Tuesday 15 December 2015

Bigger than a bread-box?

This week, Mon/14 and Tues/15, I'm up in Dublin doing a couple of honest days' work teaching for the TCD MSc in Immunology. Because I spent a decade working in a Comparative Immunology lab, I know some of the language and some of the key concepts but I wouldn't call me an Immunologist. You may call me an evolutionary biologist if you want, though, and I've been trying to transmit that angle, that way of thinking, to these smart young immunologists.  It's quite intense, 2 hours theory in the morning, 3 hours on the interweb in the afternoon using an unfamiliar toolkit to answer some immunological questions. I can't expect, in two busy days, to cover all the information I've internalised during two decades immersed in the field of bioinformatics and molecular evolution. But if they learn one or two things that are new-and-interesting, and maybe later use some parts of the manual which I've written for the course, then I feel it will have been worth talking myself hoarse.

As in a lot of my courses/modules I started them off with a pre-quiz so that they would have a bench-mark to compare against the new things they will learn over the next couple of days. In 2013, I asked that class to put in order of size: a molecule, a macromolecule, a cellular organelle, a cell and a tissue. That turned out to be easy for almost all the Msc students - although it's eye-watering hard for my first year students at The Institute. This year, I thought I'd quantify the question, to further emphasis the relative size of the objects immunologists talk about quite casually - mostly various proteins and various cells - as if everyone is intimately familiar with them.  It's my belief that many scientists compartmentalise their knowledge - ecology is out there in the Serengeti; biochemistry is here on the side-table; genetics and evolution have nothing to do with biochemistry; drug actions have nothing to do with the intestinal flora . . . aNNyway, here's the question:
Q. If this room [5m x 7m x 3m]  was a T-cell [a vital part of the immune response to pathogenic attack]; how big would the T-cell receptor TCR [a key protein embedded in the cell membrane of the T-cell] be?

If you know, or can calculate/guesstimate this ratio, you'll know how many copies of the TCR there are likely to be. You'll also be able to hazard a guess about the number of copies there are of CCR5, another T-cell membrane protein that opens the door for HIV to infect and ultimately kill T-cells. The cartoon [L from Nature Immunology so it has some authority] suggests a ratio of about 1:100. My answer based on a larger classroom in The Institute and some assumptions about the size of the cell was
A. a sultana.

My assumptions were a bit off because a T-cell is a bit smaller at ~15μm than an average cell in diameter. A typical protein is about 7nm across.  So in that room with that cell specified, the answer is more likely to be
A. a grain of rice
But I was a bit nearer than the other people in the room who variously offered:
a raisin; a stapler / a computer mouse; the paper-bin [twice]; a chair seat not the whole chair / 50cm / 10% / a chair; 20% / the door [twice] / the [small] white-board; half the diameter; the office next door; no idea [tsk tsk: damn and blast you have to commit!].  That's a lot of variability, and I think we're all exaggerating.

Why does it matter? Because the scale difference between biochemistry and cell-biology is so enormous that it's impossible to fit in a textbook diagram: if you show a cell at a reasonable size on an A5 page, then the cell's proteins would each be a single pixel wide.  It's like trying make a scale model of the solar system where those attempting the problem say things like "Jupiter is a chestnut, more than a city block from its nearest neighbor in space!" We, all, need to integrate knowledge from across disciplines: specialization is for insects!

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