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A logical approach to designer cells
18 December 2007
Logic gates made from proteins could lead the way to yeast cells that can self regulate during fermentation, say US scientists.
A team led by Virginia Cornish at Columbia University, New York, has designed a transcription factor that functions as an AND logic gate. Transcription factors are proteins that form part of the system controlling the transfer (transcription) of genetic information from DNA to RNA. It usually possesses a DNA binding domain and an activation domain. When both domains are turned on, transcription occurs. This gate forms part of an artificial transcription factor network for programming functions in a cell. Cornish explained that the networks are designed 'like electrical circuits with transcription factors functioning as Boolean logic gates.'
All three components of the transcription system are needed to switch transcription on
Using a well-defined yeast system, the US researchers genetically separated the DNA-binding domain and the activation domain so that transcription only occurs in the presence of a small molecule ligand (Dex-Mtx). On one end of the small molecule ligand is dexamethasone (Dex) which has high affinity for the activation domain whilst at the other end of the ligand is methotrexate (Mtx) which binds to the DNA-binding domain. Dex and Mtx are held together by a carbon linker. In this system, the DNA-binding domain, the activation domain and the ligand (Dex-Mtx) form the three inputs of the logic gate. When all the three inputs are turned on, the output is transcription. This is analogous to a three-input AND gate.
Nicholas Buchler, an expert in the field at Rockefeller University, New York, US, said that this will 'greatly benefit' research into engineering cells capable of making small molecules. Jonathan Bronson, who works with Cornish, suggested the technology could be used to 'create yeast cells that could monitor conditions in a fermentor and adjust themselves to optimise ethanol/glycerol production.'
Ron Weiss, a specialist in cell programming using logic circuitry at Princeton University, US, said that he hopes that this 'system can be adapted to different proteins inside the cells, creating multiple versions of AND logic gates.'
Bronson plans to go one step further and obtain 'a toolkit of transcription factors capable of performing many types of logic gates, like NAND, that could be used to create any genetic circuit that we can imagine inside a microbe.'
Link to journal article
Transcription factor logic using chemical complementation
Jonathan E. Bronson, William W. Mazur and Virginia W. Cornish, Mol. BioSyst., 2008, 4, 56
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