>>>
The idea behind the project is to make mosquitos resistant to the parasite by eliminating genes required in the mosquito for the parasite to live.
<<<

Why can't you research making the mosquitoes catch malaria and die. That way, we are spared malaria AND mossie bites!

HIV: One of the reasons that HIV is such a deadly virus is that it has evolved to trick the immune system. We are collaborating with researchers in Seattle and at the NIH to try to develop a vaccine for HIV. Our role in this project is central--we are using rosetta to design small proteins that display the small number of critical regions of the HIV coat protein in a way that the immune system can easily recognize and generate antibodies to. Our goal is to create small stable protein vaccines that can be made very cheaply and shipped all over the world.

HIV: One of the reasons that HIV is such a deadly virus is that it has evolved to trick the immune system. We are collaborating with researchers in Seattle and at the NIH to try to develop a vaccine for HIV. Our role in this project is central--we are using rosetta to design small proteins that display the small number of critical regions of the HIV coat protein in a way that the immune system can easily recognize and generate antibodies to. Our goal is to create small stable protein vaccines that can be made very cheaply and shipped all over the world.

David,

I've been pondering about this explanation of your plans for working on combatting HIV, and was wondering how accurate the following "layman's explanation" is. The reason I'm curious is that I want a 15 second sales pitch that I can use to do a real hard sell for Rosetta.

Would the following be one way of describing what you have in mind.

The big problem with HIV is that your immune system can't see it, and so doesn't do anything about it. What Rosetta will do is help design a big bucket of red paint that we can splash on the virus. This says "HEY GUYS, OVER HERE!" to your immune system, so that it can see the virus and go to work on it.

HIV: One of the reasons that HIV is such a deadly virus is that it has evolved to trick the immune system. We are collaborating with researchers in Seattle and at the NIH to try to develop a vaccine for HIV. Our role in this project is central--we are using rosetta to design small proteins that display the small number of critical regions of the HIV coat protein in a way that the immune system can easily recognize and generate antibodies to. Our goal is to create small stable protein vaccines that can be made very cheaply and shipped all over the world.

David,

I've been pondering about this explanation of your plans for working on combatting HIV, and was wondering how accurate the following "layman's explanation" is. The reason I'm curious is that I want a 15 second sales pitch that I can use to do a real hard sell for Rosetta.

Would the following be one way of describing what you have in mind.

The big problem with HIV is that your immune system can't see it, and so doesn't do anything about it. What Rosetta will do is help design a big bucket of red paint that we can splash on the virus. This says "HEY GUYS, OVER HERE!" to your immune system, so that it can see the virus and go to work on it.

Sorry about missing this--there are too many things to follow on the message boards these days (we need help!).

You are close. the outer surface of HIV is extremely variable, so when an infected person has an immune response to it, the antibodies don't do anything because the virus has already changed. but there are a few key "Achilles heel" regions where the virus can't change because it needs these regions to keep infecting people, get into cells, etc. Unfortunately, the immune system doesn't usually make antibodies to these regions, because the variable parts are much more noticeable to the immune system (this is one of the ways in which the virus is very tricky). Our idea is to take these "Achilles heel"
regions that are critical to the virus, and embed them into small stable proteins which could be sent all over the world very cheaply. The hope is that when vaccinated with these proteins, people will make antibodies to these Achilles heel regions (because in contrast to when on the real virus, on the vaccine they will be very conspicuous). So then people will have antibodies which can "neutralize" the virus (indeed, several "neutralizaing" antibodies have been found in patients, and they do recognize the Achilles heel regions, but they are normally either not made or made at very low levels).

You are close. the outer surface of HIV is extremely variable, so when an infected person has an immune response to it, the antibodies don't do anything because the virus has already changed. but there are a few key "Achilles heel" regions where the virus can't change because it needs these regions to keep infecting people, get into cells, etc. Unfortunately, the immune system doesn't usually make antibodies to these regions, because the variable parts are much more noticeable to the immune system (this is one of the ways in which the virus is very tricky). Our idea is to take these "Achilles heel"
regions that are critical to the virus, and embed them into small stable proteins which could be sent all over the world very cheaply. The hope is that when vaccinated with these proteins, people will make antibodies to these Achilles heel regions (because in contrast to when on the real virus, on the vaccine they will be very conspicuous). So then people will have antibodies which can "neutralize" the virus (indeed, several "neutralizaing" antibodies have been found in patients, and they do recognize the Achilles heel regions, but they are normally either not made or made at very low levels).

...If the body doesn't readily and frequently recognize these portions of the virus outer surface as portions that would instigate an auto-immune response, then what good would vaccinating someone against these proteins do?

Even if the body had been vaccinated, the antibodies wouldn't be released in force unless the body recognized a potential threat. - Which.. if it recognized HIV in this way, it would create the proper antibodies anyway. Or do I have the wrong impression of the immune system?

Or maybe I am just thinking too hard :)

...If the body doesn't readily and frequently recognize these portions of the virus outer surface as portions that would instigate an auto-immune response, then what good would vaccinating someone against these proteins do?

Even if the body had been vaccinated, the antibodies wouldn't be released in force unless the body recognized a potential threat. - Which.. if it recognized HIV in this way, it would create the proper antibodies anyway. Or do I have the wrong impression of the immune system?

Or maybe I am just thinking too hard :)

As I understand it (as a physicist, not a bio) the point is that the HIV virus offers a number of obvious targets to the immune system, but they are disposable decoys rather than the really vital unchangeable targets.

By putting the real targets up _without_ the cunning distractors, the immun system has a better chance of getting it right. Then when the real HIV arrives, the unchangeable targets are visible enough for the immune system to attack.

It attacks what it knows even tho they are a little less visible than the decoys

Am I in the right ballpark here?

My research group is involved both in fundamental methods development research and in trying to fight disease more directly. Most of the information on this site focuses on basic research, but I thought you might be interested in hearing about some of the disease related work we are doing.

Malaria: ...

Anthrax: ...

HIV: ...

...

With the wonderful contributions all of you are making, we can now make much more rapid progress on the disease fighting front. ...

Thanks again for all your help, and happy thanksgiving!

David

[b]"I'm trying to maintain a shred of dignity in this world." - Me[/b]

I feel so excited and proud of being able to participate in this, all thanks to BOINC and the guys over at Seti with their visions and foresight!

But how does one get this structure from a virus?

And in getting this structure, how is one not able to see the commonalities between samples?

But to me it's just like a photographer taking pictures of an actor. No matter what the actor dresses in, the photographer can eventually notice that in each picture ... there's a mole that doesn't cover up.