CLi

>be cell biology postdoc at UCLA, 1986 >job: purify vesicles from rat liver >ez >purify the vesicles >something else in the tube >weird little barrels, way bigger than a ribosome >fkisdis >purify the barrels instead >mostly protein, tiny bit of RNA >not related to vesicles at all >new organelle just dropped? >lab holds a naming contest >"vaults" "sure, "great name" " >write it up, publish >conclusion section: "function: unknown" >surely we'll figure it out in a couple years >reviewers: "are you sure this isn't just a virus" >prove it isn't a virus >apply for grants to study it >first question on every call: "what does it do" >"we're working on it" >be early 90s >vaults hang around the nucleus >"they must plug the nuclear pores" >they do not >be different scientist, Netherlands, 1995 >chasing LRP, mystery protein that shows up in chemo-resistant tumors >clone it >~88% identical to rat vault protein >it was vaults the whole time >whole cancer field piles on >a decade of papers on vaults and drug resistance >nobody ever proves vaults cause it >back at UCLA >one of the vault proteins binds telomerase >"guys what if this is the fountain of youth" >knock it out in mice >telomeres fine, aging fine, mice fine >2002 >knock out the main vault protein >mice: perfectly healthy >knock out all three vault proteins >completely vaultless mice >mice: basically fine, some subtle immune stuff >mfw something in every cell since the dawn of eukaryotes does nothing obvious >"just test it in yeast" >yeast don't have vaults >"worms then" >no vaults >"fruit flies" >no vaults >mfw every easy model organism dropped them >try making recombinant vaults in insect cells >expecting to get some loose protein at best >get fully assembled vaults >can't find a single free copy of the protein anywhere >turns out ribosomes 3D-print the barrel straight off the mRNA >lolwut >still no function >be structural biologists >spend years modeling it as 96 proteins with 8-fold symmetry >2009 X-ray structure >it's 78 proteins, 39-fold >caps still blurry >2025: caps are closed, 13-fold, tiny hole in the middle >still no function >NIH funds vault research for 15 years >NIH: "so what does it do" >"...we're working on it" >NIH stops returning calls >if we can't figure out what it does, we'll make it do something >stuff a cancer-fighting chemokine inside the barrel >inject into mouse lung tumors >immune cells swarm in, tumors shrink >2011: "human trials within three years" >2024: "human trials next year" >2025 database: preclinical >start a YouTube channel explaining vaults to anyone who'll listen >be different scientist, Broad Institute >want to record what genes a cell turned on over time >try tethering mRNA to a bacterial protein >doesn't work >stumble onto a YouTube channel about some obscure barrel organelle >engineer vaults to grab mRNA >RNA half-life goes from ~17 hours to ~132 hours >publish in Science, 2026 >use it to catch drug-resistance genes in lung cancer cells before the drug even hits >the vault guy is thrilled >still nobody knows what vaults are for >be epigeneticists >screen the whole genome for methylation set at random in the early embryo >separately study kids conceived in different seasons in rural Gambia >both screens independently point at the same gene >it's the goddam vault RNA gene >its methylation depends on conditions around conception, locked in for life >linked to cancer outcomes, blood sugar, cleft palate >mfw the mystery barrel has a mystery RNA that remembers when you were conceived >40 years later >one of the most abundant structures in your cells >still not in a single textbook cell diagram >we use it anyway because yolo >function: unknown