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Award Detail

Awardee:REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE
Doing Business As Name:University of California-Berkeley
PD/PI:
  • Jay D Keasling
  • (510) 495-2620
  • jdkeasling@lbl.gov
Award Date:07/14/2006
Estimated Total Award Amount: $ 15,966,647
Funds Obligated to Date: $ 37,433,392
  • FY 2008=$3,798,739
  • FY 2012=$5,026,101
  • FY 2011=$4,368,274
  • FY 2013=$4,308,362
  • FY 2015=$1,906,731
  • FY 2010=$4,588,649
  • FY 2007=$3,570,614
  • FY 2006=$3,167,969
  • FY 2009=$3,824,689
  • FY 2014=$2,873,264
Start Date:07/01/2006
End Date:12/31/2016
Transaction Type: Cooperative Agreements
Agency:NSF
Awarding Agency Code:4900
Funding Agency Code:4900
CFDA Number:47.041
Primary Program Source:040100 NSF RESEARCH & RELATED ACTIVIT
Award Title or Description:Synthetic Biology Engineering Research Center (SynBERC)
Federal Award ID Number:0540879
DUNS ID:124726725
Parent DUNS ID:071549000
Program:ENGINEERING RESEARCH CENTERS
Program Officer:
  • Carmina Londono
  • (703) 292-7053
  • clondono@nsf.gov

Awardee Location

Street:Sponsored Projects Office
City:BERKELEY
State:CA
ZIP:94710-1749
County:Berkeley
Country:US
Awardee Cong. District:13

Primary Place of Performance

Organization Name:University of California-Berkeley
Street:Sponsored Projects Office
City:BERKELEY
State:CA
ZIP:94710-1749
County:Berkeley
Country:US
Cong. District:13

Abstract at Time of Award

Project Summary Synthetic biology is the design and construction of new biological entities such as enzymes, genetic circuits, and cells or the redesign of existing biological systems. Synthetic biology builds on advances in molecular, cell, and systems biology and seeks to transform biology in the same way that synthesis transformed chemistry and integrated circuit design transformed computing. Just as engineers now design integrated circuits based on known physical properties of materials and then fabricate functioning circuits and entire processors (with relatively high reliability), synthetic biologists will soon design and fabricate biological entities to accomplish a particular task. To make this happen, biological materials properties (gene sequences, protein properties, natural genetic circuit design) must be formulated into a set of design rules that can then be used to engineer new biological entities. The Synthetic Biology Engineering Research Center (SynBERC) will lay the foundation for synthetic biology. The research program will develop the foundational understanding and technologies to build biological components and assemble them into an integrated system to accomplish a particular task. The Center's specific aims are 1) to develop a conceptual framework for designing small biological components (parts) that can be assembled into devices that will perform a well-characterized function under specified conditions, 2) to develop a small number of chasses (stable, robust bacterial hosts with known responses) to host the engineered devices and to assemble several devices to accomplish a larger vision or goal, 3) to develop a set of standards for the interactions of the parts and devices so that the devices can be built more readily and reproducibly, 4) to offer the parts, devices, and chasses as open source to other researchers and companies and 5) understand the biological and societal risks associated with synthetic biology and integrate these into the design process. These objectives will be achieved through four thrust areas in 1) Parts and Part Composition, 2) Devices and Device Composition, 3) Chassis Design, Construction, and Characterization, and 4) Societal Issues in Synthetic Biology. Two testbed applications will drive development of the thrusts. The resulting parts, devices, and chasses will be managed through a distributed web of Registries of Standard Biological Parts. SynBERC will offer a complementary education program that will 1) educate a new cadre of biological engineers capable of designing biological components, just as electrical engineers design and build integrated circuits, 2) educate the general public about the benefits and possible risks of synthetic biology, 3) educate public policy students and policy-makers about the benefits and real threats of synthetic biology, and 4) educate K-12 students about the opportunities offered by careers in science, engineering, and synthetic biology. Coupled with a strong outreach program to minority institutions and local community colleges and high schools, SynBERC will increase the participation of minority students in this emerging area and encourage high-school students to enter this exciting new area of engineering. The new discipline, synthetic biology, will transform the biotechnology, high-technology, pharmaceutical, and chemical industries as well as suppliers of genetic tools and custom DNA synthesis companies. SynBERC will partner with key companies in these sectors to invite applications for and advice on our research program, to provide internships for undergraduate and graduate students, to speed technology transfer, and to develop SynBERC funding. Intellectual merit. Synthetic Biology will transform the field of biology into an engineering discipline by introducing into biology the concepts developed in other fields of engineering: ready access to off-the-shelf parts and devices with standard connections; a substrate onto which one can assemble the parts and devices and a power supply for the devices; standards for the basic components to enable their ready integration into a larger functional system; and open-source availability of parts, devices, and chasses. These developments will make the engineering of biology easier and more predictable. SynBERC brings together many of the pioneers (biologists and engineers from world-class institutions) of synthetic biology to work together to lay the foundation for this nascent field. Broader impacts. Synthetic biology (catalyzed by SynBERC) will transform the biotechnology, high-technology, pharmaceutical, and chemical industries, as well as suppliers of genetic tools and custom DNA synthesis companies. SynBERC will educate a new cadre of synthetic biologists and biological engineers capable of designing biological parts and useful biological systems. Finally, SynBERC's education program will provide general information on synthetic biology for the general public, in-depth offerings for public policy professionals, and motivational information on opportunities in higher education for K-12 students.

