Because death and disabilities from diabetes is significant and growing, perhaps mentioning it will help Rosetta. When Rosetta was started I got this nice reply when I asked about diabetes.

"Yes, there is a chance that this may eventually help with diabetes along with other serious, high profile medical issues and diseases. For example, there may already be researchers working on diabetes that are using our freely available structure prediction server, Robetta, which uses Rosetta and will hopefully be improved by this project. Or at least there may be in the future."

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Because death and disabilities from diabetes is significant and growing, perhaps mentioning it will help Rosetta. When Rosetta was started I got this nice reply when I asked about diabetes.

"Yes, there is a chance that this may eventually help with diabetes along with other serious, high profile medical issues and diseases. For example, there may already be researchers working on diabetes that are using our freely available structure prediction server, Robetta, which uses Rosetta and will hopefully be improved by this project. Or at least there may be in the future."

To the best of my knowledge, the most promising research in diabetes is related to various transplants, e.g. Pancreas, and Islet transplants, along with Beta / stem cell research. Alternative insulin delivery systems (e.g. pumps or nasal) are not really a correct solution to the problem, since they only serve to cure the symptoms, they do not cure the underlying problem in the way that a transplant does.

That being said, one of the major issues with a transplant is dealing with the rejection problem, in some ways you're trading one problem for another: anti rejection drugs can be very hard on the body.

There are then two possible areas that Rosetta could help with - firstly the rejection problem for transplant patients, but also, looking at that page on Beta cells, there may be an avenue that revolves around inhibiting the immune system's attack on the beta cells in the first place. This might only be able to help people who are susceptible to diabetes, although if it could be developed at sufficientlylow cost, it could become as commonplace as vaccines that are now routinely administered to all children.

So certainly, there may well be something that we can do. At this early stage though, we should turn our attention to refining the algorithm itself. The impression I get from David Baker's posts is that there is still much that needs to be done before we can use Rosetta for real research.

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Hi Ed&Harriet,

I think you are certainly correct that diabetes (especially Type II) is such a growing concern in North America, that including it in our research would certainly attract a lot of supporters. We did not include it in our "Disease Related Research" page because no one in Baker Lab is directly working on diabetes or diabetes proteins (such as insulin and its receptors) currently. We want to attract as many people as possible but we don't want to over-market what we are doing at the risk of giving a false impression.

Having said that, as the quote below from David Kim and the general paragraph in the Disease section indicate, a lot of what we are doing will benefit many diseases (anything involving a protein malfunction, which is almost everything).

Also, in the future we may recruit someone to work directly on diabetes related proteins. We are constantly recruiting new lab members, and they transform the direction of research in the lab with their own interests. In the meanwhile, as you know, our structure prediction and design program is freely available to academic users studying diabetes. Who knows, if Rosetta@home gets a high enough profile, it may attract collaborators working on any number of diseases, and that kind of synergy between an expert on, say, diabetes and our general protein design expertise could prove to be very powerful.

Cheers,
V.

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Edit: Why don't I read posts completely :)

But that is a big point. . any improvements to the Rosetta program itself can be (and is) used by many scientists around the world. Just because there isn't anyone in the lab doesn't mean there isn't someone outside the UW who would benefit.

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Great responses all! Because of the potential for eventually helping with diabetes, I suggest diabetes be listed under "Disease Related Research," on the front page.

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I will see what I can do to incorporate that suggestion. Thanks for a great suggestion and do keep them coming!

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I think Rosetta should turn its aim at diabetes too. more and more people are suffering from it. I have a chance of getting it; my grandmother died of it. My girlfriend and her father suffers from it too. and its also one of the reason why i am so interested in it.

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Victory is the ONLY option!

Hi Folks,

So I've been thinking a little more about diabetes and doing a little reading to find out what the molecular mechanisms of the disease are, since I didn't really know much about it. I learned a couple of interesting things that I thought you'd be interested in.

