Sarah Merkling
@merkling_lab
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Mosquitoes, viruses and single cells Research lab @CNRS @InstitutPasteur @ERC_Research #newPI #DiversityEquityInclusion 🏳️🌈🏳️⚧️ @merklinglab.bsky.social
Paris, France
Joined June 2009
Stop for a second and imagine: a heat shock protein relocalizes to the cell surface and mediates dsRNA binding and internalization! Intrigued? Read our newly minted paper in @ScienceAdvances
https://t.co/v7e3qg9T5H Congrats to all the authors and thanks to reviewers and editor!
science.org
Hsc70-4 localizes to the cell surface of Drosophila cells, binds to exogenous dsRNA, and mediates its internalization.
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I would also like to thank our institutions and funders, @institutpasteur @CNRS @AgenceRecherche, @SorbonneParis1, FRM, IRD, UPCité, @unistra for making all of this possible.
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But foremost, I would like to thank Louis @LambrechtsLab 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 @couderc_elodie
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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, @CRISPRqueen, @couderc_elodie, Eric Marois, @C3BIPasteur and Christophe, Davy and @d_ayalag who first found those wonderful🦟
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Finally, @CRISPRqueen bravely generated Bakoumba mosquito sub-populations. One that contains the 18-bp deletion, and one that doesn't. We infected these lines with DENV-1 and -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 @couderc_elodie and @CRISPRqueen
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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, @CRISPRqueen 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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Happy to share our work exploring the genetic basis of dengue susceptibility in Aedes aegypti and revealing the antiviral role of a cytochrome P450. https://t.co/gtvjylA20y It had been a long and wild ride that started back when I was a postdoc with @LambrechtsLab ! A thread ⬇️
biorxiv.org
The mosquito Aedes aegypti is the primary vector for dengue virus (DENV), which infects millions of people annually. Variability in DENV susceptibility among wild Ae. aegypti populations is governed...
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Really proud of the team for the launch of our new website: https://t.co/Ve5kwL50Dg A ton of hard work went into this and we think it's pretty good :-) An excellent start to our 20th anniversary year!
embolableadership.org
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Happy Women & Girls in Science day to you all - girls, women & allies that love science and advocate for making it an increasingly diverse and attractive place. Let's imagine a future with more women in science & better research that truly serves and represents us all 💜 @UNESCO
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🎉 Bravo à @michaelwhite_36, chercheur à l’Institut Pasteur, lauréat de l'ERC Consolidator Grants ! Son projet ULTIMASero explore les maladies infectieuses via des tests multiplex, études épidémiologiques et modélisation statistique.
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This is @TomPVial second year being a Workshop Conference Lead @EMN_MetSoc, I can only recommend joining this very lively and friendly bunch of early career researchers ! @institutpasteur @IbeidLabex
Highlighting @EMN_MetSoc member + Workshop Conference Lead, @TomPVial. Thomas holds a PhD in Microbiology + is focused on insect #metabolomics. He works as a postdoc @InstitutPasteur, combining single-cell transcriptomics + metabolomics to explore mosquito-virus interactions #ECR
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This might one of my last posts over here, figured I'd give it a few more days until the migration is complete. See you all on the other side!
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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 ( https://t.co/WhpASYqbO8) 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!
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