Welcome to the next episode of the WOrM Podcast 🪱Today we’re looking at a paper that doesn’t answer a biological question.Instead, it builds the tools to answer thousands of biological questions in the future.The ambition?To fluorescently tag every protein encoded by the C. elegans genome. ⸻🧬 The big ideaWe already have remarkable gene expression atlases based on RNA.But RNA isn’t the whole story.Proteins are the molecules that actually perform the work inside cells, and protein abundance often doesn’t match RNA abundance.The authors argue that the next frontier is a whole-animal protein atlas showing exactly where every protein is found, in every cell, throughout development. ⸻🔬 How did they test the concept?Rather than tagging one gene at a time, they asked a much bigger question.Could they tag three genes simultaneously using CRISPR?They selected:30 genesthree different fluorescent proteins10 pooled CRISPR experimentsThe approach worked remarkably well.They successfully generated 24 of the 30 tagged proteins, with all successful tags visible by fluorescence microscopy. ⸻🌈 Why three colours?Each fluorescent protein was chosen for a different brightness and wavelength.The clever part was matching fluorophore brightness to expected protein abundance.Highly expressed proteins received one fluorophore.Moderately expressed proteins another.Low-abundance proteins received the brightest red fluorophore, which also suffers least from worm autofluorescence.This makes large-scale screening much faster and more practical. ⸻🧠 The biology was the surpriseAlthough this is primarily a methods paper, it immediately produced biology.Several proteins appeared in tissues where RNA datasets suggested they should not be enriched.Examples included proteins accumulating preferentially in:germlinegonadal sheathspermspecific neuronsglial cellsThese differences highlight something important.RNA tells you what might be made.Protein localisation tells you what is actually there. ⸻🚀 Why this mattersAround 8% of the C. elegans proteome has already been tagged.At the current pace, completing the remaining genome could take around 100 years.Pooling multiple CRISPR edits into single experiments could reduce that dramatically and make a community-wide effort realistic. ⸻🧠 The bigger pictureImagine being able to ask:Where is every protein expressed?Which cells use it?Where inside the cell does it go?How does localisation change during ageing, stress or disease?Instead of studying one protein at a time, researchers could explore an entire organism with single-cell resolution.That’s the long-term vision behind this work.⸻🧠 The take-home messageSometimes the most important papers don’t make a discovery.They build the infrastructure that allows everyone else to make discoveries.If the C. elegans community succeeds in creating a complete fluorescent proteome atlas, it would become one of the most valuable biological resources ever generated for any multicellular organism.⸻📄 Paper discussedEroglu M., Hobert O. (2026)A pilot study for whole proteome tagging in C. eleganseLifeDOI: 10.7554/eLife.110717.3If you enjoyed this episode, please like, follow and subscribe wherever you listen to the WOrM Podcast ⭐🎧 It really helps others in the community find the show.This podcast is generated with artificial intelligence and curated by Veeren. If you’d like your publication or product featured on the show, please get in touch.📩 More info:🔗 www.veerenchauhan.com📧 [email protected]

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