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Building the whole cell from pieces

Scientists have taken a significant leap forward in understanding the complex ways that molecules work together in cells. The work of the Structural & Computational Programme at EMBL-Heidelberg, in collaboration with Cellzome AG, appears in the current issue of the journal Science (March 26, 2004).

Although scientists already know a lot about single molecules, they know very little about how they are assembled into larger molecular complexes or "machines" and how these machines work together to create a complete, functioning cell. The problem is like trying to assemble a puzzle with billions of pieces with only the shapes of some pieces to go on.

"What we all aim for is a complete molecular anatomy of the cell to understand the big picture," says group leader Rob Russell, "That means finding out what machines are present in each part of the cell, what molecules make them up, and how they interact with each other."

One of the best ways to start a puzzle is to sort the pieces into sensible piles. That was extremely difficult until two years ago, when scientists from Cellzome and EMBL identified the components of hundreds of molecular machines in yeast cells.

"The information gave us more than a comprehensive list of the 'pieces' of protein machines it also suggested intriguing connections between them," comments Giulio Superti-Furga, Senior Vice President of Cellzome AG. "So the next step was to understand how they interact and work together."

Machines can be seen as fuzzy objects under the electron microscope, but the resolution isn't high enough to reveal how single components fit together inside the complex. Patrick Aloy, from Rob Russell's group, combined electron microscopy images (taken by the EMBL Group of Bettina Boettcher) with data from other experiments to find out how the shape and chemistry of single proteins allow them to fit together.

Computer methods developed by Aloy and Russell allowed them to fin
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Contact: Trista Dawson
dawson@embl.de
49-6221-387-452
European Molecular Biology Laboratory
25-Mar-2004


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