1)It turns out that protein fibrils are thought to be involved in type II diabetes, and since I know that one of the post-docs here is working on fibrils I asked him to write something to post here - and here is his reply:

"Under certain conditions, some proteins are able to transition from a folded, soluble state to a state in which many join together to form long, unbranching, insoluble ordered aggregates known as "fibrils". These fibrils can have two negative effects: first, they reduce the active population of this protein in the cell and second, the fibrils themselves are cytotoxic. Fibril formation has been implicated in several diseases, ranging from Alzheimer's to type II diabetes to Mad Cow disease. While each disease is related to the formation of these insoluble fibrils, symptoms differ due to the particular protein responsible for fibril formation in each case (as well as the parts of the body in which this protein is normally found) - a protein known as amyloid-beta forms fibrils in Alzheimer's disease, while fibrils in type II diabetes and Mad Cow disease are made of proteins known as islet amyloid polypeptide and prion protein, respectively.
Recent research in the Baker lab (in collaboration with David Eisenberg's lab at UCLA) has focussed on predicting the structure of fibrils formed by various parts of these proteins, as well as designing peptides which may prevent formation or propagation of these fibrils."

2) The second interesting thing I found out is that PPAR-gamma is involved in the etiology of type II diabetes, and is considered to be a promising drug target for the treatment of tIId. This was really interesting to me, as I am working on a related protein, called androgen receptor, which is involved in prostate cancer. While I need to focus my efforts on the AR because that is where my funding is coming from, I have certainly put PPAR-gamma on my list of interesting proteins to use in protein design. In the future, I may look more closely at how we can target PPAR with protein based drugs.

Cheers,
V.

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One of the things that drew me to FaD was the fact that it was targetting diabetes as well as a variety of other diseases. But finding universities that were interested in collaborating and validating the results has been problematic. The Rosetta client could run into the same problem - you need to find hospitals and universities that are interested in testing out and validating results from a DC project.

As I don't want to trade insulin injections for anti rejection drug(s) injections - I'll wait for either a cloned copy of my own pancreas complete with something to block the attack that killed off most/all of my islets of langehorn(sp) roughly 30 years ago. *grin*

Since that's not going to happen soon, I'm interested in helping out locating other strategies that will help. (And have taken part in a few DC projects that dealt with either basic research and applied research that was applicable to diabetes.) But we still need to break down the researcher's reluctance to use DC approaches..

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As the Father, Brother and Son of Type 1 diabetes sufferers all of whom are /were not overweight I hope Rosetta can be of help. As you can see it maybe that there is some genetic risk of the disease besides the dietary contribution.

I am in agreement with River~~ as far as HIV is concerned.

While we aren't directly involved in trying to develop therapies for diabetes (or MS) (we can't do everything well!), progress in predicting protein structures should contribute to the development of treatments. If we know the structures of proteins responsible for diabetes, for example, and whether their activity needs to be increased or decreased, we can search for small molecules that either activate or inhibit the protein.

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Hi folks,

Please continue to post here questions and suggestions on diabetes research and how Rosetta may (in future) help with the battle against this disease. I've moved the more philosophical discussion to this thread in the Cafe Rosetta message board.

Thanks,
V.

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Hi folks,

Please continue to post here questions and suggestions on diabetes research and how Rosetta may (in future) help with the battle against this disease. I've moved the more philosophical discussion to this thread in the Cafe Rosetta message board.

Thanks,
V.

Thanks Vanita - I accept the distinction you have drawn between the scientific and philosophical angles and your sifting of the previous messages is a good piece of moderation.

What I will say on this thread is that --despite our differences-- I am strongly in support of Ed's central point. Rosetta is developing a general purpose biochem tool, and we can reasonably expect that this tool will be of use in future diabetes research. That future potential can usefully included in the list possible long term benefits of this project.

Alongside Ed, I hope it will be.

I also hope that no attempt will be made in the disease related research pages to compare or contrast the alleged merits of one set of disease sufferers against others. Any such suggestion will alienate some potential donors of cpu time.

