A Conversation for Prions

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Post 1

Orcus

Hi Mugwump if I may be so familiar. smiley - smiley

Just read through your article on Prions and it is very good.
Not really much to add but did you know that the lastest research I have seen on protein folding seems to indicate that all protiens are potential 'prions'. I saw a lecture, can't remember who gave it I'm afraid, where the lecturer described his current work on this. Basically, prions aggregate by a beta-sheet - beta-sheet interraction and it is quite well known amongst those who synthesise new peptides that purification of peptides that form beta-sheet structures is exceptionally tricky as they always tend to aggregate, hence most work has concentrated on alpha-helix structures. He tought he'd take a look at this and found conditions where he could fold any protein he chose into predominantly beta-sheet configurations and they would form into huge aggregates. The aggregates took the form of huge helix structures and were exceptionally stable to protease degradation, heat, uv etc. Sounds like a prion huh?
This doesn't yet have any bearing on vCJD or anything but might have very large significance on our attempts to live to 200-300 years old. Essentially the theory is that as cells get older, various organelles within age and stop working properly, proteins begin to misfold, aggregate etc. Alzheimers, Huntingdon's Chorea and other diseases may work this way.
Anyway, nice article, just though you might be interested in this.


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Post 2

Salamander the Mugwump

Thanks for that Orcus. It's all fascinating stuff. I've come across information suggesting that the alpha-helical PrPc changes, probably, to a predominantly beta-sheet conformation in prion diseases. The tendency of the beta-sheet form to aggregate is new to me but it fits in neatly with the story so far. Also, from what I've read upto now, it wouldn't surprise me if, as you say, it was found that all proteins could potentially 'flip'.

The whole prion thing is really cutting edge. I'm sure there'll be lots of surprises in store.

Sal smiley - smiley


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Post 3

Orcus

It certainly is, and as I said to Wumbeevil (for twas he who pointed me in your direction) its nice to see people on h2g2 writing science on subjects other than black holes, superstring theory and other aspects of theoretical physics.
Keep up the good work.

Orcus &


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Post 4

Salamander the Mugwump

Good old Wumbeevil! Have you read his pieces on Eukaryotic Cell Structures, The Mitochondrion and The Golgi Apparatus? It's a biggish project. He's going to link them. It'll be pretty comprehensive when he's finished.

And have you seen Ariel's entry on Hearing the World Around Us? I think he's currently working on an entry on hearing in bats. I can't wait to read it.

I've done 3 entries now and they've all been about things that I found fascinating but knew very little about. It gave me an excuse to roll up my sleeves and get stuck in to researching something that I thought lots of other people would find interesting too. I thought it would be a worth-while challenge to take something fairly technical and render it into plain English so that anyone could understand it.

Not sure what to do next. I've been toying with the idea of doing an article on animals with blue blood or perhaps just focusing on one animal that's especially interesting in its own right - the horseshoe crab - making its blood a central theme. Can you think of anything deeply fascinating that the folks should be told about?

Sal smiley - smiley


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Post 5

Orcus

Hmmm, the horseshoe crab, actually an arachnid if my memory serves me correctly. Actually, it was from reading, and commenting on Wumbeevils article on eukaryotic cell structure that I found you. Not seen Ariel's entry but I'll have a look. I'm extremely impressed on the article about Prions if you knew very little to start off with smiley - wow, I was maybe thinking of doing some stuff related to my own work, but now you mention it, it would be more interesting to write about something other than shop.
I'm not really the best person to ask on ideas for the guide, I register about 18 months ago and have only gotten off my arse to do one article so far and that was last week.

*Racks brain* - Eek, where's it gone! smiley - yikes

Bacterial drug resistance - a hot topic at the mo, interesting in so much as how it happened and of course what we're going to do about it in the future. Easy for me, it was my PhD topic.
E. Coli - might be an idea to set the reord straight as everyone thinks its an evil bacteria now - when we always have around a kilo of it on average in our intestines.
Maybe have a look at how they're trying to increase our lifespan.
The human genome project (or has that already been done?)
The sex life of Sloths.
Antifreeze creatures (ie. fish etc in the antarctic that have antifreeze proteins in their blood).
Archaebacteria.

Dunno if anyone's interested in these but me though. smiley - erm


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Post 6

Salamander the Mugwump

Gosh, 18 months - you're a real old timer! smiley - winkeye 'Bout time you started telling us all the things you think we might like to know. I agree with you about the science subjects. I'm quite interested in the physics stuff but some of it's a bit difficult to follow and a lot of it seems very speculative. I prefer things I can understand - where I don't have to wonder whether the impediment to my understanding is the difficulty of the subject matter, the way it's written or my stupidity. A few solid facts are always nice too. smiley - smiley

I think the horseshoe crab is very very distantly related to arachnids - certainly closer to spiders than insects. Spiders have blue blood too, I believe. That's the fun of it. I don't really know much about them yet so I'm going to have to do a lot of research before I can do the article.

