merklinglab.bsky.social
We are all about mosquitoes, viruses and single cells!
Insect Infection and Immunity - Merkling Lab
@CNRS.fr @Pasteur.fr @ERC.europa.eu
#newPI #DiversityEquityInclusion #ally 🏳️🌈🏳️⚧️
https://aedes-cell-atlas.pasteur.cloud/
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Congratulations on getting the poster prize !! 🥳
Also very nice meeting you at the conference :)
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@sebbontempsgallo.bsky.social , Chercheur @cnrs-hautsdefrance.bsky.social @cnrsbiologie.bsky.social
Maladie de #Lyme : comment s’en protéger ?
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That's amazing - congratulations to you all!
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This is super cool - very much looking forward to reading the pre-print and the book. Congratulations to all of you for an another amazing study, it makes me miss the Drosophila field even more ;)
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Thank you! I would be curious to know more about that indeed.
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I would also like to thank our institutions and funders, @pasteur.fr @cnrsecologie.bsky.social @agencerecherche.bsky.social @ird-fr.bsky.social @sorbonne-universite.fr @upcite.bsky.social @unistra.fr @frm-officiel.bsky.social for making all of this possible.
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But foremost, I would like to thank Louis @lambrechtslab.bsky.social for bringing me on to such a scientific adventure, riding out all the project's ups and downs through a world pandemic, and helping with pushing this over the finish line together with @elodiecouderc.bsky.social.
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Of course, so many questions remain. But for now, I thank everyone that poured time and energy into this project. Many members of @lambrechtslab.bsky.social, Anna and @elodiecouderc.bsky.social - our Bioinformatics Core, and most of all Davy, Christophe and Diego who first found those wonderful 🦟.
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Finally, Anna bravely generated Bakoumba mosquito sub-populations. One that contains the 18-bp deletion, and one that doesn't. We then infected these lines with DENV-1 and DENV-3 and confirmed that this deletion was sufficient to alter mosquito susceptibility to virus infection.
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We sequenced hundreds of mosquitoes and found a recurring 18-bp deletion in the CYP4g15 promotor region of some mosquitoes. This deletion correlated with CYP4g15 expression levels. A jaw-dropping result obtained by Elodie and Anna.
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During the entire project, we kept noticing that CYP4g15 expression levels were very variable between mosquitoes and asked whether those differences could be linked to mutations in the gene's sequence. A wild guess, really.
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Next, Anna and Eric created mosquito lines that ubiquitously overexpressed CYP4g15 and confirmed the gene's role upon DENV infection. When it is present at high levels, it prevents mosquitoes from being infected ! This was an amazing result. And, it also works for DENV-3.
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I knocked-down 40 individual genes using RNAi and assessed whether they altered DENV infection levels. About a year and gazillions mosquitoes later, I found that CYP4g15 had a strong and consistent impact on DENV. Upon gene knock-down, infection rates were significantly increased.
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The project started when we found that mosquitoes from Bakoumba, Gabon were able to resist DENV-1 infection. The resistance occured within midguts, and using single-midgut RNA-seq, we got a list of candidate genes that could underlie this phenotype.
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@pasteur.fr @erc.europa.eu @cnrsecologie.bsky.social @unesco.org
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I’m going to look for my copy of « Lords of the Fly » to dive back into this - the book is partly on Google books: books.google.com/books/about/...
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My favorite part was his incredible knowledge of drosophila research history, going back to anecdotes about Morgan, Bridges, Lewis and Beadle. He made us feel like descendants of this great scientific epopee and at the same acknowledged the imposter syndrome that we unavoidably carry. (4/4)
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I found back a picture of Scott, Casey, and the late Michael Ashburner from back then. I also found my notes from his lectures and they are full of funny jokes and comments that reflect how insightful, impressive and witty his was. (3/4)
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I had the privilege to attend the Drosophila genetics and genomics course in Cambridge back in the summer of 2012, and together with @caseybergman.bsky.social , Scott made these 2 weeks unforgettable to the young PhD student I was. (2/4)
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This is great story, thank you for sharing.
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Hi there :) this is super super cool - would it work for non-model organisms and less well annotated genomes such as those of mosquitoes ?
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And - there is almost no expression in the fat body, expect for the granulocytes that were associated with the tissue !
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I had to go see where Hsc-70-3 is located in our midgut cell atlas (aedes-cell-atlas.pasteur.cloud) and it is well expressed in a sub-population of enterocytes (EC4) and cardia cells !
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Congratulations to all co-authors on finding Hsc-70-3 as a DENV receptor in the mosquito midgut ! Amazing that is is the ortholog of the P47 receptor, a midgut receptor in Anopheles gambiae that interacts with the Plasmodium falciparum surface protein Pfs47 !