Publications Produced as a Result of this Research

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Martin CH, Wu D, Prather KL "Integrated bioprocessing for the pH-dependent production of 4-valerolactone from levulinate in Pseudomonas putida KT2440." Appl Environ Microbiol 76, v., 2010, p.417-424.

Garcia DE, Baidoo EE, Benke PI, Pingitore F, Tang YJ, Villa S, Keasling JD. "Separation and mass spectrometry in microbial metabolomics." Curr Opin Microbiol., v.11(3), 2008, p.233.

Gaucher SP, Redding AM, Mukhopadhyay A, Keasling JD, Singh AK. "Post-translational modifications of Desulfovibrio vulgaris Hildenborough sulfate reduction pathway proteins." J Proteome Res., v.7(6), 2008, p.2320.

Mukhopadhyay A, Redding AM, Rutherford BJ, Keasling JD. "Importance of systems biology in engineering microbes for biofuel production." Curr Opin Biotechnol., v.19(3), 2008, p.228.

Yoon SH, Lee SH, Das A, Ryu HK, Jang HJ, et al. "Combinatorial expression of bacterial whole mevalonate pathway for the production of beta-carotene in E. coli." J Biotechnol 140, v., 2009, p.218-226.

Hale V, Keasling JD, Renninger N, Diagana TT. "Microbially derived artemisinin: a biotechnology solution to the global problem of access to affordable antimalarial drug." Am J Trop Med Hyg., v.77(6), 2007, p.198.

Lee SK, Keasling JD. "Heterologous protein production in Escherichia coli using the propionate-inducible pPro system by conventional and auto-." Protein Expr Purif., v.61, 2008, p.197.

Anthony JR, Anthony LC, Nowroozi F, Kwon G, Newman JD, Keasling JD. "Optimization of the mevalonate-based isoprenoid biosynthetic pathway in Escherichia coli for production of the anti-mala." Metab Eng., v.11, 2009, p.19.

Moon TS, Yoon SH, Ching MJTM, Lanza AM, Prather KLJ "Enzymatic assay of D-glucuronate using uronate dehydrogenase." Analytical Biochemistry 392, v., 2009, p.183-185.

Humphris EL, Kortemme T "Prediction of protein-protein interface sequence diversity using flexible backbone computational protein design." Structure 16, v., 2008, p.1777-1788.

Price MN, Dehal PS, Arkin AP "FastTree: computing large minimum evolution trees with profiles instead of a distance matrix." Mol Biol Evol 26, v., 2009, p.1641-1650.

Bashor CJ, Helman NC, Yan S, Lim WA. "Using engineered scaffold interactions to reshape MAP kinase pathway signaling dynamics." Science., v.319(586, 2008, p.1539.

Eames M, Kortemme T. "Structural mapping of protein interactions reveals differences in evolutionary pressures correlated to mRNA level and pr." Structure., v.15(11), 2007, p.1442.

Jo WJ, Loguinov A, Chang M, Wintz H, Nislow C, Arkin AP, Giaever G, Vulpe CD. "Identification of genes involved in the toxic response of Saccharomyces cerevisiae against iron and copper overload by p." Toxicol Sci., v.101, 2008, p.140.

Tang YJ, Sapra R, Joyner D, Hazen TC, Myers S, et al. "Analysis of metabolic pathways and fluxes in a newly discovered thermophilic and ethanol-tolerant Geobacillus strain." Biotechnol Bioeng 102, v., 2009, p.1377-1386.

Widmaier DM, Tullman-Ercek D, Mirsky EA, Hill R, Govindarajan S, et al. "Engineering the Salmonella type III secretion system to export spider silk monomers." Molecular Systems Biology 5, v., 2009, p..

Nathan A. Sallee, Brian J. Yeh, and Wendell A. Lim "Engineering modular protein interaction switches by sequence overlap" Journal of the American Chemical Society, v.129, 2007, p..

McBeth C, Seamons A, Pizarro JC, Fleishman SJ, Baker D, Kortemme T, Goverman JM, Strong RK. "A new twist in TCR diversity revealed by a forbidden alphabeta TCR." J Mol Biol., v.375(5), 2008, p.1306.

Hu JC, Aramayo R, Bolser D, Conway T, Elsik CG, Gribskov M, Kelder T, Kihara D, Knight TF Jr, Pico AR, Siegele DA, Wanne. "The emerging world of wikis." Science., v.320, 2008, p.1289.

Tabor JJ, Salis HM, Simpson ZB, Chevalier AA, Levskaya A, et al. "A synthetic genetic edge detection program." Cell 137, v., 2009, p.1272-1281.

Endy, D. "Genomics. Reconstruction of the genomes." Science., v.319(586, 2008, p.1196.

Tang YJ, Martin HG, Dehal PS, Deutschbauer A, Llora X, et al. "Metabolic flux analysis of Shewanella spp. reveals evolutionary robustness in central carbon metabolism." Biotechnol Bioeng 102, v., 2009, p.1161-1169.

Wellhausen R, Mukunda G "Aspects of the political economy of development and synthetic biology" Syst Synth Biol 3, v., 2009, p.115-123.

Skerker J, Lucks J, Arkin A "Evolution, ecology and the engineered organism: lessons for synthetic biology." Genome Biology 10, v., 2009, p.114.

