Using a novel multiscale approach, researchers at the University of Illinois gain insight into a mechanism that suppresses gene expression.

An organism's genome contains all of the information required to build everything--all of the organs, cells, and cellular structures--the organism will ever need. The trick is building the right thing at the right time.

Visualization of the lac repressor protein (in blue) as it binds with DNA. The DNA is shown in yellow and red, with the protein-expression machinery shown as green spheres. By bending the DNA into a loop, the lac repressor prevents the expression of the proteins needed to metabolize lactose.

At any given time, DNA needs to be activated--to express a key protein, for example--or suppressed, holding back the potential to express that protein until it is needed.

Klaus Schulten, leader of the Theoretical and Computational Biophysics group at the University of Illinois at Urbana-Champaign, wanted to explore the mechanism that controls when a gene triggers expression of a protein and when that expression is held back. To tackle that question, his group used a novel multiscale approach that required both mathematical modeling and computational simulation using NCSA's Mercury Linux cluster, the largest computational resource of the National Science Foundation's TeraGrid cyberinfrastructure.

Lactose metabolism in E. coli

Schulten's group decided to examine a prototypical case of gene suppression in the bacterium E. coli.

When lactose is available in the environment, the bacterium needs to import and metabolize it. A set of genes, known as the lac operon, encodes the three proteins needed for this process. When environmental lactose is not available, the proteins are not needed, and the lac operon needs to be suppressed.

A protein known as lac repressor is responsible for holding these genes back. The lac repressor finds the lac operon segments of the genome, bending this stretch of DNA into a loop. This loop prevents expression of the lactose-metabolizing proteins.

Lactose is the key to this DNA lock. When the sugar becomes available in the bacterium's environment, it diffuses into the cell and unlocks the lac repressor. The loop is unleashed and the genes are expressed, resulting in the production of the three proteins that are necessary for lactose metabolism.

"This protein has an exemplary role in controlling genetic information," Schulten explains, which makes it an ideal candidate for research.

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