Continuing the battle against Ebola
As you know, the current Ebola outbreak in Western Africa has now claimed over 1,000 lives, making it the worst Ebola outbreak to date. Currently, no proven treatment or vaccine exists to combat Ebola. It has been some time since our last Ebola design puzzles (http://fold.it/portal/node/997612 and https://fold.it/portal/node/997525) were posted. These, in combination with the initial hotspot-finding puzzle (https://fold.it/portal/node/996919), have both yielded some great leads that we are currently working to test in the wet lab. In particular, some of the best player hotspots yielded excellent starting points for the design of small, cyclic peptides that we're quite excited about.
The process of going from a candidate design to a drug ready for deployment in the field is a long one. We start by screening a large number of candidates for binding to the Ebola surface glycoprotein, using high-throughput methods. Because the Ebola virus is obviously quite dangerous, we can't work with it ourselves in our wet lab. We therefore use Ebola proteins that have been made in harmless strains of bacteria, using recombinant DNA technology. As for the candidate designs, we express these in baker's yeast, also using recombinant techniques. Because we are using high-throughput methods at this stage, we expect some false positives from our screen. Some candidates, for example, are just generally "sticky", and bind to pretty much anything. These would not be useful as drugs, since they'd stick to all sorts of other things in the body, but they show up in the initial screen as a hit.
Once we have some possible hits from our initial screen, we express and purify larger amounts of these second-round candidates for more careful experimental validation using lower-throughput techniques. At this stage, we need to do careful controls to confirm that the second-round candidates aren't just generally sticky. We also start to get quantitative at this point, to see whether a design binds tightly enough to be a useful drug, or whether it needs further redesign to improve its binding affinity.
Through collaborators, we will ultimately test candidates that pass all of our tests in cell culture, then in animals infected with the virus. The road to human trials is longer still, since it's necessary to show that a drug is safe before it can be given to sick people. Even with a disease as horrible as Ebola, one has to be sure that the treatment isn't worse than the disease. We're not yet anywhere near the stage at which candidates could be administered to people suffering from the Ebola virus -- but with time, effort, and patience, we hope to get there.
In the mean time, now that CASP is winding down, we will be posting a few more Ebola puzzles in the next few days. In particular, I'm curious about whether players could do better than the automated algorithms at designing a heavily disulfide cross-linked peptide to bind to the Ebola glycoprotein... We look forward to finding out!( Posted by v_mulligan 130 2255 | Thu, 08/14/2014 - 04:32 | 0 comments )
Save the Date: Devchat August 19
Happy Monday, folders!
We are genuinely pleased to announce the return of regularly scheduled developer and science chats. For the rest of 2014, we have currently scheduled chats for the following dates:
August 19 1400-1500 Pacific (or convert to your time zone here).
December 2 (to get one more in before the holidays)
While we will likely be adding others to our roster as needed (in the event of exciting collaborations and the like), you should definitely get your questions ready for August 19 and post them in the comment thread to this post. We'll be starting our chat with questions on this thread before opening up the floor for more, so make them count!(Mon, 08/11/2014 - 16:38 | 22 comments)
The recent devprev release had some scoring issues on certain puzzles that were not intended. We have reverted the devprev client to be identical to the current main while we sort out the issue.
If you are running the old devprev client, your scores will not be reported (a message should pop up telling you this). You'll need to restart and get the reverted client before you can get credit again.
Thanks!(Sat, 08/09/2014 - 15:34 | 3 comments)
Final week of CASP11!
The final contact-assisted targets of CASP11 are expected to be released on Monday, and the last Foldit puzzles for CASP11 will close by August 17. Over the next week or so, we will transition back to a more relaxed and diverse puzzle load. We're anxious to see more player-designed proteins, and have some new ideas for Ebola virus and Alzheimer's disease research.
But for now, there are 8 active CASP11 puzzles, and several more in the queue! Stay with us and help us finish the CASP11 season strong! We've been very impressed with Foldit player participation this year, and are excited to see how our players compare with protein structure-prediction labs from around the world. Analysis of CASP11 submissions will extend for several weeks after the targets expire, and we will keep you informed of results from the CASP11 organizers (or from our own lab) as they become available.
Keep up the great CASPing!(Sat, 08/09/2014 - 02:19 | 2 comments)