Bennett G, Gilman N, Stavrianakis A, Rabinow P "From synthetic biology to biohacking: are we prepared?" Nat Biotechnol 27, v., 2009, p.1109-1111.

Yadav SS, Yeh BJ, Craddock BP, Lim WA, Miller WT "Reengineering the signaling properties of a Src family kinase." Biochemistry 48, v., 2009, p.10956-109.

Good M, Tang G, Singleton J, Remenyi A, Lim WA "The Ste5 scaffold directs mating signaling by catalytically unlocking the Fus3 MAP kinase for activation." Cell 136, v., 2009, p.1085-1097.

Sallee NA, Rivera GM, Dueber JE, Vasilescu D, Mullins RD, Mayer BJ, Lim WA. "The pathogen protein EspF(U) hijacks actin polymerization using mimicry and multivalency." Nature., v.454, 2008, p.1005.

Dantas G, Sommer MO, Oluwasegun RD, Church GM. "Bacteria susbsisting on antibiotics." Science., v.320(587, 2008, p.100.

John E. Dueber, Ethan A. Mirsky, and Wendell A. Lim "Engineering synthetic signaling proteins with ultrasensitive input/output control" Nature Biotechnology, v.25, 2007, p..

Hans Bugl, John P Danner, Robert J Molinari, John T Mulligan, Han-Oh Park, Bas Reichert, David A Roth, Ralf Wagner, Bruce Budowle, Robert M Scripp, Jenifer A L Smith, Scott J Steele, George Church & Drew Endy "DNA synthesis and biological security" Nature Biotechnology, v.25, 2007, p..

Beltrao P, Trinidad JC, Fiedler D, Roguev A, Lim WA, et al. "Evolution of phosphoregulation: comparison of phosphorylation patterns across yeast species." PLoS Biol 7, v., 2009, p.e1000134.

Burnett JC, Miller-Jensen K, Shah PS, Arkin AP, Schaffer DV "Control of stochastic gene expression by host factors at the HIV promoter." PLoS Pathog 5, v., 2009, p.e1000260.

Lee JH, Park IH, Gao Y, Li JB, Li Z, et al. "A robust approach to identifying tissue-specific gene expression regulatory variants using personalized human induced pluripotent stem cells." PLoS Genet 5, v., 2009, p.e1000718.

Forster AC, Church GM. "Synthetic biology projects in vitro" Genome Research, v.17, 2007, p..

Douglas J. Pitera, Chris J. Paddon, Jack D. Newman, Jay D. Keasling "Balancing a heterologous mevalonate pathway for improved isoprenoid production in Escherichia coli" Metabolic Engineering, v.9, 2007, p..

Novichkov PS, Laikova ON, Novichkova ES, Gelfand MS, Arkin AP, et al. "RegPrecise: a database of curated genomic inferences of transcriptional regulatory interactions in prokaryotes." Nucleic Acids Res 38, v., 2010, p.D111-118.

Levskaya A, Weiner OD, Lim WA, Voigt CA "Spatiotemporal control of cell signalling using a light-switchable protein interaction." Nature 461, v., 2009, p.997-1001.

Rabinow P, Bennett G "Synthetic biology: ethical ramifications 2009." Syst Synth Biol 3, v., 2009, p.99-108.

Ouellet M, Adams PD, Keasling JD, Mukhopadhyay A "A rapid and inexpensive labeling method for microarray gene expression analysis." BMC Biotechnol 9, v., 2009, p.97.

Oye KA "Future Imperfect: Technology and Freedom in an Uncertain World." Issues in Science and Technology 26, v., 2009, p.91-93.

Lee PJ, Helman NC, Lim WA, Hung PJ. "A microfluidic system for dynamic yeast cell imaging." Biotechniques., v.44(1), 2008, p.91.

Wang HH, Isaacs FJ, Carr PA, Sun ZZ, Xu G, et al. "Programming cells by multiplex genome engineering and accelerated evolution." Nature 460, v., 2009, p.894-898.

Stolyar S, He Q, Joachimiak MP, He Z, Yang ZK, Borglin SE, Joyner DC, Huang K, Alm E, Hazen TC, Zhou J, Wall JD, Arkin A. "Response of Desulfovibrio vulgaris to alkaline stress." J Bacteriol., v.189, 2008, p.8944.

Ro DK, Ouellet M, Paradise EM, Burd H, Eng D, Paddon CJ, Newman JD, Keasling JD. "Induction of multiple pleiotropic drug resistance genes in yeast engineered to produce an increased level of anti-malari." BMC Biotechnol., v.8, 2008, p.83.

Nielsen DR, Prather KJ "In situ product recovery of n-butanol using polymeric resins." Biotechnol Bioeng 102, v., 2009, p.811-821.

Bower DM, Prather KL "Engineering of bacterial strains and vectors for the production of plasmid DNA." Appl Microbiol Biotechnol 82, v., 2009, p.805-813.

King N, Westbrook MJ, Young SL, Kuo A, Abedin M, Chapman J, Fairclough S, Hellsten U, Isogai Y, Letunic I, Marr M, Pincu. "The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans." Nature., v.451(718, 2008, p.783.

Arkin, A. "Setting the standard in synthetic biology." Nat Biotechnol., v.26, 2008, p.771.

Ma W, Trusina A, El-Samad H, Lim WA, Tang C "Defining network topologies that can achieve biochemical adaptation." Cell 138, v., 2009, p.760-773.

