@MartinPacesa
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>be cell biology postdoc at UCLA, 1986View quoted post on X
>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
“The scroll offered only a shimmer, a veil thinly lifted to my eyes. A future lost. A victory undone. Sands of time scattered by fate.”
Yazar, Moth Priest to High Queen Iradne of Hammerfell (4E 206)View quoted post on X
Nitroduck designs new colors, flavors, and disease resistance into fruits and veggies. We integrate CRISPR into breeding through pollen, making any crop gene-editable.
Breeding a new specialty crop variety takes 8 - 16 years: breeders hope for random gene combinations and mutations, then spend years picking out the good ones. Meanwhile, consumer tastes, the climate trends, and pathogens change way faster.
Now, accessible genome sequencing and AI can tell breeders what to aim for instead of what to hope for, and CRISPR can turn random mutations into chosen ones. The catch is that CRISPR only works on about 15% of crops. It has to go into a single stem cell that’s then regrown into a whole plant, a process that has to be worked out for each variety, which is cost-prohibitive.
We skip the stem cell and put CRISPR into a pollen grain. The grain pollinates a flower, and out comes an edited seed - seamlessly tapping into how breeders already work.
Matúš, Miro, and I are plant synthetic biologists who made duckweed, the smallest and fastest-growing plant on Earth, genetically engineerable. For doing so we won the Grand Prize at iGEM, the “Olympics of biotech.” During our studies, we engineered 4x more plants than the average plant scientist does in a whole career. Now we’re building Nitroduck, The Crop Design Company, which will make pesticides obsolete by 2042.View quoted post on X
