Over the Christmas period I have been trying out a few beers, including Brewdog’s weirdly named Self Assembly Pope. This beer is a porter, with some cocoa, coconut and vanilla added to spice it up. It is a pretty good porter, although I am not a big fan of coconut, on its own or in beer, and so probably will not be coming back to it*. What I will be doing in 2017 is working on getting membrane proteins to self-assemble into as large and as regular crystals as possible. This is part of an EU-wide network on membrane-protein crystallisation that will be starting in 2017. Membrane proteins are proteins that live in back-to-back layers of soapy molecules — which is what cell membranes are. Membrane proteins are important as many (by some measures a majority) of drugs target these proteins.
Proteins are big, horribly complicated, and floppy, molecules, and so it is a miracle we can get any of them to crystallise at all. To crystallise they have to fit into a regularly repeating lattice with each protein in lockstep with the others. Membrane proteins are even worse, as the protein spans a complex floppy set of two back-to-back layers of soapy molecules. And so as you would expect, membrane proteins are even harder to crystallise than proteins that live in solution. But because membrane proteins are so important, people try anyway, and often they fail.
Starting this year and running to 2020, the EU will be giving us about €4 million to train up 12 PhD students and do something about this problem; us being a team of 8 EU universities and 1 neutron facility, plus 6 partners that include 2 big multinational pharmaceutical companies.
I am a bit new to membrane-protein crystallisation, so I have been doing some reading up on it. Indeed people are really desperate for the structural information that X-ray diffraction of crystals of membrane proteins can yield. They even resort to using crystals down to around 1 thousandth of a millimetre across, i.e., absolutely tiny, around only 100 molecules across. Because sometimes that seems to be as big as they can make the crystals.
So the problem we will be tackling is both tough and important. I think it is likely that we’ll be making more incremental progress than huge breakthroughs, but I think we have some new combinations of skills to apply. Ultimately, there is only one way to find out, and that is to try our best and to see what happens.
* If you want a beer recommendation, then I also tried a couple of IPAs from Brew by Numbers, which were great.
Chance & Necessity 