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Brewing a Better Killer

8 August 2005 (All day)
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Sinking feeling. As the number of DNA repeats in FLO1 decreases, yeast clump together less, and the solution becomes cloudier.

Sticky, infectious yeasts cause more deaths than any other hospital-acquired germ, and researchers now have an inkling as to why. The number of repeating sequences within the organisms' DNA can vary dramatically from cell to cell, resulting in changes to the cells' surface that confuse drugs and the immune system. Because these changes can also affect how yeast cells stick together, the findings may help explain why some beers are clear and others cloudy.

Scientists have known about DNA repeats for over 50 years, but the function of these elements has remained unclear. Some have been implicated in human disorders, such as Huntington's disease and fragile X syndrome. But because they tend to stick around generation after generation, geneticist Kevin Verstrepen--who led the new study in the lab of geneticist Gerald Fink at the Massachusetts Institute of Technology in Cambridge--wondered if the repeats also play a positive role.

Verstrepen and colleagues looked at brewing yeast, a popular genetic model. The team found that 44 of the yeast's genes had repeats, 60 percent of which were responsible for cell surface proteins. The number of repeating units was found to vary among the yeast cells, potentially changing the protein makeup of the cell surface. Since medications often target specific features of these surfaces, this adaptation may allow the yeasts to disguise themselves while evading the immune system, Verstrepen says.

One of the genes, called FLO1, is known to play a role in cell adhesion, so the researchers decided to test the adhesive properties of yeast with different numbers of repeats in their FLO1, gene. They found that yeast with more repeats in FLO1, stuck to plastic plates better than those with fewer repeats did. Yeast with more repeats in FLO1, also clumped together more strongly and sank more rapidly to the bottom of test tubes, the researchers report online 7 August in Nature Genetics.

The differences may explain why some beers are cloudier than others, Fink says. The more yeast clump, the more they sink, and the clearer the beer, he explains. Verstrepen adds that scientists may be able to genetically engineer specific numbers of repeating units in yeast to create beers with a desired clarity.

"This is a very exciting finding," says James Haber, a geneticist at Brandeis University in Waltham, Massachusetts. "It's a very nice demonstration of a functional consequence of repeating sequences." Tom Petes, a geneticist at Duke University in Durham, North Carolina, adds that it would be interesting to find out how these findings in yeast apply to human proteins, and if these changes are random or if there are environmental factors that influence them.

Related sites
Fink's home page
Verstrepen's home page

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