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Breakthrough in cell-type analysis offers new ways to study development and disease
Date:11/13/2008

Like skilled assassins, many diseases seem to know exactly what types of cells to attack. While decimating one cadre of cells, diseases will inexplicably spare a seemingly identical group of neighbors. What makes cells vulnerable or not depends largely on the kinds and amounts of proteins they produce - their "translational profile," in the lingo of molecular biology. For this reason, scientists have struggled to parse the subtle molecular differences among the hundreds of specialized cell types that are tangled together in tissues like the brain.

Now, in back-to-back papers in the November 14 issue of the journal Cell, researchers at The Rockefeller University report a breakthrough in cellular analysis that slashes through this Gordian knot. The scientists have developed a method to reveal translational profiles by isolating the genetic messages that govern protein production in different cell types. The new method, translating ribosome affinity purification (TRAP), uses genetically engineered mice to capture these messages as they pass through the protein production factories called ribosomes. Because the mice have been made to express a specially tagged ribosome in only one particular cell type, the TRAP method can identify all the genetic messages that give that cell type its unique identity, including, perhaps, its susceptibility to disease.

So TRAP solves a problem that has been a fundamental barrier to a deeper understanding of the brain and how neurological diseases attack it. But because the method can be used to distinguish any type of cell in any tissue in any organ -- not just brain cells -- it has applications for research into afflictions as varied as cancer metastases, coronary artery disease and diabetes. The work is a collaboration between the labs of Rockefeller professors Nathaniel Heintz and Paul Greengard as well as colleagues at Northwestern University and the Translational Genomics Research Institute (TGen).


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Contact: Brett Norman
bnorman@rockefeller.edu
212-327-7613
Rockefeller University
Source:Eurekalert

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