I am trying to persuade my final year research project students at The Institute that they are on the home stretch and that they should be wrapping up their analysis and thinking about what colour ribbon they want to tie it up with. As most years, I have a sample of the whole year-cohort: some down to earth, some from Zorg; some needy, some fiercely independent; some focussed, some flakey; all pushing the frontiers of science and learning how to think. On Tuesday, I had to brace a couple of them as they wallowed in an existential crisis: reassuring them that they did know something; that they had given the Frontiers a damned good shove. It is sad really that these young adults aren't more robust. But, on my watch, they get told that they Can Do it; that they are unique in their talents; that there are a rake of things where they are smarter than, say, me. Actually, if research students don't have some sort of crisis about the-meaning-of-it-all, then they probably aren't close enough to the frontier. My old gaffer had a great technique - a retrospective through their lab-books - for demonstrating to her students that they had made a contribution.
My students are still, even after 4-5 months work, absolute beginners so I can usually get an answer to a niggling question quicker than they can. One of my quieter chaps is doing a comparative immunology project, looking at the variation of a handful of inflammatory modulators called acute-phase proteins. I was intrigued by the idea that we humans have only a single C-reactive protein CRP but a handful of serum amyloid-A SAA proteins. Different mammalian species have a different inventory of SAAs [SAA3 is alive and well in mice but that gene on its way out in us] but only one CRP. Is 'singleton CRP' true for all mammals? I asked, could you check in representative species for all / most of the mammalian orders?
Before he started his project he had really no formal idea that mammals can be classified into groups according to their shared attributes. Now he knows that a quarter of all 6,500 species of mammals are rodents and one fifth are bats. Long words like Artiodactyla [cow pig sheep llama camel and whale] and Tubulidentata [aardvark] trip off his tongue now. He showed me a list of mammalian orders and maintained that he couldn't find a CRP in most of them. I looked skeptical and asked if he'd tried homology searching with Blast rather than trawling through the annotation in Uniprot. He's so quiet that I didn't get a clear answer, so I said I'd give it a go myself and get back to him.
homology searching with Blast can be done at the NCBI in Bethesda MD. You send your sequence thither by internet, where a big server-farm compares it to every other sequence in a massive database; sorts the 'hits' in order of similarity and returns the results to your computer. If it's not too busy the answers comes back in a couple of minutes - which would be pretty amazing if we didn't have Google as a benchmark. The NCBI blast server has a really useful option: to limit the output to a particular taxonomy class:
Proboscidea but I'm in such a hurry that I accept Proboscia (taxid:216776) and hit <enter>. Two minutes later a <brrrrrp> No Hits Found message comes back which is really unexpected. Maybe The Quiet Man is correct, I think, maybe CRP is not a universal attribute of the mammalian immune response. But a little dig in the Sloughs of Incredulity reveals that Proboscia alata aka Rhizosolenia alata is quite a bit smaller than an elephant. Because it a diatom - a microscopic [about 50x10μm] alga with a silica impregnated cell wall. The fact that it has a little trunk like an elephant is no evidence for sharing a recent ancestor but it does give rise the the microbes name. Elephants do have [a single] CRP <phew>: if you/I do the analysis correctly. Bit of a <duh> moment for me.