells by multiplex genome engineering and accelerated evolution. Nature, 460(7257):894-8.
- Isaacs FJ, Dwyer DJ, Collins JJ (2006) RNA Synthetic Biology. Nature Biotechnology, 24:545-554.
- Isaacs FJ, Dwyer DJ, Ding C, Pervouchine D, Cantor C and Collins JJ (2004) Engineered Riboregulators Enable Post-Transcriptional Control of Gene Expression. Nature Biotechnology, 22: 841-847.
- Isaacs FJ*, Hasty J*, Cantor CR, Collins JJ (2003) Prediction and Measurement of an Autoregulatory Genetic Module. Proceedings of the National Academy of Sciences USA, 100:7714-7719.
Full List of PubMed Publications
- 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. 2017 Dec 11; 2017 Dec 11. PMID: 29226470
- 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; 2017 Nov 16. PMID: 29153834
- 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; 2017 Feb 2. PMID: 27987323
- 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; 2016 Sep 6. PMID: 27601680
- Ma NJ, Isaacs FJ: Genomic Recoding Broadly Obstructs the Propagation of Horizontally Transferred Genetic Elements. Cell Syst. 2016 Aug; 2016 Jul 14. PMID: 27426981
- 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 Jun 17; 2016 May 11. PMID: 27054880
- Muir P, Li S, Lou S, Wang D, Spakowicz DJ, Salichos L, Zhang J, Weinstock GM, Isaacs F, Rozowsky J, Gerstein M: Erratum to: The real cost of sequencing: scaling computation to keep pace with data generation. Genome Biol. 2016 Apr 28; 2016 Apr 28. PMID: 27125642
- Muir P, Li S, Lou S, Wang D, Spakowicz DJ, Salichos L, Zhang J, Weinstock GM, Isaacs F, Rozowsky J, Gerstein M: The real cost of sequencing: scaling computation to keep pace with data generation. Genome Biol. 2016 Mar 23; 2016 Mar 23. PMID: 27009100
- Taylor ND, Garruss AS, Moretti R, Chan S, Arbing MA, Cascio D, Rogers JK, Isaacs FJ, Kosuri S, Baker D, Fields S, Church GM, Raman S: Engineering an allosteric transcription factor to respond to new ligands. Nat Methods. 2016 Feb; 2015 Dec 21. PMID: 26689263
- Amiram M, Haimovich AD, Fan C, Wang YS, Aerni HR, Ntai I, Moonan DW, Ma NJ, Rovner AJ, Hong SH, Kelleher NL, Goodman AL, Jewett MC, Söll D, Rinehart J, Isaacs FJ: Evolution of translation machinery in recoded bacteria enables multi-site incorporation of nonstandard amino acids. Nat Biotechnol. 2015 Dec; 2015 Nov 16. PMID: 26571098
- Soye BJD, Patel JR, Isaacs FJ, Jewett MC: Repurposing the translation apparatus for synthetic biology. Curr Opin Chem Biol. 2015 Oct; 2015 Jul 15. PMID: 26186264
- 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; 2015 Sep 9. PMID: 26350765
- 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; 2015 Sep 9. PMID: 26350500
- Haimovich AD, Muir P, Isaacs FJ: Genomes by design. Nat Rev Genet. 2015 Sep; 2015 Aug 11. PMID: 26260262
- Gallagher RR, Patel JR, Interiano AL, Rovner AJ, Isaacs FJ: Multilayered genetic safeguards limit growth of microorganisms to defined environments. Nucleic Acids Res. 2015 Feb 18; 2015 Jan 7. PMID: 25567985
- 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. 2015 Feb 5; 2015 Jan 21. PMID: 25607356
- Sawyer N, Gassaway BM, Haimovich AD, Isaacs FJ, Rinehart J, Regan L: Designed phosphoprotein recognition in Escherichia coli. ACS Chem Biol. 2014 Nov 21; 2014 Oct 6. PMID: 25272187
- Gallagher RR, Li Z, Lewis AO, Isaacs FJ: Rapid editing and evolution of bacterial genomes using libraries of synthetic DNA. Nat Protoc. 2014 Oct; 2014 Sep 4. PMID: 25188632
- Ma NJ, Moonan DW, Isaacs FJ: Precise manipulation of bacterial chromosomes by conjugative assembly genome engineering. Nat Protoc. 2014 Oct; 2014 Sep 4. PMID: 25188631
- 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 Apr; 2014 Jan 22. PMID: 24452804
- Hakim A, Nguyen JB, Basu K, Zhu DF, Thakral 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; 2013 Mar 12. PMID: 23486477
- Heinemann IU, Rovner AJ, Aerni HR, Rogulina S, Cheng L, Olds W, Fischer JT, Söll 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; 2012 Sep 13. PMID: 22982858
- 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. PMID: 21764749