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The entire protein household of yeast: 257 machines that had never been observed

And now for another amazing example of what natural selection can accomplish (or not):

Press Release
Heidelberg, 22 January 2006
http://www.embl.org/aboutus/news/press/2006/press22jan06.html

The closest look ever at the cell’s machines: The first genome-wide screen for protein complexes is completed

“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 cellcycle 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 b ytechniques 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 the 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.

Source Article:
A.C. Gavin, P. Aloy, et al. Proteome survey reveals modularity of the yeast cell machinery. Nature, online publication 22 January 2006.

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23 Responses to The entire protein household of yeast: 257 machines that had never been observed

  1. Marvellous!!!

  2. A lilliputian wonderland of mind boggling machinery.

  3. Old programmers (such as myself) can see this as something like a “function library”:

    “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.”

    A function libray lets a programmer develop a system more quickly and more error free. For example, there might be a function for menu display: call the function with parameters and the same code displays different menu choices in different parts of the system.

    But here’s what’s interesting: functions are useless in and of themselves. Systems require functions and functions require systems.

    Now we see this sort of “reusable function” strategy happening at the cell level. Fabulous!

    It seems self-evident to me that “Certain features in nature appear to be best explained as the result of intelligence.”

  4. Perhaps Microsoft should hire the programmer creating these cells?

    Saxe

  5. Red

    DNA is a digital code composed of nucleic acid triplets (codons). A ribosome is a robotic pick & place machine that picks up amino acids and builds 3-dimensional components out of them. The ribosome does this following the encoded instructions found in DNA molecules. These components are then assembled into intricate machines including machines that duplicate the DNA molecule and the ribosome.

    This self-replicating program controlled factory complex is unprecedented in human experience or ability. Yet we understand enough of it to recognize that it is a vast machine of unparalled complexity.

    Nowhere in human experience has a machine of ANY complexity been encountered that was not the result of intelligent design. To deny all verifiable empirical evidence of how machines originate in nature to make an exception for the most complex machines ever observed is ludicrous.

    If this were ANY other field of science the notion that machines only originate through intelligent agency would be a law of nature instead of a subject for debate.

  6. Do I detect a faint hint of sarcasm in Professor Dembski’s opening line? :-)

  7. I suspect the press is dumbing down to the word “machine” from the word used among scientists, “enzyme”.

  8. Von Nuemann anyone?

  9. Off topic:

    Prof Dembski,

    What are you doing holding dice on a bridge??

    http://www.bbc.co.uk/sn/tvradi...../war.shtml

    Did any UK readers of this blog get to see it? (I couldn’t get to a TV unfortunately)

  10. I’ve said all along that ID would be vindicated by science. And I’ve taunted the PT bunch saying the same thing there. When will they throw in the towel?

    And, oh, by the way Xavier, there’s a difference between an ‘enzyme’ and a ‘machine’. An enzyme is (usually) nothing more than a ‘protein’, while the ‘machines’ they’re talking about are ensembles of proteins working in a coordinated fashion. There’s no “dummying down” here at all.

  11. antg

    “What are you doing holding dice on a bridge??”

    He appears to be illustrating the fact that bridges don’t get designed using random numbers.

  12. Xavier

    In your comment you’ve demonstrated that something is indeed dumbed down, but it isn’t the press, machines, or enzymes. Can you guess what it is?

  13. This is very cool. Its been my ( personal ) point of view to think of the designer as a computer programmer. Something I’ve wondered about was since most computer programmers leaves some kind of comments in (above / below) the code. Has something like this been found in the DNA or cellular level ? Sort of like:

    // its 2am im a bit sleepy but this genetic code creates the cell

    or some kind of genetic marker (or signature in a sense )that appears on all DNA ?

    Charlie

  14. Checking the source (the abstract at least. I don’t have an account with Nature, “cellular machinery” and “eukaryotic cellular machines” are used once each in the abstract. Would anyone else have access to the full paper? Perhaps the researchers are using “machine” in the French sense of apparatus, not necessarily with moving parts.

