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Intellectual Unit: Experimental Tools for Biological Discovery

Synthetic Biology: Cellular and Molecular Engineering

• link to idb website for this nanocourse

Instructors

• Nanocourse Lecturers: George Church (talk), William Shih (talk) (co-director), and Pamela Silver (talk) (co-director)

Course Description

Synthetic biology explores the design rules for building artificial behavior of biomolecular systems through cycles of construction and comparison of intended versus observed behaviors. The ability to synthesize biomimetic behavior is an important benchmark for biological understanding. This course will introduce strategies for engineering cellular and molecular systems and will explore current and future applications for synthetic biology approaches.

Meeting Times

• First Meeting: Monday, 2007 October 22nd, 1:30pm–4:30pm
  • Location: Goldenson 122 (on the HMS quad)

• Second Meeting: Friday, 2007 October 26th, 12pm–2pm
  • Location: Warren Alpert Building 436

Course Project

• The course project will be a 1-2 page proposal describing a synthetic biology project. Feel free to use figures in your proposal if it can clarify critical concepts for your readers. You should use the course lectures, course readings and your own experience to come up with a proposal. Your grade in this nanocourse will not be based on the validity of this proposal. Rather, we just ask that you make a best effort to propose a set of experiments to address an important problem. We will discuss these proposals during the discussion section of the course.
• All students should post their proposal, in Adobe PDF form, to this wiki page by noon on Thursday, 2007 October 25. (This is the day before the discussion section).
• Students and instructors should do their best to read each proposal before class on Friday. On Friday, 2007 October 26, each student will have a chance to informally present their proposed experiments to the entire class. Currently there are 8 students registered to participate on the second day, so we should be able to get through every student proposal.
• To see some potential project ideas, please browse through the project and brainstorming pages of former iGEM teams. If you decide to adopt one of those ideas, you should propose a significant improvement or alteration that represents value added to the original idea. Be sure to credit the sources for your inspirations. Here are some example links (everyone, please feel free to add more or to reorganize):
  • http://parts.mit.edu/wiki/index.php/Schools_Participating_in_iGEM_2006
  • http://openwetware.org/wiki/IGEM:Harvard/2007/Brainstorming
  • http://openwetware.org/wiki/IGEM:Harvard/2006/Brainstorming
  • http://openwetware.org/wiki/IGEM:MIT/2007
  • http://openwetware.org/wiki/IGEM:MIT/2006/System_brainstorming

Reading List

Lecture 1 (Silver)

• Recommended review articles

1. Drubin DA, Way JC, and Silver PA. Designing biological systems. Genes Dev 2007 Feb 1; 21(3) 242-54. doi:10.1101/gad.1507207 pmid:17289915. PubMed HubMed [pas1]
2. Voigt CA. Genetic parts to program bacteria. Curr Opin Biotechnol 2006 Oct; 17(5) 548-57. doi:10.1016/j.copbio.2006.09.001 pmid:16978856. PubMed HubMed [pas2]
3. Andrianantoandro E, Basu S, Karig DK, and Weiss R. Synthetic biology: new engineering rules for an emerging discipline. Mol Syst Biol 2006; 2 2006.0028. doi:10.1038/msb4100073 pmid:16738572. PubMed HubMed [pas3]

• Additional papers of interest in the field

4. Chang MC and Keasling JD. Production of isoprenoid pharmaceuticals by engineered microbes. Nat Chem Biol 2006 Dec; 2(12) 674-81. doi:10.1038/nchembio836 pmid:17108985. PubMed HubMed [pas4]
5. Anderson JC, Clarke EJ, Arkin AP, and Voigt CA. Environmentally controlled invasion of cancer cells by engineered bacteria. J Mol Biol 2006 Jan 27; 355(4) 619-27. doi:10.1016/j.jmb.2005.10.076 pmid:16330045. PubMed HubMed [pas5]
6. Deans TL, Cantor CR, and Collins JJ. A tunable genetic switch based on RNAi and repressor proteins for regulating gene expression in mammalian cells. Cell 2007 Jul 27; 130(2) 363-72. doi:10.1016/j.cell.2007.05.045 pmid:17662949. PubMed HubMed [pas6]
7. Ajo-Franklin CM, Drubin DA, Eskin JA, Gee EP, Landgraf D, Phillips I, and Silver PA. Rational design of memory in eukaryotic cells. Genes Dev 2007 Sep 15; 21(18) 2271-6. doi:10.1101/gad.1586107 pmid:17875664. PubMed HubMed [pas7]
8. Basu S, Gerchman Y, Collins CH, Arnold FH, and Weiss R. A synthetic multicellular system for programmed pattern formation. Nature 2005 Apr 28; 434(7037) 1130-4. doi:10.1038/nature03461 pmid:15858574. PubMed HubMed [pas8]
9. Elowitz MB and Leibler S. A synthetic oscillatory network of transcriptional regulators. Nature 2000 Jan 20; 403(6767) 335-8. doi:10.1038/35002125 pmid:10659856. PubMed HubMed [pas9]

