Structural genomics vs … the others

9 08 2007

There’s been some … communication … back and forth recently between those who support the Structural Genomics Initiative (i.e., received funding from the NIH for the protein structure initiative, or PSI), and those who, in so many words, think the PSI is a waste of resources.

For your reading pleasure:

a background article
Montelione GT. Structural genomics: an approach to the protein folding problem. Proc Natl Acad Sci U S A. (2001) 98(24):13488-9. [abstract/article]

an argument
Petsko GA. An idea whose time has gone. Genome Biol. (2007) 8(6):107. [abstract/article]

an indirect reply?
Liu J, Montelione GT, Rost B. Novel leverage of structural genomics. Nat Biotechnol. (2007) 25(8):849-851. [article]

I have to admit, I was excited to hear of the PSI when it was established in 2000, coincidentally the same year I began my graduate studies. Surely this would open up many research opportunities, in particular for structrual biologists!

Perhaps I was blinded by an intense blast of light, namely the “potential impact” hype, as I did not follow the PSI’s progress closely … that is, until I noticed this comment/article by Petsko.


Some scientists have argued that the PSI-1, which was funded between 2000-2005, produced structures of low-hanging fruit — structures that were easy to obtain, but did not significantly increase 3D structure/fold space. The PSI-2 (2005-2010) was a reformulation of the original PSI, designed to focus on more biologically relevant problems (taken from Petsko’s “article”):

  • to increase the number of sequence families with structural representatives, including families with high biological impact;
  • to continue methodology and technology development, especially for challenging classes of proteins such as membrane proteins;
  • and to facilitate the use of structures by the broad scientific community.
  • Petsko comments that

    “these goals are so squishy, it would almost be impossible not to meet them. Or for it to matter much if they were.”

    I think the blip of Petsko’s article sums it up quite well:

    “The $60 million a year in public money that is being spent on the Protein Structure Initiative is enough to fund approximately 100-200 individual investigator-initiated research grants.”

    It seems to me the PSI funding would be best appropriated to 100-200 individual scientists, rather than a handful of “PSI labs”. Why give funding for methodology and technology development to a small group of researchers, when there could be 100-200 individual labs working on solutions to hard structural biology problems?

    I wonder what the real biologists think about the PSI.




    One response

    14 08 2007

    I’m not the “real” biologist but I do think funding of PSI has much more sense than spending this money on 100-200 scientist. While the biological importance of PSI structures is often low, most of the difficult proteins are not even approached, we are systematically sampling the space of soluble and well defined proteins, which is also very important. The important biological stuff will get done anyway, with or without additional money.

    My impression is that the critics of PSI would criticize any large scale initiative – for example species sequencing – if that would be funded exclusively by NIH (Venter’s recent sequencing expedition was only partially funded by public money – from US Dep. of Energy).

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