20.20(S10):Advanced topics

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20.385: Advanced Topics in Synthetic Biology


Homework dropbox is here

Part 1: Readings

  • Paper 1 (10%): presented with a partner
  • Paper 2 (15%): presented solo
  • Response record (25%): your thoughts about the papers you don't present.

Instructions for these assignment are here

Part 2: Team Mentoring

  • Progress reports (15%): one page summaries of your freshman team's work
  • Mentoring journal(15%): one page summary of your freshman team's dynamics
  • Team's project average (15%): based on the grade for the 3 major assignments submitted by your freshman team
  • Instructor Leverage (5%): discretionary adjustment by NK

Instructions for these assignments are here

Reading Schedule

Discussions will be 1 hour long during Wednesday 2-5 studio block


TOPIC DATE Discussion leader(s) Discussion paper(s) Related paper(s) to enjoy
Preview of 20.385 Wed Feb 3 Natalie Kuldell
Ron Weiss
before next week read
  1. Sci Am summary (handout)
  2. Two ‘What if” experiments
    Ptashne, M.
    PMID: 15055587
  3. Build Artificial
    Brent, R.
    PMID: 15055588
Parts™ Wed Feb 10 Natalie Kuldell
Ron Weiss
A eukaryotic transcriptional activator bearing the DNA specificity of a prokaryotic repressor.

Brent R, Ptashne M.Cell. 1985 Dec;43(3 Pt 2):729-36.
PMID: 3907859

Activation of prokaryotic transcription through arbitrary protein-protein contacts
Dove SL, et al.
Nature. 1997 Apr 10;386(6625):627-30.
PMID: 9121589
Logic Modules
Wed Feb 17 (RW OoT) Environmental signal integration by a modular AND gate.
Anderson JC, Voigt C, Arkin, AP Molecular systems biology3 133 2007
DOI : 10.1038/msb4100173
A synthetic oscillatory network of transcriptional regulators.
Elowitz, MB, and Leibler, S. Nature 403,

335–338 (2000)
Construction of a genetic toggle switch in Escherichia coli
Gardner TS, et al.Nature 403, 339–342 (2000)
May also want non-DNA, non-protein based logic paper (RNAi logic?)

Signal Specificity
Wed Feb 24 Rewiring the specificity of two-component signal transduction systems.
Skerker JM, et al. Cell (2008)133(6):1043-54.
DOI: 10.1016/j.cell.2008.04.040
Synthetic biology: engineering Escherichia coli to see light.
Levskaya A, et al.
PMID: 16306980
Controlling System Dynamics
Wed Mar 3 (RW OoT) Using Engineered Scaffold Interactions to Reshape MAP Kinase Pathway Signaling Dynamics
Bashor CJ, et al. Science (2008)319: 1539-1543
DOI: 10.1126/science.1151153
Synthetic protein scaffolds provide modular control over metabolic flux.
Dueber JE, et al.
PMID: 19648908
Functional Network Composition
Thursday Mar 11 Diversity-based, model-guided construction of synthetic gene networks with predicted functions
Ellis T, Wang X, and Collins JJ. Nat Biotech
A synthetic genetic edge detection program
Tabor JJ et al.
PMID: 19563759
Tuning the system: directed evolution
Wed Mar 17 A fast, robust and tunable synthetic gene oscillator
Stricker, J. et al. Nature 456, 516–519 (2008).
Directed evolution of a genetic circuit
Yokobayashi, Y, et al.Proc. Natl Acad. Sci. USA 99, 16587–16591 (2002).
Spring Break Mar 22-26 No class all week
DNA construction and editing technologies
Wed Mar 31 Article 1:
Programming cells by multiplex genome engineering and accelerated evolution.
Wang HH, et al. Nature 2009 Aug 13;460(7257):894-8.
Article 2:
Complete chemical synthesis, assembly, and cloning of a Mycoplasma genitalium genome.Gibson DG, et al. Science. 2008 Feb 29;319(5867):1215-20.
PMID: 18218864
Stemmer WP, et al. Single-step assembly of a gene and entire plasmid from large numbers of oligodeoxyribonucleotides.

