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WCG Status Update

WCG Post

HPF2 Taking the Long View: the merits of basic science
Hello crunchers,

In this status report I want to talk a little bit about the idea of basic research and where it fits into the priorities of science. Last year, there was a very high-profile HIV vaccine clinical trial that tragically failed. [article] This vaccine was anticipated to be very useful in preventing the transmissions of HIV but unfortunately vaccinated participants in the trial showed a higher rate of infections than participants who were not vaccinated. Not good. These are very expensive trials and raised a lot of hope in the public's eye. This setback in itself however wouldn't be a crisis to the field of HIV vaccine research but when scientists looked at the other prospective vaccines that were ready to be tested in clinical trials, they all were very similar to the one that failed and now many didn't show much optimism for success. The collective thought was "We put all our eggs in one basket". After realizing this, the NIH, (National Institute of Health, the major biological funding organization in the US) said there was a need to reprioritize and focus more on basic science and discovery research to come up with new ideas for vaccines. Its similar to the advice financial advisors give when they suggest you diversify your investments.

How does this relate to the Human Proteome Folding project and what lessons can we take from it?

All of the research done on the world community grid can be considered basic research. And all projects have a goal for the results to be used in a specific manner such as AIDS vaccines. Put another way, you aren't using your cpu cycles to do clinical trials on some drug that is under FDA review and will be on the market in 6 months. But every drug on the market today would not have been conceived without its beginnings in basic research. This is why this project and what you are a part of is so important to the future of biomedical research.

One big question in all this is "What basic research should we undertake in order to best cure the most awful diseases or looming human problems?" I'm sure many of you have already guessed the unfortunate answer is "We don't know. So how do we deal with all this uncertainty? Answer: We try really hard on a lot of different problems. But there is no reason why we should succeed. We might have the smartest, most dedicated people with the most probable solution to a problem and 9 out of 10 times it fails. What do we do then? We try ten different things. Essentially, we diversify.

You can diversity across many different aspects in science and one important and specific aspect the HPF project has diversified is the collection of organisms from which we try to fold. We're named Human Proteome Folding project for a reason because everything we're folding hopes to have direct impacts on human life (be it human drug targets, pathogen drug targets, understanding oceanic bacteria for applications in global warming, etc.) but what if none of that ever comes to fruition? What if all the human proteins are just much harder to fold than most other organisms (which they are ) and we fail at folding the human proteins? (These are just hypotheticals so don't get nervous. We're actually doing very well.) The thing that makes this all worthwhile if those things fail is we've diversified across all different types of organisms.

For an example of why this is important, let's say some researcher is not interested in specific clinical goals but rather is interested in some small metabolic pathway in some small bacteria that you and I have never heard of. They may discover what every protein does in their pathway and publish their results. Then some researcher working on a cancer pathway in human realizes that just one protein in her pathway overlaps with this protein from the small bacteria through structural homology (our database ) and the pieces begin to fall into place. It happens quite often.

Now this was a made up example but like we said before we don't know where the next big discoveries are going to come from and in folding proteins from over 80 genomes, we are building a huge resource for basic and clinical researchers all over the world.

So, here is our status on HPF2. Things have slowed down a little bit because of some new projects on the WCG and some other projects which were idle have started back up. At one point I think we were getting 40% of the grid, which we could barely keep up with. It was great. But we're still going at a pretty good clip. Thanks for all your hard work.

organism description status
plasmodium falciparum causes most deadly form of malaria (finished)
B. anthracis causative agent of anthrax (finished)
Gram-negative pathogens responsible for many food-borne illnesses and sexually transmitted diseases (finished)
Bacillus_subtilis model organism for studying evolution and other pathogenic organisms (finished)
GOS new antibiotics, new industrial enzymes, new organisms that bind toxic metals (finished)
plasmodium vivax recently sequenced genome which causes malaria, usually not deadly but truly awful disease (finished)
Phytoplankton responsible for a large portion of the oxygen in our atmosphere and interesting for its impacts on climate change (current, nearing end)
rice major food source for a large portion of the worlds population (not done)
arabidopsis model organism for studying plants (not done)
Trypanosoma cruzi causes Chagas disease in Central and South America (not done)




One final note to address a comment on the forums I just read. Someone was looking for the actual structures produced by the HPF project and as of now only the yeast structures are published. This is because folding proteins is a multi-step process and the computations done on the grid although by far the largest step isn't the only step. There is a post-processing step that gathers the results from the grid and calculates some probabilities and some other stuff. This takes a little while especially for the 125,000 or so proteins you've folded. But this is all done now for HPF1. We're currently doing some housekeeping chores like developing user friendly images (also a time consuming step and similar to the ones seen for yeast) for the web database and testing out the website. After that there are a few more steps for validation and verification before a paper is written and published. These last couple of steps aren't all that exciting (probably why we havn't mentioned them ) but are necessary for anyone to actually use these results. And given that HPF1 used over 26000 years of compute time, we want to spend the small extra amount of time to get it right. Thanks again for your patience.

Also, thanks to Sekerob the Community Advisor for addressing this on the forums. He does a great job keeping everyone informed.

Thanks,

Bonneau Lab

Further reading about the AIDS vaccine and basic science: http://www.nature.com/nature/journal/v452/n7187/full/452503a.html