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2009-11-27 11:50:26 | Weblog
[naturenews] from [nature.com]

[naturenews]
Published online 26 November 2009 | Nature | doi:10.1038/news.2009.1110
News
Single-celled life does a lot with very little
Bacterial biochemistry mapped in detail.

Lucas Laursen

The blueprint of a small organism's cellular machinery has been unveiled, offering the most comprehensive view yet of the molecular essentials of life. But the research also shows just how far biologists have to go before they understand the complete biochemical basis of even the simplest of creatures.

"Our whole attempt was to establish a model organism for systems biology," says Peer Bork, a bioinformaticist at the European Molecular Biology Laboratory in Heidelberg, Germany, and one of the coordinators of the project which surveyed Mycoplasma pneumoniae, a bacterium that causes respiratory infections.

The scientists catalogued the proteins produced in the cell, the RNA molecules transcribed from the DNA genetic code, and the chemical reactions which make up the cell's metabolism — also known as the proteome, the transcriptome and the metabolome.

{{“Our technology makes things possible that were unimaginable before.”}
Eva Yus
Centre for Genomic Regulation in Barcelona, Spain}

The researchers found that with its relatively short genome — it has just 689 protein-coding genes, compared with 20,000 or so in humans — M. pneumoniae presses some of its molecular machinery into multiple jobs. And the transcriptional activity of the organism seems to replicate that of larger, more sophisticated organisms.

The blueprint could help researchers to control or manipulate the bacteria that are already used to create desirable molecules, such as pharmaceutical compounds or enzymes that digest industrial waste. "The large amount of data focused on one organism is really valuable," says Erik van Nimwegen, a bioinformaticist at the University of Basel in Switzerland. The bacterium's metabolome, for example, should help biologists to model molecular activity in other cells.

"The results are a significant advance towards treating cells as the systems that they are," says molecular biologist Norman Pace of the University of Colorado in Boulder. The three studies are published today in Science1,2,3.

Old bug, new eyes

Although M. pneumonia is not the smallest organism on Earth, the researchers selected it because they had access to the lab protocols and notes that the retired German biologist Richard Herrmann had accumulated over the course of his career spent studying the bacterium.

The latest genetic sequencing technology meant that Bork and his collaborators could create a near-comprehensive description of the minimum molecular activity required to sustain M. pneumoniae. "Our technology makes things possible that were unimaginable before," says Eva Yus of the Centre for Genomic Regulation in Barcelona, Spain, the lead author on the metabolism paper3. "We can sequence a genome in a morning; a transcriptome in a few hours."

Their choice of a simple model organism sped up the genetic analysis and made the metabolic network analysis manageable. M. pneumoniae "has fewer than 200 enzymes", Yus notes, "so we could practically work out the reactions by hand".

Back to basics

Once Yus and her team had a metabolic map, they predicted the minimum nutrients necessary to grow the cells in vitro and tested 1,300 combinations of nutrients to learn how the organism responded to different environments. They eventually settled on a stripped-down medium with just 19 nutrients3, suggesting that the organism can use some enzymes for multiple tasks.

"One thing is clear," says Bork, "a single protein has several different jobs in a cell." This may help it to survive in many environments.

"This sounds plausible," says van Nimwegen. He adds that the result reinforces the idea that simplistic metabolic models, which assign just one function to each enzyme, "might be off by a lot".

Because the bacterium's genetic code did not seem to correlate with the complex protein activity observed using a mass spectrometer, the researchers are now looking for an intermediate regulatory pathway that adjusts protein behaviour.

van Nimwegen notes that the real fruits of such large, technology- and data-driven projects often take time to materialize. For now, the researchers "have set the example of how far you really have to go to more completely capture what is going on in an organism". But, he adds, there is still a long way to go before scientists can produce a complete molecular description of even the simplest cells.

References
1. Kühner, S. et al. Science 326, 1235-1240 (2009).
2. Güell, M. et al. Science 326, 1268-1271 (2009).
3. Yus, E. et al. Science 326, 1263-1268 (2009).


[naturenews]
Published online 26 November 2009 | Nature | doi:10.1038/news.2009.1109
News
Medical Research Council chief to step down
Early exit for Leszek Borysiewicz.

Geoff Brumfiel

{{Leszek Borysiewicz is leaving his post as head of the Medical Research Council to become vice-chancellor at the University of Cambridge.}
MRC}

Leszek Borysiewicz, the head of Britain's Medical Research Council (MRC), will step down in October 2010, a full year before his term expires. Borysiewicz, who has served as the MRC's chief executive since October 2007, is leaving to become vice-chancellor of the University of Cambridge, UK.
"It's a thrilling and exciting opportunity for me and one I feel I couldn't resist," says the 58-year-old.

The appointment has generally prompted acclaim for Borysiewicz from Britain's biomedical establishment. "Sir Leszek has been an outstanding leader at the MRC," Mark Walport, chief executive of the Wellcome Trust, Britain's largest biomedical research charity, said in a statement.

But for some, there is also anxiety over the future of the council. "I think that Borys has done an excellent job," says Colin Blakemore, a neuroscientist at the University of Oxford and Borysiewicz's predecessor at the MRC. But Blakemore says that he is "deeply worried about what this might mean for the MRC, especially for the support of basic biomedical research".

Borysiewicz has overseen a major increase in spending against a budget that reached £704.2 million (US$1.2 billion) this year. His scientific background, a mix of basic and applied bioscience, has been credited with helping the MRC to increase its emphasis on translational medicine, without losing its strength in basic research.

But the future seems less clear. Some researchers believe that the UK government's Department of Health may seek a larger stake in the MRC, pushing it further towards biomedical research and away from fundamental science. There are even worries that the MRC may be absorbed in the Department of Heath, or broken up.

With a general election looming next summer, Borysiewicz's departure "could make the MRC vulnerable at a very critical time", says Blakemore. "It will need a strong new leader, respected by both basic and clinical researchers."

But Borysiewicz says he sees little cause for concern. The council can claim 29 Nobel prizes, including one of this year's winners for chemistry, Venkatraman Ramakrishnan of the MRC Laboratory of Molecular Biology in Cambridge. Funding is healthy and relations with the rest of Britain's biomedical establishment are better than ever, Borysiewicz says. "The MRC is stronger now than it has been for a very long time."

Borysiewicz will officially leave his post at the MRC, and take up his new role at Cambridge, on 1 October 2010.

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