Dueber JE, Wu GC, Malmirchegini GR, Moon TS, Petzold CJ, et al. "Synthetic protein scaffolds provide modular control over metabolic flux." Nat Biotechnol 27, v., 2009, p.753-759.

Smith, CA; Kortemme, T. "Backrub-Like Backbone Simulation Recapitulates Natural Protein Conformational Variability and Improves Mutant Side-Chain." J Mol Biol., v.380(4), 2008, p.742.

Cecconi C, Shank EA, Dahlquist FW, Marqusee S, Bustamante C. "Protein-DNA chimeras for single molecule mechanical folding studies with the optical tweezers." Eur Biophys J., v.37, 2008, p.729.

Leonard E, Nielsen D, Solomon K, Prather KJ. "Engineering microbes with synthetic biology frameworks." Trends Biotechnology, v.12, 2008, p.674.

Leonard E, Nielsen D, Solomon K, Prather KJ "Engineering microbes with synthetic biology frameworks." Trends Biotechnol 26, v., 2008, p.674-681.

Kirby J, Keasling JD. "Metabolic engineering of microorganisms for isoprenoid production." Nat Prod Rep., v.25(4), 2008, p.656.

Bayer TS, Widmaier DM, Temme K, Mirsky EA, Santi DV, et al. "Synthesis of methyl halides from biomass using engineered microbes." J Am Chem Soc 131, v., 2009, p.6508-6515.

Bischofs IB, Hug JA, Liu AW, Wolf DM, Arkin AP "Complexity in bacterial cell-cell communication: quorum signal integration and subpopulation signaling in the Bacillus subtilis phosphorelay." Proc Natl Acad Sci U S A 106, v., 2009, p.6459-6464.

Ross J, Arkin AP "Complex systems: from chemistry to systems biology." Proc Natl Acad Sci U S A 106, v., 2009, p.6433-6434.

Czar MJ, Anderson JC, Bader JS, Peccoud J "Gene synthesis demystified." Trends Biotechnol 27, v., 2009, p.63-72.

Martin CH, Prather KLJ "High-titer production of monomeric hydroxyvalerates from levulinic acid in Pseudomonas putida." Journal of Biotechnology 139, v., 2009, p.61-67.

Yoshikuni Y, Dietrich JA, Nowroozi FF, Babbitt PC, Keasling JD. "Redesigning enzymes based on adaptive evolution for optimal function in synthetic metabolic pathways." Chem Biol., v.15, 2008, p.607.

McIver AM, Garikipati SV, Bankole KS, Gyamerah M, Peeples TL. "Microbial oxidation of naphthalene to cis-1,2-naphthalene dihydrodiol using naphthalene dioxygenase in biphasic media." Biotechnol Prog., v.24(3), 2008, p.593.

Moon TS, Yoon SH, Lanza AM, Roy-Mayhew JD, Prather KL "Production of glucaric acid from a synthetic pathway in recombinant Escherichia coli." Appl Environ Microbiol 75, v., 2009, p.589-595.

Lee SK, Chou H, Ham TS, Lee TS, Keasling JD "Metabolic engineering of microorganisms for biofuels production: from bugs to synthetic biology to fuels." Curr Opin Biotechnol 19, v., 2008, p.556-563.

Rivera GM, Vasilescu D, Papayannopoulos V, Lim WA, Mayer BJ "A reciprocal interdependence between Nck and PI(4,5)P(2) promotes localized N-WASp-mediated actin polymerization in living cells." Mol Cell 36, v., 2009, p.525-535.

Oliveira PH, Prather KJ, Prazeres DM, Monteiro GA "Structural instability of plasmid biopharmaceuticals: challenges and implications." Trends Biotechnol 27, v., 2009, p.503-511.

Shetty RP, Endy D, Knight TF Jr. "Engineering BioBrick vectors from BioBrick parts." J Biol Eng., v.2(1), 2008, p.5.

Carothers JM, Goler JA, Keasling JD "Chemical synthesis using synthetic biology." Curr Opin Biotechnol 20, v., 2009, p.498-503.

Kosuri S, Kelly JR, Endy D. "TABASCO: A single molecule, base-pair resolved gene expression simulator." BMC Bioinformatics., v.8, 2007, p.480.

Paul Rabinow GB, Anthony Stavrianakis "Prosperity, Amelioration, Flourishing: From a Logic of Practical Judgment to Reconstruction - An Account of his Work with SynBERC." Law & Literature 21, v., 2009, p.471-479.

Temme K, Salis H, Tullman-Ercek D, Levskaya A, Hong SH, Voigt CA. "Induction and relaxation dynamics of the regulatory network controlling the type III secretion system encoded within Sal." J Mol Biol., v.377(1), 2008, p.47.

Prather KL, Martin CH. "De novo biosynthetic pathways: rational design of microbial chemical factories." Curr Opin Biotechnol., v.19, 2008, p.468.

Weiss R, Panke S "Synthetic biology-paths to moving forward." Curr Opin Biotechnol 20, v., 2009, p.447-448.

Purnick PE, Weiss R "The second wave of synthetic biology: from modules to systems." Nat Rev Mol Cell Biol 10, v., 2009, p.410-422.

Kelly J, Rubin A, Davis J, Ajo-Franklin C, Cumbers J, et al. "Measuring the activity of BioBrick promoters using an in vivo reference standard." Journal of Biological Engineering 3, v., 2009, p.4.

