FARM REPORT

Research Notebook

September/October 2012

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An image of a bacterium looking into a mirror. Reflected back is a computer simulating that same bacterium.
MODEL ORGANISM: M. genitalium was chosen for the first whole-cell computer simulation because of its small genome. (Image: Threestory Studio)

BIOTECH CAPTURES A BUG

A major accomplishment in computational biology by a team of researchers led by Stanford's Markus Covert gives new meaning to the term "computer bug."

With collaborators at Stanford and at the J. Craig Venter Institute, Covert, a bioengineering professor, and co-first authors Jonathan Karr and Jayodita Sanghvi, both graduate students, created the first computer model of an entire organism. Assimilating data from more than 900 scientific papers, their model accounts for every molecular interaction in the life cycle of the bacterium Mycoplasma genitalium.

A human pathogen that causes urinary and respiratory tract infections, M. genitalium was chosen because its genome, with only 525 genes, is among the smallest for a free-living organism. Even so, the simulated cell incorporates more than 1,900 behaviors observed in the living bacterium, modeling key biological processes—such as metabolism, protein synthesis, DNA replication and RNA transcription—as 28 interconnected modules.

The breakthrough was made possible by the rise over the past two decades of high-throughput technology capable of producing vast quantities of cellular data. The key, however, was "bringing all of that data into one place and seeing how it fits together," says Sanghvi.

Of course, "the goal hasn't only been to understand M. genitalium better," says Karr. "It's to understand biology generally." By allowing researchers to carry out procedures that would be difficult to perform in an actual organism, the model has the potential to do for biology what computer-aided design has done for engineering.

"Many of the issues we're interested in these days aren't single-gene problems," says Covert. "They're the complex result of hundreds or thousands of genes interacting. If you use a model to guide your experiments, you're going to discover things faster. We've shown that time and time again."

A map showing where music was played at Auschwitz. The voluntary areas and forced areas are roughly evenly distributed.
MEASURE OF CONTROL: Kagen mapped locations where "forced" (red) and "voluntary" (blue) music was played at Auschwitz. (Photo: Courtesy Benjamin Hein)

MANIPULATING MUSIC

As incongruous as it sounds, music played a significant role in the lives of prisoners in Nazi concentration camps. At Auschwitz, this included officially sanctioned concerts by the all-prisoner orchestra, command performances for SS officers, and subtly subversive songs written by prisoners to entertain their peers and resistance music that was hummed or whistled in secret.

In addition to the types of music played and sung—an eclectic mix of German marches, American jazz and ragtime, Jewish hymns and folk songs, and original tunes—what intrigued Melissa Kagen was where music was played within the prison. Mining survivor testimonies and camp administration records, Kagen, a doctoral candidate in German studies, created a set of interactive maps depicting what she calls the "musical geography" of Auschwitz.

Shaded in red are locations, such as the main gate, the railway siding and the courtyard outside the prisoners' kitchen, where "forced music" was played by the SS. Since sound traveled unimpeded through the thin walls of the barracks, "the melodies of Bach, Beethoven and Horst Wessel, along with jazz songs, wrested every last bit of space away from [the prisoners]," Kagen says. In these locations, she theorizes, the music served to help the guards—whose numbers were small relative to the prisoners—maintain control over large areas of the camp with minimal physical presence.

Still, the prisoners found the means to resist, using one of the only tools they had: their voices. Shaded in blue are locations such as the women's camp, changing rooms and personal effects depot where prisoners played, or in most cases sang, music of their own choosing. This so-called "voluntary music," Kagen hypothesizes, gave them a sense of autonomy and personal space, if only fleetingly.

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