    A lot of wasted effort goes into strawman arguments, which could be avoided if people pay stricter attention to semantics.

  15. Charlie wrote:

    This is very cool. Its been my ( personal ) point of view to think of the designer as a computer programmer. Something I’ve wondered about was since most computer programmers leaves some kind of comments in (above / below) the code. Has something like this been found in the DNA or cellular level ? Sort of like:

    // its 2am im a bit sleepy but this genetic code creates the cell

    or some kind of genetic marker (or signature in a sense )that appears on all DNA ?

    As the human genome has been sequenced and published, there would seem an avenue for research here. Almost like SETI in miniature. Of course, not finding a signature would not disprove Intelligent Design, but if you did find such an unmistakable marker…

  16. DaveScot

    Intelligent Design IS a law of nature which is why it should never have been debated. Laws are not to be debated. They are to be accepted and diligently followed.

  17. Re Google Scholar of “cellular machinery”.

    I’ve no problem with that. It was the use of the unmodified “machine” that implies there is a newly discovered nano-machine in yeast cells, which I found misleading.

  18. Dr Davison

    That sounds rather ambitious. Do you have a working definition?

  19. Xavier wrote:
    “Has something like this been found in the DNA or cellular level? Sort of like:or some kind of genetic marker (or signature in a sense )that appears on all DNA?”
    ….
    This could be a fantastic plot for a science fiction novel.
    (BTW, quite a lot of scifi has come to pass–see Jules Verne, etc.)

    Background:
    In many computer programs programmers code in something called an “Easter Egg”.
    Windows 95 & 98 had one (Windows XP does not have one, it is said, because govt now requires all features to be documented).

    An “Easter Egg” can be anything, but usually, it is a display of the program’s “credits” and scrolls much like the credits that scroll at the end of a movie. Pictures, programmer’s names and responsibilities, all sorts of things will be displayed.

    But the “Eater Egg” can only be seen by following a complex set of steps that would NEVER be accidentally discovered. Someone has to tell you its there. For example in W98, you would “Open the Windows Date/Time Properties, click on the Time Zone tab (which reveals a time zone map), hold the CTRL key and left-click and hold on Egypt, drag mouse point to U.S. midwest, release mouse withOUT releasing the CTRL key, left-click again on U.S. midwest, drag mouse to Seattle, then release mouse and CTRL key. The “Easter Egg” will then begin.”

    OK. Here’s the scifi plot. Some scientists discover the “Easter Egg” coded in the Human Genome. HOW they find it could be part of the story. They actually MIGHT find it accidentally; that would be one way to do it, perhaps with the kind of technique used in the thread here. OR, there’ve been several books lately describing information that has been culled from the original Hebrew texts of the Old Testament by following patterns, for example, collecting every 128th character starting in Genesis and seeing what it says; so another way would be for a code say that was discovered 50 years earlier but meant nothing at the time, all of a sudden with the development of a new technique such as described in the thread above becomes meaningful. The scientists follow the procedure and Oujla! an “Easter Egg” coded into the DNA. Interesting subplot, Richard Dawkins and Eugenie Scott are on the team and this discovery blows their minds!!!! Word leaks out. Naysayers discount it say it doesn’t prove anything. Bloggers discuss it. Dave Scot boots some of them. Etc.!!! What a fun book. The whole theory of ID could be covered.

    O.K. If anybody runs with this idea, please put me down for the standard percent of a contributing royalty. THANKS.

  20. Red Reader

    That was Charlie, not me.

    In your comment you’ve demonstrated that something is indeed dumbed down, but it isn’t the press, machines, or enzymes. Can you guess what it is?

    DaveScot

    Attack ideas – not the people who hold them! :)

  21. Xavier

    Mea culpa. :-(

  22. Guess i watch too much scifi but that would make sense cuz im a scifi nut lol :)

    Charlie

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