Groban ES, Clarke EJ, Salis HM, Miller SM, Voigt CA "Kinetic buffering of cross talk between bacterial two-component sensors." J Mol Biol 390, v., 2009, p.380-393.

Fortman JL, Chhabra S, Mukhopadhyay A, Chou H, Lee TS, Steen E, Keasling JD. "Biofuel alternatives to ethanol: pumping the microbial well." Trends Biotechnol., v.26(7), 2008, p.375.

Bang D, Church GM. "Gene synthesis by circular assembly amplification." Nat Methods., v.5(1), 2008, p.37.

Zeke A, Lukacs M, Lim WA, Remenyi A "Scaffolds: interaction platforms for cellular signalling circuits." Trends Cell Biol 19, v., 2009, p.364-374.

Garfinkel MS, Endy D, Epstein GL, Friedman RM. "Synthetic genomics - options for governance." Biosecur Bioterror., v.5(4), 2007, p.359.

Kizer L, Pitera DJ, Pfleger BF, Keasling JD. "Application of functional genomics to pathway optimization for increased isoprenoid production." Appl Environ Microbiol., v.74(10), 2008, p.3229.

Norville JE, Kelly DF, Knight TF Jr, Belcher AM, Walz T. "7A projection map of the S-layer protein sbpA obtained with trehalose-embedded monolayer crystals." J Struct Biol., v.160(3), 2007, p.313.

Tseng HC, Martin CH, Nielsen DR, Prather KL "Metabolic engineering of Escherichia coli for enhanced production of (R)- and (S)-3-hydroxybutyrate." Appl Environ Microbiol 75, v., 2009, p.3137-3145.

Baidoo EE, Benke PI, Neusüss C, Pelzing M, Kruppa G, Leary JA, Keasling JD. "Capillary electrophoresisfourier transform ion cyclotron resonance mass spectrometry for the identification of cationic." Anal Chem., v.801(9), 2008, p.3112.

Keasling JD, Chou H. "Metabolic engineering delivers next-generation biofuels." Nat Biotechnol., v.23(6), 2008, p.298.

Lun DS, Rockwell G, Guido NJ, Baym M, Kelner JA, et al. "Large-scale identification of genetic design strategies using local search." Mol Syst Biol 5, v., 2009, p.296.

Leonard E, Runguphan W, O'Connor S, Prather KJ "Opportunities in metabolic engineering to facilitate scalable alkaloid production." Nat Chem Biol 5, v., 2009, p.292-300.

Martin CH, Nielsen DR, Solomon KV, Prather KL "Synthetic metabolism: engineering biology at the protein and pathway scales." Chem Biol 16, v., 2009, p.277-286.

Chivian D, Brodie EL, Alm EJ, Culley DE, Dehal PS, Desantis TZ, Gihring TM, Lapidus A, Lin LH, Lowry SR, Moser DP, Richa "Environmental genomics reveals a single-species ecosystem deep within Earth." Science., v.322, 2008, p.275.

Voigt CA. "Life from information." Nat Methods., v.5(1), 2008, p.27.

Dietrich JA, Yoshikuni Y, Fisher KJ, Woolard FX, Ockey D, et al. "A novel semi-biosynthetic route for artemisinin production using engineered substrate-promiscuous P450(BM3)." ACS Chem Biol 4, v., 2009, p.261-267.

Nielsen DR, Leonard E, Yoon SH, Tseng HC, Yuan C, et al. "Engineering alternative butanol production platforms in heterologous bacteria." Metabolic Engineering 11, v., 2009, p.262-273.

Lucks JB, Qi L, Whitaker WR, Arkin AP "Toward scalable parts families for predictable design of biological circuits." Current Opinion in Microbiology 11, v., 2008, p.567-573.

David Baker, George Church, Jim Collins, Drew Endy, Joe Jacobson, Jay Keasling, Paul Modrich, Christina Smolke, Ron Weiss "Building a fab for biology" Scientific American, v.294, 2006, p..

Brian F. Pfleger, Douglas J. Pitera,1, Jack D. Newman, Vincent J.J. Martina, Jay D. Keasling "Microbial sensors for small molecules: Development of a mevalonate biosensor" Metabolic Engineering, v.9, 2007, p..

Brian J. Yeh, Robert J. Rutigliano, Anrica Deb, Dafna Bar-Sagi, and Wendell A. Lim "Rewiring cellular morphology pathways with synthetic guanine nucleotide exchange factors" Nature, v.447, 2007, p..

Arkin AP, Fletcher DA "Fast, cheap, and somewhat in control" Genome Biology, v.7, 2007, p..

Andrews SS, Arkin AP "Systems biology: a switch for sex" Current Biology, v.17, 2007, p..

Keasling JD "Synthetic biology for synthetic chemistry" ACS Chem Biol, v., 2008, p..

H. Salis, A. Tamsir, C.A. Voigt. "Engineering Bacterial Signals and Sensors." Bacterial sensing and signaling (book), v., 2008, p..

Lee S, Dudley, A., Drubin, D., Ludlow, C., Shales, M., Silver, PA., Krogan, NJ, Peâ??er, D. and Koller, D. "Analysis of individual expression variation reveals a post-transcriptional network." PLoS Genet., v., 2009, p..

Yoon SH, Park HM, Kim JE, Lee SH, Choi MS, Kim JY, Oh DK, Keasling JD, Kim SW "Increased beta-carotene production in recombinant Escherichia coli harboring an engineered isoprenoid precursor pathway with mevalonate addition." Biotechnol Prog., v., 2007, p..

