I'm just curious, but after reading a number of Prof. Baker's recent journals I see a lot of good news regarding the progress that Rosetta is helping to make in regards to curing diseases.

The one question that is on probably everybody's lips is this: Just howclose are we to curing a major disease?

I know it still won't be for a while yet, but it'd be nice to hear, in a nutshell, how much of a contribution everybody on here has made.

Sorry if this post seems rather simplistic...I'm very, very tired!

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Alex it is a great question. I do not have the answer my self, but wanted to set up the framework for the answer you are likely to receive. You see much of the work Rosetta is doing is used to make a tool for the medical community to utilize and apply.

So, by asking how close to a specific cure we are, it is a lot like asking the company that makes metal detectors how close we are to finding a shipwreck. You see, it's not the maker of that tool that is going to go out and hunt for shipwrecks.

Having said that, the project involves many researchers at BakerLab and they've each got their individual focus on the development and use of this tool. After all, if you wanted to learn how to use a new metal detector, it might be useful to work directly with the manufacturer as you work to apply the tool to a specific task. And so some of the team is applying the tool to specific objectives, while others are working to make the tool better, and apply it to new areas (such as RNA).

Over the past year the complexity of the proteins being studied has increased exponentially, along with the addition of RNA and DOCKING tasks. There has also been research specific to AIDS conducted and Dr. Baker's Journal discusses the 15 vaccine candidates they have submitted as a result of that study.

My understanding is that the computed canidates are believed to mimic a portion of the surface of the AIDS virus, and the hope is that exposure to such a candidate will cause the body to develop immunity to the actual virus. So the first thing to do is to verify if the predicted behavior is correct. And this process starts by physically creating the sequence of amino acids of each of these candidates.

Then you can do chemical experiments to determine if in fact it behaves the way the models suggested. And then, if all goes well, you would begin to study wether in fact any immunity to the actual virus has been achieved. Since these are vaccine candidates, you would actually have to verify that the body's reaction to the vaccine creates an antibody that does in fact prevent an AIDS infection.

If it does in fact inhibit the virus, then you would need to determine if it has any adverse effects. My Dad tells me about how they used to spread powder on the garden to kill the bugs, it worked great! killed ALL the bugs... they didn't KNOW that it was harmful to humans as well! So, you can't just ASSUME that successfully inhibiting the virus means you've got the cure (and for a vaccine, "cure" wouldn't be the objective' "immunity" is the objective). If your vaccine also kills the patient, you've still got more work to do. So then you have to test for safety and effectiveness. Does it work for everyone? Or only certain individuals? etc.

...you can see it is a long, expensive process. And part of the reason they submitted 15 candidates rather then one is that some of them will certainly not function as hoped. But there is strength in numbers. If one is found not to work, try the next. The idea is to focus the rest of the research downstream on the best candidates very early in the process. As explained in Dr. Baker's journal, this is the first major project attempting to integrate the computer models in to the development process. So there is much to learn.

Thanks for your contribution to that effort.

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Rosetta Moderator: Mod.Sense

There used to be a popular history cable show called "Connections" by historian James Burke (I think). The theme of the show emphasized that each scientific breakthrough was built on previous work. At some point, bright people took this work and put parts of it together to make a significant discovery. As future advances in molecular biology and medicine appear, it would not be at all suprising to be able to trace the work back step by step and find Rosetta along the way.
Garry DeLong

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Both the questions and answers in this thread are excellent. The reality is that there are a number of steps to go from a designed protein to an actual therapeutic or vaccine used to treat people. The most time consuming and expensive step are clinical trials to see if the designed protein works as a desired as a drug or vaccine and to verify that it does not have any undesired effects. We are vey excited about the potential of the proteins we are designing to cure diseases, and believe that the approach we are collectively taking to developing cures are among the best possible, but it will take time to first, design a vaccine or therapeutic protein that has exactly the right set of biochemical properties, and second, to prove that the new protein acts as desired without side effects in people.

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Both the questions and answers in this thread are excellent. The reality is that there are a number of steps to go from a designed protein to an actual therapeutic or vaccine used to treat people. The most time consuming and expensive step are clinical trials to see if the designed protein works as a desired as a drug or vaccine and to verify that it does not have any undesired effects. We are vey excited about the potential of the proteins we are designing to cure diseases, and believe that the approach we are collectively taking to developing cures are among the best possible, but it will take time to first, design a vaccine or therapeutic protein that has exactly the right set of biochemical properties, and second, to prove that the new protein acts as desired without side effects in people.

So a good analogy might be to think of this like producing a diamond for a ring. What we're doing is the initial search through the ground for those rare uncut diamonds. By harnessing the power of a large collection of PC's it becomes possible to reduce this search to something manageable.

However even when we find something, a lot of work is still needed: this compares to cutting and polishing the gem before the ring is finally made. And not every uncut diamond can make a ring. Due to flaws in it, it may have to be cut into bagatelles that are used as highlights for something else.

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