Have you ever wondered how knocking out every single gene in the human genome, one by one, might affect your intracellular pathogen of interest? We did, & boy was it a wild ride! Happy to share our preprint discovering the essential host genome for Cryptosporidium - www.biorxiv.org/content/10.1... - ThreadSky

ghostpathogen.bsky.social • 83 days ago

Have you ever wondered how knocking out every single gene in the human genome, one by one, might affect your intracellular pathogen of interest? We did, & boy was it a wild ride! Happy to share our preprint discovering the essential host genome for Cryptosporidium -

https://www.biorxiv.org/content/10.1101/2024.12.04.626561v1

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ikinglab.bsky.social•82 days ago

Wow! I can’t wait to see where this gets published. Congrats!

ghostpathogen.bsky.social•83 days ago

We found some cool host cell biology, perhaps even cooler (*gasp*) parasite biology, and hopefully a new treatment for Cryptosporidiosis.

If you’re unfamiliar, Cryptosporidium (‘Crypto’) is an intracellular parasite causing intestinal disease, particularly severe in infants & immunocompromised. 2/

ghostpathogen.bsky.social•83 days ago

It’s a major cause of diarrheal disease - there's no vaccine and only one approved drug that doesn’t really work.

We hoped learning more about what the parasite needs from its host cell might lead to different treatment options. Also maybe even some cool cell biology! We were not disappointed. 3/

ghostpathogen.bsky.social•83 days ago

It all started with the High Throughput Screening facility @thecrick.bsky.social – they had a full-genome arrayed library of Cas9 crRNA guides to knock out genes individually well-by-well, as opposed to the more traditional pooled gene knockout approach...

4/

ghostpathogen.bsky.social•83 days ago

This arrayed system also meant one can image each well with a different gene knocked out, opening up a range of infection phenotypes to study in the same well.
A whole genome CRISPR screen combined with high content microscopy – it was a cell biologist’s match made in heaven! 🤩
5/

ghostpathogen.bsky.social•83 days ago

They were looking for a lab to try out this new system… it was mid-2020 and we in the newly-minted @saterialelab.bsky.social were equal parts bright-eyed and isolated from sensible science society enough to think this could work...

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ghostpathogen.bsky.social•83 days ago

We also thought Cryptosporidium was a perfect candidate for this expansive (and expensive) approach, since so little is known about the cell biology of infection of this intracellular parasite.

If this worked, it would be worth it for the whole crypto community.

7/

ndemiguel.bsky.social•82 days ago

Absolutely amazing!

andcoat.bsky.social•83 days ago

Awesome research. I love that such great science pops up in my feed for a Friday afternoon read.

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