Yoshikuni Y, Keasling JD. "Pathway engineering by designed divergent evolution." Nature., v., 2007, p..

Yeh BJ, Lim WA "Synthetic biology: lessons from the history of synthetic organic chemistry" Nat Chem Biol., v., 2007, p..

Yeh BJ, Rutigliano RJ, Deb A, Bar-Sagi D, Lim WA "Rewiring cellular morphology pathways with synthetic guanine nucleotide exchange factors" Nature., v., 2007, p..

Voigt CA "Life from information." Nat Methods., v., 2008, p..

Voigt CA. "Genetic parts to program bacteria." Curr Opin Biotechnol., v., 2006, p..

Waks Z, Silver PA "Engineering a synthetic dual-organism system for hydrogen production." Appl Environ Microbiol 75, v.1867-18, 2009, p..

Withers ST, Gottlieb SS, Lieu B, Newman JD, Keasling JD "Identification of isopentenol biosynthetic genes from Bacillus subtilis by a screening method based on isoprenoid precursor toxicity." Appl Environ Microbiol, v., 2007, p..

Wolf DM, Fontaine-Bodin L, Bischofs I, Price G, Keasling J, Arkin AP. "Memory in microbes: quantifying history-dependent behavior in a bacterium." PLoS ONE., v., 2008, p..

Vigneault F, Sismour AM, Church GM. "Efficient microRNA capture and bar-coding via enzymatic oligonucleotide adenylation." Nat Methods., v., 2008, p..

Suthers PF, Burgard AP, Dasika MS, Nowroozi F, Van Dien S, Keasling JD, Maranas "Metabolic flux elucidation for large-scale models using 13C labeled isotopes" Metab, v., 2007, p..

Shui W, Sheu L, Liu J, Smart B, Petzold CJ, Hsieh TY, Pitcher A, Keasling JD, Bertozzi CR. "Membrane proteomics of phagosomes suggests a connection to autophagy." Proc Natl Acad Sci U S A., v.105, 2008, p..

Steen EJ, Chan R, Prasad N, Myers S, Petzold CJ, et al. "Metabolic engineering of Saccharomyces cerevisiae for the production of n-butanol." Microb Cell Fact 7, v.36, 2008, p..

Sallee NA, Yeh BJ, Lim WA "Engineering modular protein interaction switches by sequence overlap" J Am Chem Soc., v., 2007, p..

Samoilov MS, Arkin AP. "Deviant effects in molecular reaction pathways." Nat Biotechnol., v., 2006, p..

Samoilov MS, Price G, Arkin AP. "From fluctuations to phenotypes: the physiology of noise" Sci STKE., v., 2006, p..

Rodrigo G, Carrera J, Prather KJ, Jaramillo A. "DESHARKY: automatic design of metabolic pathways for optimal cell growth." Bioinformatics., v.24, 2008, p..

Prather KLJ, Jaramillo A "Editorial: Focus on synthetic biology." Biotechnology Journal 4, v.1367, 2009, p..

Price MN, Dehal PS, Arkin AP "Horizontal gene transfer and the evolution of transcriptional regulation in Escherichia coli." Genome Biol, v., 2008, p..

Pincus D, Letunic I, Bork P, Lim WA. "Evolution of the phospho-tyrosine signaling machinery in premetazoan lineages." Proc Natl Acad Sci U S A., v.105, 2008, p..

Pitera DJ, Paddon CJ, Newman JD, Keasling JD. "Balancing a heterologous mevalonate pathway for improved isoprenoid production in Escherichia coli." Metab Eng., v., 2007, p..

Paradise EM, Kirby J, Chan R, Keasling JD "Redirection of flux through the FPP branchpoint in Saccharomyces cerevisiae by downregulating squalene synthase." Biotechnol, v., 2008, p..

Paradise EM, Kirby J, Chan R, Keasling JD. "Redirection of flux through the FPP branch-point in Saccharomyces cerevisiae by downregulating squalene synthase." Biotechnol Bioeng., v., 2008, p..

Natalie Kuldell. "Authentic teaching and learning through synthetic biology." J Biol Eng., v.1(1), 2007, p..

Martin CH, Prather KL. "High-titer production of monomeric hydroxyvalerates from levulinic acid in Pseudomonas putida." J Biotechnol., v., 2008, p..

Lee SK, Chou H, Ham TS, Lee TS, Keasling JD. "Metabolic engineering of microorganisms for biofuels production: from bugs to synthetic biology to fuels." Curr Opin Biotechnol., v., 2008, p..

Lee SK, Chou HH, Pfleger BF, Newman JD, Yoshikuni Y, Keasling JD "Directed evolution of AraC for improved compatibility of arabinose- and lactose-inducible promoters" Appl Environ Microbiol, v., 2007, p..

Lubertozzi D, Keasling JD. "Developing Aspergillus as a host for heterologous expression." Biotechnol Adv., v., 2008, p..

Lubertozzi D, Keasling JD. "Expression of a synthetic Artemesia annua amorphadiene synthase in Aspergillus nidulans yields altered product distribut." J Ind Microbiol Biotechnol., v.35, 2008, p..

Lucks JB, Qi L, Whitaker WR, Arkin AP. "Toward scalable parts families for predictable design of biological circuits." Curr Opin Microbiol., v., 2008, p..