Comparison of the scientific angles, yes: how relevant (or not) Rosetta would be, prospects for a cure or for palliative treatment, all of that is OK. As far as I am concerned, all other comparisions should be excluded from the listings of disease related research.

I hope, despite our obvious differences, that Ed can unite with me in this.
River~~

One of the things I ran into over at FaD was that FaD has a collection of diabetes related structures that need to be tested out and seen if they're useable for diabetics. And by "useable" - I'm not referring to the tablet medication they had my father on - and the week after he switched to insulin and got his blood sugars back under control they pulled it off the market after 12? patients had died. There's supposed to be studies to properly test the safety of new meds; and it didn't seem to have been done thoroughly enough.

When Rosetta's client is used to locate new treatments or cures for diabetes, the project doing the locating will run into the same problem - finding diabetic research groups that are willing to test and/or fund the human use studies on what was found. I got no feedback from the diabetic research group I contacted; but if we track down enough of the diabetic research groups and get them interested in testing out results from diabetes related DC projects, then by the time Rosetta is being used on diabetes research we'll have wet labs ready to test the results.

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One of the things I ran into over at FaD was that FaD has a collection of diabetes related structures that need to be tested out and seen if they're useable for diabetics.

do you have a link for this? thanks to everyone's posts here, I am becoming more and more interested in learning about diabetes ...

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Based on the fact that we ran through a collection of diabetes related proteome queries; the only projects that were getting certificates for useable hits were Cancer and HIV; the fact that I never saw mention of a diabetes related collaborator (I wasn't corrected by Keith Davies when I stated that we needed one.) and I came to the conclusion that a collaborator for testing the diabetes results was still needed.

http://www.find-a-drug.org/forums/viewtopic.php?t=5660&highlight=diabetes
http://www.find-a-drug.org/forums/viewtopic.php?t=3358&highlight=diabetes
http://www.find-a-drug.org/forums/viewtopic.php?t=4887&highlight=diabetes
http://www.find-a-drug.org/forums/viewtopic.php?t=4390&highlight=diabetes
http://www.find-a-drug.org/forums/viewtopic.php?t=905&highlight=diabetes

Sorry.. falling asleep here. The first few touch on the topic, although the last is probably the best.

Vanita: visiting www.find-a-drug.org and clicking on the button to contact Keith directly might give an idea of how difficult it is to find diabetes collaborators for testing future diabetes results.

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Vanita,

How different is the androgen receptor protein in the male prostate different than a similiar protein in a female that has an estrogen receptor? I ask this because there are several well known treatments for post-menopausal women to prevent breast cancer (Tamoxifen, Arimidex, Aromasin) however I do not know of any medications treating older males that are at risk for developing prostate cancer?

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Senatoralex85 asked:

Vanita,

How different is the androgen receptor protein in the male prostate different than a similiar protein in a female that has an estrogen receptor? I ask this because there are several well known treatments for post-menopausal women to prevent breast cancer (Tamoxifen, Arimidex, Aromasin) however I do not know of any medications treating older males that are at risk for developing prostate cancer?

Ehhh, Senator? Vantia's post was done 5 months ago?...

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Join the Teddies@WCG

Ehhh, Senator? Vantia's post was done 5 months ago?...

Yes, I happen to come upon it searching the boards on an unrelated topic and that question popped into my head after reading that post. I saw vanita recently on the boards too. Anyone is more than welcome to answer the question.......

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Haven't been on the msg boards much lately, but saw your question today. Will answer properly when I have time this week.
Cheers,
V.

Vanita,

How different is the androgen receptor protein in the male prostate different than a similiar protein in a female that has an estrogen receptor? I ask this because there are several well known treatments for post-menopausal women to prevent breast cancer (Tamoxifen, Arimidex, Aromasin) however I do not know of any medications treating older males that are at risk for developing prostate cancer?

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Thanks Vanita!

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