All the subjects you mentioned would be great for entries. There's a little tiny bit about drug resistance and e. coli in my bacteriophage article. Not much more than a brief paragraph. If your PhD is about bacterial drug resistance you've done all the work so it would be a shame not to do an article for The Guide. There's an article on animals that freeze solid, by Pseudmys. I left him a message on it ages ago about tardigrades (he didn't reply though). An entry on animals that don't freeze would sort of complete the set. It would be good to see an entry on archaebacteria too. I get the impression they've been a bit misunderstood - not very closely related to bacteria, as initially thought. Sex life of sloths? They don't look as though they might be interested, do they? The human genome project and increasing our lifespans ... You've got enough great ideas to keep you busy for ages. I think they'll go down a storm at peer review. Really interesting stuff!

Sal smiley - smiley


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Post 7

Orcus

Just saw your comment on my St. Andrews article. Thankyou very much, and no bribing required smiley - winkeye. Have a wee smiley - donut anyway for the compliment.

Actually, I've probably only really been on h2g2 about three or four months in total. I only had work access to the internet before and they cracked down on web surfing at work last January so I had an enforced lunch break as it were. Back with a vengence now.

The arachnid thing came from drunken argument I had with someone down the pub. smiley - bigeyes He was insisting that crabs and lobsters were arachnids and 'he knew because he was a biologist'. Thinking 'er they're crustacea aren't they?' I looked it up on the web. The first hit I got on arachnids gave the horseshoe crab as one of them. This of course is far from reliable, I look forward to something far more reliable and informative from your very self. smiley - smiley

You certainly are encouraging. Actually, I'm begining to get bored just playing around on the chat forums and not doing anything else and I actually enjoyed teaching myself the GuideML for the St Andrews article - and there's so much more to learn. Drug resistance it is then... Watch this space.

BTW, I saw this nature program once where they mentioned that nobody had ever seen sloths mating. Just a thought really smiley - winkeye


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Post 8

Orcus

Hello again, just read your article on Bacteriophages. Again, excellent and in fact I didn't know some of that stuff. They do indeed sound like a very good solution to the drug resistance problem. Two things, there is also a type of phage called a lambda phage although I don't actually know if this is included already in T1-T7. Also, did you know that they are very widely used in science in genetic engineering. Basically, you copy stretches of DNA encoding the protein (or proteins) you wish to make and then stitch it into a phage's DNA (they often use the lambda phage for this). The phage is then known as the 'vector' and you infect E. coli with it. The phage is not of the lethal variety but will stick your DNA into the bacterium's genome. Your transformed bacterium will then merrily make the protein you require, in this way you can get bacteria to make human, monkey, or cucumber proteins.

If/when I ever get to writing my Drug resistance article, it should probably be linked in some way with yours as it will probably be quite complimentary.

BTW. I've added you to the 'Nice people I have met on H2G2' on my home page for your nice compliments on my St Andrews article. Hope you don'y mind.


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Post 9

Salamander the Mugwump

Your St Andrews article is good and I would've read it and said so earlier if I'd known there might be a doughnut in it for me smiley - winkeye

Right then. Horseshoe crabs it is. Now I know I'm not the only person who wants to know more about them. Once I've finished messing about with my tax return smiley - groan I'll get cracking.

And I look forward to reading your entry on drug resistance. I like the idea of a link to my bacteriophages. I think all you have to do is put a note on your article to tell the editor that you want a link. I put in a link to the DNA article but for some reason the sub-ed removed it. Perhaps he would've left it alone if I'd also put in a note. Anyway, glad you like the article.

I came across a little bit on the lambda phage. It didn't say that it was one of the T1-7s, just that it was one of the temperate phages that infect e. coli and that it quite often cut loose from its host rather carelessly, taking some of the host's DNA with it. It makes sense that if the lambda has a habit of making off with extra DNA, it would be a natural for use in genetic engineering. It's very interesting. I'd have liked to put more about genetic engineering in the article but it went into editing before I could find any more data. It almost didn't get it's penultimate paragraph on testing bacteria for drug resistance. I had to pester the sub-ed and assistant ed to get it included.

Thank you very much for adding me to your nice people list. I'm deeply honoured!

Sal smiley - smiley


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