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Synthetic Biology

Synthetic Biology is perhaps the hottest new topic to come from biology in the "post-genomic" era. Now that we know the code that goes into making life, we are trying to understand what it all does. One way to do this is to start from scratch and design our own string of nucleotides which will fold into a protein that has some function in the organism (the bacteria E. coli in most cases). By stringing known proteins together, we can start to design and build our own molecular machines with the help of biologists, engineers, physicists, computer scientists, and chemists.

A variety of engineered designs were created for and entered in the 2005 iGEM competion. These entries included chemotaxis regulation systems, cell-cell genetic communications systems, cellular/biological wires, thermometers, biological sketch pads (drawing systems), cellular relay races, a digital counter, and many more. At the core of these projects was the notion of a standard biological part that was well specified and able to be paired with other parts into subassemblies and whole systems.

Student-led research at Brown

The iGEM competition gives students the chance to spend 12 weeks on ground-breaking research in Synthetic Biology. Students will convene over the summer, spending their time designing novel engineered parts, modeling biochemical reactions, and then implementing these designs in the lab. A mentoring board will meet each week in order for students to report progress and to discuss new ideas. The project will contribute to advances in current research in Synthetic Biology. Previous entries in the iGEM competition have been published by students in the journal Nature [Voigt, 2005]. The competition provides a unique opportunity for Brown students engaged in the study of science to develop their own ideas and to start basic publishing valuable research.

Research Papers in Synthetic Biology

Timothy S. Gardner, Charles R. Cantor, and James J. Collins. 2000. Construction of a genetic toggle switch in Escherichia coli. Nature. Vol. 403. 339 - 342. (Bistable gene regulatory network, toggled by transient chemical or thermal induction, to serve as cellular memory)'

Vincent JJ Martin, Douglas J Pitera, Sydnor T Withers, Jack D Newman & Jay D Keasling. 2003. Engineering a mevalonate pathway in Escherichia coli for production of terpenoids. Nature Biotech. Vol. 21. No. 7 July 2003, 796 - 802.' "At Berkeley: Intelligently Designed Molecular Evolution". Research News Berkeley Lab. February 23, 2006.

Robert T. Batey, Sunny D. Gilbert, and Rebecca K. Montange. 2004. Structure of a Natural Guanine-responsive Riboswitch Complexed with a Metabolite Hypoxanthine. Nature. Vol. 432. 411 - 415. (Distinguishes Riboswitches from Aptamers and Antiswitches; also shows 3D structure of aptamer and ligand)

Laising Yen et al. 2004. Exogenous Controlof Mammalian Gene Expression through Modulation of RNA Self-cleavage. Nature. Vol. 431: 471 - 476. (mRNA-mediated regulation of translation)

Yina Kuang, Israel Biran, and David R. Walt. 2004. Simultaneously Monitoring Gene Expression Kinetics and Genetic Noise in Single Cells by Optical Well Arrays. Analytical Chemistry. Vol. 76: 6282 - 6286. (Analysis of two promoters)

Thomas Bulter, Sun-Gu Lee, Wilson WaiChun Wong, Eileen Fung, Michael R. Conner, and James C. Liao. 2004. Design of artificial cell-cell communication using gene and metabolic networks. PNAS. 101(8): 2299-2304. (Quorum sensor using acetate signal)

Hideki Kobayashi, Mads Kaern, Michihiro Araki, Kristy Chung, Timothy S. Gardner, Charles R. Cantor, and James J. Collins. Programmable cells: Interfacing natural and engineered gene networks. PNAS. 101(22): 8414-8419. (Toggle switch interfaced with 1) SOS signaling pathway for DNA damage response and 2) quorum sensing signalling pathway)

Sara Hooshangi, Stephan Thiberge, and Ron Weiss. 2005. Ultrasensitivity and noise propagation in a synthetic transcriptional cascade. PNAS. 102(10): 3581–3586. (Basic Research Paper)

Bayer, Travis S. and Christina D . Smolke. 2005. Programmable ligand-controlled riboregulators of eukaryotic gene expression. Nature Biotechnology. 23 (3): 337 - 343. (Antiswithces that turn off or on mRNA translation, regulated by amptamer binding ligands)

Isaacs, Farren J. and James J. Collins. 2005. Plug-and-play with RNA. Nature Biotechnology. 23 (3): 306 -307. (Commentary on Bayer & Smolke, 2005.)

Subhayu Basu, Yoram Gerchman, Cynthia H. Collins, Frances H. Arnold and Ron Weiss. 2005. A synthetic multicellular system for programmed pattern formation. Nature. Vol. 434:1130-1134 (Cool patterns, seeded with senders, with receivers responding to chemical gradients)

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