Q&A: The protein bias

At the dawn of the 21^st century, scientists completed the first draft of the human genome and reported that human cells encode more than 20,000 proteins. But most of the protein research performed since has focused on about 2,000 proteins (mostly enzymes) that were already known and whose functions were well studied, according to an analysis published this week in Nature.

Image: Wikimedia commons

The Scientist spoke with lead author linkurl:Aled Edwards;http://www.utoronto.ca/AlEdwardsLab/al_edwards_bio.html about this apparent research bias. Edwards, a biochemist at the University of Toronto and director of SGC, a nonprofit that encourages research on proteins of medical relevance, describes why scientists appear to be stuck in their old ways and what can be done to encourage exploration into the unknown.The Scientist: What led you and your colleagues to recognize this research bias?Aled Edwards: It was really driven by a sense by our pharmaceutical partners that it wasn't worth the effort in studying the kinases anymore. And we thought that was quite ridiculous because there were lots of [kinases], and they had barely been tapped.So we searched the literature of the last 60 years for mentions of each member of three families of human proteins that are known to be relevant for drug discovery -- kinases, ion channels and nuclear receptors -- and what we found was, unfortunately, it doesn't look like we're moving beyond the myopic area that we've been working on. We're working on a small set of proteins, and usually the set of proteins we were working on a decade or two decades ago.TS: Why is it important to work on a wider array of proteins?AE: Clearly, they exist for a reason. And as time goes on, more and more and more of them have genetic links to disease. So ultimately one's pretty sure it's going to be all of them.TS: Why do you think researchers are less likely to study previously unexplored systems?AE: The first [reason] is that scientists are sometimes just like dogs with a bone: They just love their problems. And they love going deeper and deeper, and it's the richness and the complexity of their problem that drives them. The other thing is that you can get funding for proteins for which there's a preexisting community. The third thing is that when you rationalize your grant, we get rewarded for the elegance for which we weave a tale. You need to have context. When you go to publish a paper, if you work on an unknown protein, you're less likely to capture the imagination of the peer reviewers and they'll probably ask for a lot more work. To study an unknown protein, it takes longer, and that's what nobody has in this modern world -- time.And then the last thing is research tools. There is no molecular biologist now who would not prefer to use a genome wide knockdown set of RNAis, for example, as opposed to the single RNAi. That's a better experiment, but no such tools exist for proteins. If you have a new protein, you have to make a knockout cell, you have to make an antibody, an inhibitor or mutant. It's a lot of work to create the infrastructure to even do the experiment. TS: What can be done to overcome these obstacles?AE: We've heard ideas from friends that maybe the peer review community should set up committees especially for the purpose of rewarding those who go into the unknown. Universities can acknowledge that a scientist who spends his or her time going into the unknown is less likely to publish in the one word journals. But those are institutional systems that we argue are probably less likely to be able to change quickly then by enabling scientists with research tools. I think the data [are clear]: When the researchers are provided with the tools, they will do those experiments. It's a fairly objective and innocuous way for permitting work into the unknown. TS: What would be the motivation for somebody to make a tool for a protein that hasn't yet been studied closely?AE: There is no commercial value, and it's very hard to justify because we usually justify scientific projects based on the importance of the protein we're targeting. So it's certainly a circular argument. I think this has got to be targeted research, [where] money is targeted for a specific purpose. It's difficult to do it because there's a large body of the scientific community that does not believe that that kind of science is worth doing when there are so many fantastic projects that aren't being funded. So it's a real tension in the system. Great science is not getting funded at the same time as most of the genome is lying fallow. A. Edwards, et al., "Too many roads not taken," Nature, 470: 163-5, 2011.
**__Related stories:__***linkurl:Two-faced proteins?;http://www.the-scientist.com/news/display/57916/
[11th January 2011]*linkurl:mRNA affects protein fate;http://www.the-scientist.com/blog/display/57692/
[17th September 2010]*linkurl:Related F1000 evaluations;http://f1000.com/search/evaluations?query=protein+research
[9th February, 2011]