Lauffer BE, Chen S, Melero C, Kortemme T, von Zastrow M, Vargas GA. "Engineered protein connectivity to actin mimics PDZ-dependent recycling of GPCRS but not its regulation by HRS." J Biol Chem., v., 2008, p..

Karsten Temme, Howard Salis, Danielle Tullman-Ercek, Anselm Levskaya, Soon-Ho Hone, and Christopher A. Voigt. "Induction and relaxation dynamics of the regulatory network controlling the type III secretion system encoded within Sal." Journal of Molecular Biology, v., 2008, p..

Kazakov AE, Rodionov DA, Alm E, Arkin AP, Dubchak I, Gelfand MS. "Comparative Genomics of Regulation of Fatty Acid and Branched-chain Amino Acid Utilization in Proteobacteria." J Bacteriol., v., 2008, p..

Keasling, JD. "Synthetic biology for synthetic chemistry." ACS Chem Biol., v., 2008, p..

Kenneth A. Oye RW "The Intellectual Commons and Property in Synthetic Biology." In: Schmidt M, editor. Synthetic biology: The technoscience and its societal consequences., v., 2009, p..

Kirby J, Keasling JD "Biosynthesis of plant isoprenoids: perspectives for microbial engineering." Annu Rev Plant Biol 60, v.335-355, 2009, p..

Kosuri S, Kelly JR, Endy D "TABASCO: A single molecule, base-pair resolved gene expression simulator" BMC Bioinformatics, v., 2007, p..

Kuldell N In: Amos M, editor "Genome Refactoring" Synthesis Lectures on Synthetic Biology: Morgan Claypool., v., 2009, p..

Jeng ES, Nelson JD, Prather KLJ, Strano MS "Detection of a Single Nucleotide Polymorphism Using Single-Walled Carbon-Nanotube Near-Infrared Fluorescence13" Small 6, v.40-43, 2010, p..

K. Temme, H. Salis, D. Tullman-Ercek, A. Levskaya, S.H. Hong, C.A. Voigt. "Induction and relaxation dynamics of the regulatory network controlling the type III secretion system encoded within Sal." Journal of Molecular Biology, v., 2008, p..

Humphris EL, Kortemme T. "Design of multi-specificity in protein interfaces." PLoS Comput Biol., v., 2007, p..

Guo J, Wang J, Anderson JC, Schultz PG "Addition of an alpha-hydroxy acid to the genetic code of bacteria." Angew Chem Int Ed Engl, v., 2008, p..

Ham TS, Lee SK, Keasling JD, Arkin AP. "Design and construction of a double inversion recombination switch for heritable sequential genetic memory." PLoS ONE., v.3, 2008, p..

Flaherty P, Radhakrishnan ML, Dinh T, Rebres RA, Roach TI, Jordan MI, Arkin AP. "A dual receptor crosstalk model of g-protein-coupled signal transduction." PLoS Comput Biol., v., 2008, p..

Forster AC, Church GM. "Towards synthesis of a minimal cell." Mol Syst Biol., v., 2006, p..

Friedland GD, Linares AJ, Smith CA, Kortemme T. "A simple model of backbone flexibility improves modeling of side-chain conformational variability." J Mol Biol., v., 2008, p..

Fuller CW, Middendorf LR, Benner SA, Church GM, Harris T, et al. "The challenges of sequencing by synthesis." Curr Opin Biotechnol 20, v.1013-10, 2009, p..

Garfinkel MS, Endy D, Epstein GL, Friedman RM "Synthetic genomics | options for governance" Biosecur Bioterror, v., 2007, p..

Dueber JE, Mirsky EA, Lim WA. "Engineering synthetic signaling proteins with ultrasensitive input/output control." Nat Biotechnol., v., 2007, p..

Farny NG, Kedersha NL, Silver PA "Metazoan stress granule assembly is mediated by P-eIF2alpha-dependent and -independent mechanisms." RNA 15, v.1814-18, 2009, p..

Eames M, Kortemme T. "Structural mapping of protein interactions reveals differences in evolutionary pressures correlated to mRNA level and protein abundance" Structure., v., 2007, p..

Douglas Densmore, J. Christopher Anderson. "Combinational Logic Design in Synthetic Biology." Proceedings of the IEEE, v., 2008, p..

Czar, M. J., Anderson, J. C., Bader, J. S., Peccoud, J. "Gene synthesis demystified." Trends in Biotechnology, v., 2008, p..

Bügl H, Danner JP, Molinari RJ, Mulligan JT, Park HO, Reichert B, Roth DA, Wagner R., Budowle B, Scripp RM, Smith JA, Steele SJ, Church G, Endy D. "DNA synthesis and biological security" Nat Biotechnol., v., 2007, p..

Canton B, Labno A, Endy D. "Refinement and standardization of synthetic biological parts and devices." Nat Biotechnol., v.787, 2008, p..

Bang D, Church GM "Gene synthesis by circular assembly amplification" Nat Methods, v., 2008, p..

Blanch HW, Adams PD, Andrews-Cramer KM, Frommer WB, Simmons BA, Keasling "Addressing the need for alternative transportation fuels: the Joint BioEnergy Institute" ACS Chem Biol, v., 2008, p..

Blanch HW, Adams PD, Andrews-Cramer KM, Frommer WB, Simmons BA, Keasling JD. "Addressing the need for alternative transportation fuels: the Joint BioEnergy Institute." ACS Chem Biol., v., 2008, p..

