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Novel method to reveal drug targets
Date:2/22/2008

from these proteins simply because there was no efficient method to examine them. Effectively, a swathe of clinically important targets is invisible to research.

"AVEXIS now allows us to scale the hunt for biologically and clinically important protein-protein interactions," continues Dr Wright. "These interactions are like Velcro - each hook can bind only weakly, but together, they can have a very strong effect. We increased the strength by gathering the proteins together, as in a small scrap of Velcro."

The team identified previously undescribed interactions in a class of proteins called the immunoglobulin superfamily: this group of proteins shares properties that are important to allow cells to respond to their environment, talk to one another and stick together. Using human proteins and zebrafish as a model, the Sanger Institute researchers looked at interactions between 110 proteins in this superfamily - a total of more than 6000 experiments.

They found 17 interactions that met stringent standards of reliability, several of which would last for less than 0.1 seconds in cells. For each, they looked to see where the proteins were located in zebrafish embryos. They found, broadly, two categories; those in which both protein partners are present in the same tissue (and likely to be involved in cell adhesion) and those in which they are present in adjoining tissues (and therefore likely to be involved in communication between tissues). Half of the proteins interact with more than one other protein, forming interaction networks.

The results provide the first network of low-affinity interactions between proteins on the cell surface and the first set of extensive data in the zebrafish, a leading organism for following visually the effects of gene disruption.

"AVEXIS is not restricted to only one specific organism and could be used in many contexts," explains Dr Wright. "We found in the zebrafish novel interactions for well-s
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Contact: Don Powell
don@sanger.ac.uk
44-012-234-96928
Wellcome Trust Sanger Institute
Source:Eurekalert

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