{"id":770,"date":"2010-05-04T21:01:53","date_gmt":"2010-05-04T21:01:53","guid":{"rendered":"http:\/\/occamstypewriter.org\/mindthegap\/2010\/05\/04\/in_which_i_sleep_with_the_enemy\/"},"modified":"2010-05-04T21:01:53","modified_gmt":"2010-05-04T21:01:53","slug":"in_which_i_sleep_with_the_enemy","status":"publish","type":"post","link":"https:\/\/occamstypewriter.org\/mindthegap\/2010\/05\/04\/in_which_i_sleep_with_the_enemy\/","title":{"rendered":"In which I sleep with the enemy"},"content":{"rendered":"

They’re pale and creamy, scattered across the agar like diseased lesions. Something about the three-dimensionality of the colonies – vaguely dome-shaped instead of flat – rings some sort of primordial alarm bell deep in my hindbrain. Although I know it’s irrational, I can’t control the little shiver of revulsion each time I stab one of the glistening disks with a sterile toothpick and spread it over the next pie-shaped zone of the fresh plate. Even the way these yeast people have taught me to streak seems inherently wrong: my Microbiology tutors at university would be horrified by the laissez-faire way I am now scribbling<\/em> onto the surface of the agar, with no system or intent to isolate single colonies. <\/p>\n

\nOf course I am thrilled that all of my transformations yielded so many resistant colonies, but to this biomedical researcher, yeast are only ever bad news: they infest your tissue culture cells, grow inappropriately on your bacterial plates and cause all manner of nasty infections in patients. <\/p>\n

\nSo, after months of sitting in front of a computer, I’m finally back at the bench. Just today I hit the shiny ‘submit’ button that should consign my further revised manuscript to its final acceptance (seeing as how the editor had only asked for minor text changes); and after a visit from my collaborator last week, it was clear I couldn’t proceed further on data analysis until he’d performed a few more bioinformatical dark arts with our dataset. All this meant that I was free to escape to something more interesting in the interim.<\/p>\n

\nSo escape I did, to my lovely new collaboration with the local Schizosaccharomyces pombe<\/i> guys down on the first floor. Even after a few days with this crew, I am starting to suspect that fission yeast people are inherently cooler than your average biologist. For starters, they listen to music in blatant disregard to institute rules – not loud enough to trouble anyone, but just loud enough to give off a rebellious vibe. And of course, the entire place smells faintly of beer.<\/p>\n

\nIt’s a brave new world: I’ve just made a series of mutants of the pombe homologue of one of the most promising novel hits from my cell shape screen. In one week, you can knock out your gene; you can replace it with a tagged version of your gene under its endogenous promoter; and you can put in a version of your gene under an inducible promoter, all down to the magic of recombination. We made monster recombination cassettes using 100-mer PCR primers and then just zapped them into the bugs – the pombe did the rest. I estimate that it’s taken me ten days to achieve something that would have taken two to three years in a mouse.<\/p>\n

\nIt’s already exciting: I can see that my deletion mutant transformant colonies are noticeably smaller than the wild-type, so there might be some sort of effect on growth. In a few days I’ll be able to peer down a microscope and visualize the tagged protein to see where it is localized in the cell, and I’ll be able to look at the knockout and overexpressing cells in more detail to see if I can discern the nature of the defect. Of course once I have a clue about pathways, there is an entire genomic library of yeast strains that I can mate my new strains with, to look for genetic interaction all in a matter of a few days.<\/p>\n

\nAnd the best bit? By convention, I get to name these new yeast strains after my own initials, and they will pass forever into the global community’s strain collection. JLR-1, -2, -3 and -4 may not be as exciting or poetic as a Drosophila gene name, but it’s a hell of a lot more personal.<\/p>\n","protected":false},"excerpt":{"rendered":"

They’re pale and creamy, scattered across the agar like diseased lesions. Something about the three-dimensionality of the colonies – vaguely dome-shaped instead of flat – rings some sort of primordial alarm bell deep in my hindbrain. Although I know it’s … Continue reading →<\/span><\/a><\/p>\n","protected":false},"author":6,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-770","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"_links":{"self":[{"href":"https:\/\/occamstypewriter.org\/mindthegap\/wp-json\/wp\/v2\/posts\/770","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/occamstypewriter.org\/mindthegap\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/occamstypewriter.org\/mindthegap\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/occamstypewriter.org\/mindthegap\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/occamstypewriter.org\/mindthegap\/wp-json\/wp\/v2\/comments?post=770"}],"version-history":[{"count":0,"href":"https:\/\/occamstypewriter.org\/mindthegap\/wp-json\/wp\/v2\/posts\/770\/revisions"}],"wp:attachment":[{"href":"https:\/\/occamstypewriter.org\/mindthegap\/wp-json\/wp\/v2\/media?parent=770"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/occamstypewriter.org\/mindthegap\/wp-json\/wp\/v2\/categories?post=770"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/occamstypewriter.org\/mindthegap\/wp-json\/wp\/v2\/tags?post=770"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}