Anderson JC, Voigt CA, Arkin AP "Environmental signal integration by a modular AND gate" Mol Syst Biol., v., 2007, p..

Andrews SS, Arkin AP. "Simulating cell biology." Curr Biol., v., 2006, p..

Andrews, S. S., et al. "Stochastic modeling of biochemical reaction networks." Encyclopedia of Complexity and System Science., v., 2008, p..

Apgar JF, Toettcher JE, Endy D, White FM, Tidor B. "Stimulus design for model selection and validation in cell signaling." PLoS Comput Biol., v.4(2), 2008, p..

Price MN, Dehal PS, Arkin AP. "Horizontal gene transfer and the evolution of transcriptional regulation in Escherichia coli." Genome Biol., v., 2008, p..

Tang YJ, Sapra R, Joyner D, Hazen TC, Myers S, Reichmuth D, Blanch H, Keasling JD. "Analysis of metabolic pathways and fluxes in a newly discovered thermophilic and ethanol-tolerant Geobacillus strain." Biotechnol Bioeng., v., 2008, p..

Hurt JA, Obar RA, Zhai B, Farny NG, Gygi SP, et al. "A conserved CCCH-type zinc finger protein regulates mRNA nuclear adenylation and export." J Cell Biol 185, v.265-277, 2009, p..

Yoichiro Shiba, Eric M. Paradise, James Kirby, Dae-Kyun Rob, Jay D. Keasling "Engineering of the pyruvate dehydrogenase bypass in Saccharomyces cerevisiae for high-level production of isoprenoids" Metabolic Engineering, v.9, 2007, p..

Martin L, Che A, Endy D "Gemini, a bifunctional enzymatic and fluorescent reporter of gene expression." PLoS One 4, v., 2009, p.e7569.

Tsuruta H, Paddon CJ, Eng D, Lenihan JR, Horning T, et al. "High-level production of amorpha-4,11-diene, a precursor of the antimalarial agent artemisinin, in Escherichia coli." PLoS One 4, v., 2009, p.e4489.


Project Outcomes Report

Disclaimer

This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.

Intellectual Merit

Synberc has defined Synthetic Biology as the design of novel - or the redesign of existing -biological systems for the purpose of producing outcomes that benefit society.  Examples of successful outcomes include microbes that sustainably produce biofuels or bio-based chemicals to replace those currently sourced from fossil fuels, or that produce new and inexpensive pharmaceuticals to combat current and emerging diseases, or microbes that can detect and destroy toxic chemical agents, or remediate polluted sites.  Beyond microbes, Synberc’s vision also includes pest resistant crops such as corn or soybeans that can fix atmospheric nitrogen so that they can grow in the absence of added fertilizers, and culturable human cells and organs that can be used to test the efficacy and safety of drugs and drug candidates in vitro, obviating the need for large scale animal testing.    Bio-based fuels or chemicals are generated from networks of enzymes that together produce a biosynthetic pathway.  Similarly, remediation or drug screening is also dependent on enzymes.  Enzymes are produced biologically from specific genes.  In most instances, therefore, successful outcomes will depend on assembling, in a desired host cell, a large network of synthetic or naturally occurring genes that may originate in different organisms, and designing systems to precisely control the expression of these genes so that the titers of the desired product, or the required internal enzyme levels for remediation or drug screening, will be predictably and reliably achieved.

By nature, biological systems are complex and unpredictable.  Over the years, however, microorganisms have been engineered to produce ethanol, or valuable drugs, or detect and degrade nerve agents, etc., but these biological engineering challenges have required long development times due, in large part, to our poor understanding of biological systems and to a lack of useful tools that would enable engineers to easily and predictably reprogram existing systems, as well as to build new enzymes, genetic circuits, and, eventually, whole cells.  Just as engineers use standardized parts and devices to build integrated circuits to achieve reliable output, Synberc embarked on the standardization of biological parts (genes), and devices (genes and their regulatory components), and their assembly into genetic circuits and networks to reduce the complexity of biological systems to achieve predictable and reliable research outcomes. 

Broader Impacts

Understanding the risks that could be imposed through potential misuse of synthetic biology, Synberc developed a Human Practices component to both study issues related to safety and security.  We created an outreach program to engage with the public to provide awareness of the benefits and risks of this emerging technology and a diversity and inclusion program to encourage kindergarten through college level students to enter STEM fields.  We created both an Industrial Advisory Board composed of biotechnology companies, which grew to more than 40 members, as well as a Scientific and Strategic Advisory Board composed of experts in biology, chemistry, social sciences and security to provide input and guidance of our diverse research and communications agenda.   Starting in 206 with the assemblage of 10 leading investigators from five universities in the US, by 2016, this effort had grown to more than 500 people including 34 faculty members, their postdoctoral fellows, graduate students and undergraduates from more than 30 institutions.  Beyond actual participants in Synberc, through teacher and student training, IGEM (International Genetically Engineered Machines) competitions, and public forums and outreach, we have reached hundreds of thousands of people in the US and internationally, and created a new and exciting field that merges biology, chemistry, and engineering.  In its 10 year life-span, Synberc evolved into a premiere venue for the research community for exchanging ideas; providing a repository basic biological components; and implementing an organizing framework in which to develop specific applications. Synberc’s efforts add value by leading to new synergies, and our collaborative efforts have achieved what could not be accomplished through a narrow or individual approach.


Last Modified: 03/28/2017
Modified by: Jay D Keasling

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