BioBrick standard biological parts are DNA sequences of defined structure and function; they share a common interface and are designed to be composed and incorporated into living cells such as E. coli to construct new biological systems. BioBrick parts represent an effort to introduce the engineering principles of abstraction and standardization into synthetic biology. The trademarked words BioBrick and BioBricks are correctly used as adjectives (not nouns) and refer to a specific "brand" of open source genetic parts as defined via an open technical standards setting process that is led by the BioBricks Foundation.
BioBrick parts were introduced by Tom Knight at MIT in 2003.[1][2] Drew Endy,[3] now at Stanford, and Christopher Voigt, at UCSF, are also heavily involved in the project. A registry of several thousand public domain BioBrick parts is maintained by Randy Rettberg team at http://partsregistry.org. The annual iGEM competition promotes the BioBrick parts concept by involving undergraduate and graduate students in the design of biological systems.
One of the goals of the BioBricks project is to provide a workable approach to nanotechnology employing biological organisms. Another, more long-term goal is to produce a synthetic living organism from standard parts that are completely understood.[4]
Each BioBrick part is a DNA sequence held in a circular plasmid; the "payload" of the BioBrick part is flanked by universal and precisely defined upstream and downstream sequences which are technically not considered part of the BioBrick part. These sequences contain six restriction sites for specific restriction enzymes (at least two of which are isocaudomers), which allows for the simple creation of larger BioBrick parts by chaining together smaller ones in any desired order. In the process of chaining parts together, the restriction sites between the two parts are removed, allowing the use of those restriction enzymes without breaking the new, larger BioBrick apart.[5] To facilitate this assembly process, the BioBrick part itself may not contain any of these restriction sites.[1]
There are three levels of BioBrick parts: "parts", "devices" and "systems".[3] "Parts" are the building blocks and encode basic biological functions (such as encoding a certain protein, or providing a promoter to let RNA polymerase bind and initiate transcription of downstream sequences); "devices" are collections of parts that implement some human-defined function (such as a riboregulator producing a fluorescent protein whenever the environment contains a certain chemical);[6] "systems" perform high-level tasks (such as oscillating between two colors at a predefined frequency).
Example BioBrick systems honored at previous iGEM competitions include:
- E. coli detector for arsenic that responds with pH change;
- E. coli producer of various scents such as banana or mint;
- human cell line engineered to inhibit excessive response to Toll-like receptor activation, so as to avoid sepsis.
The original BioBricks only use two of the compatible restriction enzymes XbaI and SpeI. Recently, Xu et al [8] have expanded this concept and used four of the compatible restriction enzymes AvrII, XbaI, SpeI and NheI. The engineered ePathBrick vectors comprise four compatible restriction enzyme sites allocated on strategic positions so that different regulatory control signals can be reused and manipulation of expression cassette can be streamlined. Specifically, these vectors allow for fine-tuning gene expression by integrating multiple transcriptional activation or repression signals into the operator region. At the same time, ePathBrick vectors support the modular assembly of multi-gene metabolic pathways and combinatorial generation of pathway diversities with three distinct configurations.
See also
References
- ^ a b Knight, T. (2003), Idempotent Vector Design for Standard Assembly of Biobricks. MIT Synthetic Biology Working Group.
- ^ Trafton, Anne (May/June 2011). "Rewiring Cells". Technology Review.
- ^ a b From the cells up, The Guardian, 10 March 2005
- ^ BioBricks to help reverse-engineer life, EETimes, 11 June 2004
- ^ BioBrick Formats
- ^ http://openwetware.org/wiki/IGEM:Caltech/2007/Project/Riboregulator
- ^ Part Types:Measurement Systems, Registry of Standard Biological Parts. Accessed 27 July 2008
- ^ Xu, Peng; Vansiri, Amerin; Bhan, Namita; Koffas, Mattheos A.G. (2012) ePathBrick: A synthetic biology platform for engineering metabolic pathways in E. coli. ACS Synthetic Biology,1 (7), pp 256–266.