Wednesday, May 09, 2007

Old Fart Teaches Young Whippersnappers a Lesson with Phages

Its no secret that I have a certain level of... 'disdain'... for my academic/research 'superiors' when they put themselves in a position to be corrected by students/laymen/me. *cough* *cough* *cough*

There is another side to that coin-- sometimes people teach me things that are so revolutionary, so mind-blowing, that I instantly develop maddening mind crushes on them, and I obsess over their research for months. Todays I found a new object of obsession: Michael Rossmann.

I never thought Id say this about a structure guy, but, Oh. My. God. SOOOOO AWESOME! His brain! SO AWESEOME!!!

Quick summary of his ideas--
Here is a T4 bacteriophage. Not symmetrical. Got that big head on one end, some whiskers, some gangly legs--- weird little mo-fo. Its cellular host is a prokaryote.

Then look at a virus that infects a eukaryote, like, a rotavirus. Nice symmetrical icosahedron... Right?

Lets look at something nice and big, like a Mimivirus. It infects archaea (not a eukaryote), but if you take a look at that Wiki cartoon, it looks like the rotavirus. Nice symmetrical icosahedron. No whiskers. No syringe tail. Just a bouncy ball! Whats cool about Mimi, is that unlike most viruses which need to be specially treated and measured with a crazy microscope to be visualized, we can just stain Mimi and look at it under a regular microscope!

In the left frame, you see the nice symmetrical bouncy ball. Zoom in... zoom in... WHATS UP WITH THAT VERTEX ON THE BOTTOM IN THE RIGHT PIC??? WHAT IS THAT?

Thats a unique vertex, thats what that bastard is.

So heres what has happened-- Over the past couple decades as weve been taking pictures of viruses. All these pics of viruses we have? They have to be taken with a special microscope that averages all the pictures it takes into a composite image. If one vertex of the icosahedron is 'different', when you average that one in 60 (60 vertices), the 'different' vertex disappears. Assymetry turns into symmetry.

DOH!

ARG! ALWAYS remember your assumptions when you are doing an experiment! Making averages makes sense, technically (taking pics without averaging is 60 times more work), but if you forget your assumptions (we did) and forget phages (we did), you arent seeing what you think youre seeing!!!

The implication of icosahedral viruses having a 'special' vertex explains so much, and turns up a billion more questions!

With phages, one virus means one infected cell. Its that easy. Eukarotic viruses are much less efficient-- I can cover a plate of cells with HIV, and not every cell gets infected. Maybe cause there is only one vertex that actually attaches to the cell surface and HIV doesnt have legs like a T4!

And what does this mean for the evolution of viruses? Certainly viruses arent monophyletic, but did the phage tail come first? Did eukaryotic viruses have a tail at one point, but lost it as eukaryotes evolved (a tailed virus wouldnt last 5 second with our immune system)? Or did everyone start out as a bouncy ball (the 'easiest' structure) and phages got tails after eukaryotes broke away from the Net of Life?

SOOO COOOOOL!!!! SO MANY IMPLICATIONS!!! AHHHHH!!!



Thanks to Stanford for the Mimi pic!

3 comments:

Wanderin' Weeta said...

Wow!

I am reminded of a bit of ancient history; back in the early 1960s, my microbiology prof showed us a fuzzy photo, taken with the new-fangled electron microscope, of -- Ta-daa! -- a virus! Just a grey, fuzzy spot, but it gave me the shivers, just to think we could actually see these critters.

Time has passed; I had to leave University for health reasons, and now I watch from the sidelines.

And your post, with the odd-ball vertex on a virus, seen and photographed, the doorway to a whole new area of exploration, gave me those same shivers again.

Awesome!

Dr. Duke said...

I suspect you are overinterpreting this. I doubt that all phages and viruses share a single common ancestor or that phage "tails" have evolved or devolved just once.

Remember, only a few phages look like T4. M13 is completely different. I am not sure we even know what most phages look like.

And not at eukaryotic viruses are alike either, some are enveloped and some are not. Some infect fungi, some infect plants.

ERV said...

Weeta-- I know what you mean! During Rossmanns presentation by heart was pounding, I was sitting on the edge of my seat... AH so coooool!

Duke-- Oh yeah, no way do all viruses have a LUCA. And not all phages have tails or the same kind of tail and such (Had to keep the post kinda brief!) But the web, how everything could have evolved-- that looks different to me now after seeing Rossmanns pics! I forgot all the examples he had looked at thus far-- I can only remember canine parvo-- but they had a special vertex. I dont think theyve looked at enough viruses to say "Oops- all the icosahedral viruses have a special vertex" yet. I still think the fact that some of them do is revolutionary :)