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Cell growth regulates genetic circuits

Scientists from the Max Planck Institute of Colloids and Interfaces in Potsdam (Germany) and the University of California (United States) have shown how various genetic circuits in bacterial cells are influenced by growth conditions. According to their findings, even genes that are not regulated can display different activities; depending on whether they are translated into proteins in slow- or fast-growing cells. The results, published in 'Cell', provide researchers new insights into gene regulation and will help them in the design of synthetic genetic circuits.

A.R. | 1 February 2010

"Genetic circuits" consist of a network of different genes which can mutually stimulate or inhibit each other. With the help of these circuits, a cell can switch genes on or off and thus control what proteins it produces. However, genetic circuits also depend on the functioning of the cell as a whole to provide sufficient resources needed for building proteins. For example, Escherichia coli can adjust its generation time to anywhere between 20 minutes (under optimal conditions) and several hours (e.g. when food is scarce). The change in generation time or growth rate is accompanied by changes of almost all properties of the cells such as their size and their chemical composition.

By combining theoretical circuit models and experiments with simple synthetic circuits in bacteria the scientists demonstrated that growth rate decisively influences the activities of genes and thus genetic circuits. 

Changes within the cell affect protein concentration in various ways. For example, in faster-growing cells more RNA polymerases are available for the transcription of the gene, so the gene is read out more frequently. But there is also less time to accumulate the protein before the next cell division. In addition, faster-growing cells are bigger, so making the same number of protein molecules amounts to a smaller concentration. Assembling all that information in their model, the researchers were able to predict how the protein concentration would depend on the bacterial growth rate. What they discovered was that protein concentration decreases at faster growth rates - a result that matched well with experimental data for unregulated genes.

Researchers believe that these growth effects may be actively used in nature and could possibly even be beneficial for bacteria. When bacteria acquire new functions such as new metabolic abilities or tolerance to antibiotics, growth effects may regulate such functions without direct gene regulation. This could serve as a base from which a regulatory circuit may evolve later.
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