PMID: 7590320

Thursday Apr 8 Article 1: Towards synthesis of a minimal cell
Forster, A. C. & Church, G. M.
Mol. Syst. Biol. 2, 45 (2006)
alternative Article 1? Emergent properties of reduced-genome Escherichia coli.
Pósfai G, et al. Science.(2006)312(5776):1044-6.
PMID: 16645050
Article 2: Genome transplantation in bacteria:

changing one species to another.
Lartigue C, et al. Science 2007, 317:632-638.

Reconstitution of contractile FtsZ rings in liposomes. Osawa M, Anderson DE, Erickson HP.Science (2008)320(5877):792-4.
DOI: 10.1126/science.1154520
In silico and -omics
Wed Apr 14 'Article 1: Design of genetic networks with specified functions by evolution in silico
Francois, P. & Hakim, V.
Proc. Natl Acad. Sci. USA 101, 580–585 (2004).
Article 2:'Engineering transcription factors with novel DNA-binding specificity using comparative genomics
Desai TA, et al. Nucleic Acids Res 2009
Design of multi-specificity in protein interfacesHumphris, EL; Kortemme, T. PLoS computational biology (2007) 3(8):e164
DOI : 10.1371/journal.pcbi.0030164
Wed Apr 21 Article 1: Gene regulation at the single-cell level
Rosenfeld N, et al. Science 307, 1962–1965 (2005).
Article 2: Stochastic switching as a survival strategy in fluctuating environments.
Acar M. et al. Nature Genetics 40, 471 – 475 (2008)
Phenotypic consequences of promoter-mediated transcriptional noise.
Blake WJ, et al. Molecular Cell(2006) 24(6):853-65
DOI : 10.1016/j.molcel.2006.11.003
Metabolic Engineering Wed Apr 28 Article 1: Production of the antimalarial drug precursor artemisinic acid in engineered yeast
Ro DK, et al. Nature (2006) 440, 940–943
PMID: 16612385
Article 2: Synthesis of methyl halides from biomass using engineered microbes
Bayer TS, et al. J Am Chem Soc 2009, 131:6508-6515.
PMID: 19378995
Cell Cell Communication/System Ecology Tue May 4 Article 1: A synthetic Escherichia coli predator-prey ecosystem
Balagaddé FK, et al. Mol Syst Biol. 2008;4:187.
PMID: 18414488 Article 2: Synthetic ecosystems based on airborne inter- and intrakingdom communication
Weber, W., Daoud-El Baba, M. & Fussenegger, M. Proc. Natl Acad. Sci. USA (2007) 104, 10435–10440
PMID: 17551014
Synthetic cooperation in engineered yeast populations
Shou W, Ram S, Vilar JM. Proc Natl Acad Sci U S A. (2007) Feb 6;104(6):1877-82.
PMID: 17267602
Property rights in synthetic biology Tue May 11? Article 1: Synthetic biology: caught between property rights, the public domain, and the commons
Rai A, Boyle J. PLoS Biol. (2007)5(3):e58
PMID: 17355173
Article 2: Patents and Translational Research in Genomics
Kaye J, Hawkins N, and Taylor J. Nature Biotech (2007) 25(7): 739–741.doi: 10.1038/nbt0707-739.
Safety! Tue May 11? Article 1: Managing the unimaginable. Regulatory responses to the challenges posed by synthetic biology and synthetic genomics.
Samuel GN, Selgelid MJ, Kerridge I. EMBO reports (2009) 10(1):7-11.
DOI: 10.1038/embor.2008.232
Article 2: Darwin’s Surprise: Why are evolutionary biologists bringing back extinct deadly viruses?
Michael Specter New Yorker article
Programming Languages Tue May 11? Article 1: Towards programming languages for genetic engineering of living cells
Pedersen M, Phillips A J R Soc Interface 2009, 6(Suppl 4):S437-S450.
PMID: 19369220
Article 2: Cells Are Plausible Targets for High-Level Spatial Languages
Beal J, and Bachrach, J. Spatial Computing Workshop, October 2008.
Molecular and Cellular Computing Tue May 11? Article 1: An autonomous molecular computer for logical control of gene expression
Benenson Y, et al. Nature 2004 May 27;429(6990):423-9. Epub 2004 Apr 28.
PMID: 15116117
Article 2: Engineering bacteria to solve the Burnt Pancake Problem
Haynes KA, et al. J Biol Eng. 2008 May 20;2:8.
PMID: 18492232
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