Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The closest look ever at the cell’s machines

23.01.2006


The first genome-wide screen for protein complexes is completed



Today researchers in Germany announce they have finished the first complete analysis of the ”molecular machines” in one of biology’s most important model organisms: S. cerevisiae (baker’s yeast). The study from the biotechnology company Cellzome, in collaboration with the European Molecular Biology Laboratory (EMBL), appears in this week’s online edition of Nature.

“To carry out their tasks, most proteins work in dynamic complexes that may contain dozens of molecules,” says Giulio Superti-Furga, who launched the large-scale project at Cellzome four years ago. “If you think of the cell as a factory floor, up to now, we’ve known some of the components of a fraction of the machines. That has seriously limited what we know about how cells work. This study gives us a nearly complete parts list of all the machines, and it goes beyond that to tell us how they populate the cell and partition tasks among themselves.”


The study combined a method of extracting complete protein complexes from cells (tandem affinity purification, developed in 2001 by Bertrand Séraphin at EMBL), mass spectrometry and bioinformatics to investigate the entire protein household of yeast, turning up 257 machines that had never been observed. It also revealed new components of nearly every complex already known.

In the course of the work, new computational techniques were developed at EMBL that gave new insights into the dynamic nature of protein complexes. In contrast to most man-made factories, cells continually dismantle and reassemble their machines at different stages of the cell cycle and in response to environmental challenges, such as infections.

“This would be a logistical nightmare if the cell had to build every machine from scratch any time it needed to do something,” says Anne-Claude Gavin, former Director of Molecular and Cell Biology at Cellzome and currently a team leader at EMBL. “We’ve discovered that the reality is different. Cells use a mixed strategy of prefabricating core elements of machines and then synthesizing additional, snap-on molecules that give each machine a precise function. That provides an economic way to diversify biological processes and also to control them.”

Thus if the cell needs to respond quickly, such as in a disease or another emergency, it may only need to produce few parts to switch on or tune the machine. On the other hand, if something shouldn’t happen, it may only need to block the production of a few molecules.

Patrick Aloy and Rob Russell at EMBL used sophisticated computer techniques to reveal the modular organisation of these cellular machines. “This is the most complete set of protein complexes available and probably the set with the highest quality,” Aloy says. “Most proteomics studies in the past have shown whether molecules interact or not, in a ‘yes/no’ way. The completeness of this data lets us see how likely any particular molecule is to bind to another. By combining such measurements for all the proteins in the cell, we discovered new complexes and revealed their modular nature.”

“Investigating protein complexes has always posed a tricky problem – they’re too small to be studied by microscopes, and generally too large to be studied by techniques like X-ray crystallography,” says Russell. “But they play such a crucial role in the cell that we need to fill in this gap. There’s still a huge amount to be learned from this data and from the methods we are developing to combine computational and biochemical investigations of the cell.”

“This is an important milestone towards a more global and systems-wide understanding of the cells of organisms ranging from yeast to humans,” says Peer Bork, Head of the Structural and Computational Biology Unit at EMBL, and one of the authors of the paper. “Ultimately we hope to achieve a ‘molecular anatomy’ that takes us from the level of the entire cell to the much deeper level of all the molecules and atoms that make it up.”

Baker’s yeast is evolutionary related to the cells of animals and humans, which means that the findings will be more widely applicable. “The same principles discovered here in yeast apply to human cells,” says Gitte Neubauer, Vice President at Cellzome. “Drug targets and pathologically relevant proteins are parts of machines and pathways.”

The collaboration between Cellzome and EMBL has been very successful, she says, producing fundamental new insights in how molecules are organised and contributing to Cellzome’s success in complex and pathway analysis.

Anna-Lynn Wegener | alfa
Further information:
http://www.embl.org/downloads/press06/press22jan06.html

More articles from Life Sciences:

nachricht Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz

nachricht Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>