Lecture 2 (Shih)

• Recommended review articles

10. Yeh BJ and Lim WA. Synthetic biology: lessons from the history of synthetic organic chemistry. Nat Chem Biol 2007 Sep; 3(9) 521-5. doi:10.1038/nchembio0907-521 pmid:17710092. PubMed HubMed [wms1]
11. Alvizo O, Allen BD, and Mayo SL. Computational protein design promises to revolutionize protein engineering. Biotechniques 2007 Jan; 42(1) 31, 33, 35 passim. pmid:17269482. PubMed HubMed [wms2]
12. Breaker RR. Natural and engineered nucleic acids as tools to explore biology. Nature 2004 Dec 16; 432(7019) 838-45. doi:10.1038/nature03195 pmid:15602549. PubMed HubMed [wms3]
13. Seeman NC. DNA in a material world. Nature 2003 Jan 23; 421(6921) 427-31. doi:10.1038/nature01406 pmid:12540916. PubMed HubMed [wms4]

• Additional papers of interest in the field

14. Kuhlman B, Dantas G, Ireton GC, Varani G, Stoddard BL, and Baker D. Design of a novel globular protein fold with atomic-level accuracy. Science 2003 Nov 21; 302(5649) 1364-8. doi:10.1126/science.1089427 pmid:14631033. PubMed HubMed [wms5]
15. Dwyer MA, Looger LL, and Hellinga HW. Computational design of a biologically active enzyme. Science 2004 Jun 25; 304(5679) 1967-71. doi:10.1126/science.1098432 pmid:15218149. PubMed HubMed [wms6]
16. Rothemund PW. Folding DNA to create nanoscale shapes and patterns. Nature 2006 Mar 16; 440(7082) 297-302. doi:10.1038/nature04586 pmid:16541064. PubMed HubMed [wms7]
17. Douglas SM, Chou JJ, and Shih WM. DNA-nanotube-induced alignment of membrane proteins for NMR structure determination. Proc Natl Acad Sci U S A 2007 Apr 17; 104(16) 6644-8. doi:10.1073/pnas.0700930104 pmid:17404217. PubMed HubMed [wms8]

Lecture 3 (Church)

• Recommended review articles

18. Forster AC and Church GM. Synthetic biology projects in vitro. Genome Res 2007 Jan; 17(1) 1-6. doi:10.1101/gr.5776007 pmid:17151344. PubMed HubMed [gmc1]
19. 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, and Endy D. DNA synthesis and biological security. Nat Biotechnol 2007 Jun; 25(6) 627-9. doi:10.1038/nbt0607-627 pmid:17557094. PubMed HubMed [gmc2]

• Additional papers of interest in the field

20. Lartigue C, Glass JI, Alperovich N, Pieper R, Parmar PP, Hutchison CA 3rd, Smith HO, and Venter JC. Genome transplantation in bacteria: changing one species to another. Science 2007 Aug 3; 317(5838) 632-8. doi:10.1126/science.1144622 pmid:17600181. PubMed HubMed [gmc3]
21. Herring CD, Raghunathan A, Honisch C, Patel T, Applebee MK, Joyce AR, Albert TJ, Blattner FR, van den Boom D, Cantor CR, and Palsson BØ. Comparative genome sequencing of Escherichia coli allows observation of bacterial evolution on a laboratory timescale. Nat Genet 2006 Dec; 38(12) 1406-12. doi:10.1038/ng1906 pmid:17086184. PubMed HubMed [gmc4]

Uploaded Proposals

Remember to upload a PDF of your file by Thursday, October 25th by noon. Uploading your file on time means that your fellow classmates and instructors will have ample time to carefully read all of the proposals. Please name your files something meaningful. I suggest the following format... NameofStudent_syntheticbiology2007.