Field of Science

Multicellular signalling

ResearchBlogging.orgI like studying bacteria. I find them fascinating, wonderful little creatures, able to do as much (and often more!) with a single cell as other organisms need whole multicellular bodies to achieve. I like exploring the places bacteria live, the things they can do, the ways they manage to exploit practically every niche on earth, and of course most importantly how I can exploit them.

But not everyone loves bacteria, and at heart I am a biochemist which means, among other things, that I get to teach younger biochemists. This means I do occasionally find myself venturing uncertainly into the world of the multicellular and while doing so recently I found an interesting paper on cell signalling (reference below) which I thought I would share.

All cells need to be able to communicate, but while bacteria know that everyone they communicate with is a competitor, multicellular organisms have cells that need to be able to cooperate in a strange and slightly twisted form of cellular-communism. Each cell needs to know when it can divide (usualy never), when to grow, when to release chemicals and, ultimatly,when to sacrifice itself for the Greater Good.

Cellular communication is mostly a chemical affair, with small molecules called ligands being sent from one cell to another and recognised by receptors on the cell surface. These receptors can take many forms, but one of the more common ones is the form of a seven-transmembrane spanning receptor, so called because it goes through the membrane seven times:

Picture (c)me and my dodgy art skills. The protein is in blue, the membrane in pink, and the ligand bound on the outer cell surface is the red blob.

Binding of a ligand causes a conformational change in the whole structure, most importantly in that long intracellular tail shown above. This can then activate other molecules inside the cell, with the end result that a specific gene is turned on or off. In the classical model of this process the intracellular tail interacted with a little molecule called the G protein which carried the message through to the genome. Another protein that featured in this model was B-arrestin, which was thought to desensitise the receptor and the G-protein by re-setting it back to its original state, i.e switching the thing off. This model is shown below:

Picture (c) me. This is a simplified diagram, in 'reality' there are a lot more different proteins involved, but these are the main ones, and the important ones for this paper.

New evidence is coming to light which modifies this model. Firstly, it's been found that the B-arrestin does more than just switch off the G-protein, it is also capible of sending its own signals, through a cascade of different proteins. Both the G protein and the B-arrestin can be used to pass on the message sent by the ligand. Secondly, it's been found that these two proteins are not activated equally, a bias can be displayed, sending the signal through one of these two intermediate proteins; either the G protein, or the B-agonist or a mixture of the two. This bias can be either due to the properties of the receptor, or those of the ligand binding to it. Experimentally you can generate a bias by altering either the receptor or the ligand to prefer binding to the B-agonist, and you can plot these on mathematical-looking graphs.

You can tell this is a biology graph because there are no actual numbers, just vague concepts :p (c) me.

The actual physiological effects of this are only starting to be explored, as it introduces an extra level of complexity to intracellular control. The use of several different ligands, all with varying degrees of bias at the same receptor, could produce more subtle cellular output responses. Within a multicellular organism, the better your intracellular communication is, the more likely your organism is to grow happily and survive.

Rajagopal S, Rajagopal K, & Lefkowitz RJ (2010). Teaching old receptors new tricks: biasing seven-transmembrane receptors. Nature reviews. Drug discovery, 9 (5), 373-86 PMID: 20431569
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Designers know how to party...

Last Tuesday was the Brit Design Award of the Year Nominees party. It took place in the Design Museum in London, which was full of wonderful displays showing off cars, computer games, small models of architectural wonders and some random coloured bacteria...

The E. chromi display table for the Brit Design of the Year Award

The display table showing off the E. chromi project (i.e coloured bacteria) was almost exclusively organised by Daisy and James, our two awesome designers. One side covered the work we did during iGEM, with resin moulds made to look like bacterial streaks for each colour, next to very diluted DNA preps for each sample (homeopathic DNA by the time I'd diluted it enough to be acceptable for display purposes :p ).

The DNA sequence is written above the test-tube. It was hard to take this picture without a reflection of the camera showing. Also there were people behind me who wanted to actually see the display and I didn't want to block them for too long.

The other side of the table was the colour-futures side, which featured various potential applications of our work. Pride of place was for the Scatalog, the wonderful idea of using coloured bacteria to sense any internal infections or illnesses by swallowing bacteria in a Yakult-style yoghurt drink and producing a clear colour signal in, well, in poo. We also had a prototype kanamycin bomb, used by future protesters against colour patenting to wipe out the bacteria responsible for specific colour production.

Orange Liberation Front - free the rainbow!

The most amazing thing about this, more amazing than being nominated for anything, was that people were seeing our work. That's something that I'm learning doesn't happen all that much in science. Unless it's published, work barely gets out the lab, and even then unless you're very lucky it seems to stay within the field you're working in. To suddenly see a large number of random people looking at our work was a fascinating experience. Not all of them totally understood it, and the fake-poo in the scatalog certainly got some very odd looks but it was getting out there. In public.

I love designers. They make my science awesome :D

Coloured bacteria vs. Angry birds

For those who didn't catch the news when it first came out, the iGEM project I carried out in the summer of '09 has been nominated for a Design Award! The Brit Insurance Design of the Year 2011 to be precise.

I'm very excited about it, even though I don't really feel like a designer (I don't own a singlething made by Apple). We're up against some pretty intense competition, such as the Angry Birds phone game, Rock band 3 and quite a few phone apps. Still, it's pretty awesome to be nominated, and I'm looking forward to seeing all the rest of the project displays.

Our two wonderful designer-friends James King and Daisy Ginsberg have put together a great video explaining the project. It's got some great animation, and clips from a radio interview with one of my fellow lab rats, and even some pictures of the infamous Orange Liberation Front...

E. chromi from Alexandra Daisy Ginsberg on Vimeo.