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Jacki Heraud-Farlow Profile
Jacki Heraud-Farlow

@jacki_hf

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Team leader at CiiiD Hudson institute . A-to-I RNA editing, dsRNA, auto-inflammatory disease. Mum 👧🏼👧🏼👧🏼. Views are my own. She/her.

Melbourne, Victoria
Joined May 2019
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@jacki_hf
Jacki Heraud-Farlow
7 months
Time for a 🧵 on our new paper from the Walkley lab. If you're into RNA editing by ADARs, double-stranded RNA (dsRNA) sensing, post-transcriptional gene regulation and CRISPR screening, then read on! 1/X. #RNABiology #InnateImmunity.
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@jacki_hf
Jacki Heraud-Farlow
7 months
RT @scottbscience: 📢 New paper from the lab!. In a fantastic new collaboration with @ana_tufegdzic lab, we characterise a major Pol II home….
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@jacki_hf
Jacki Heraud-Farlow
7 months
RT @inflammasomelab: Have you ever wondered whether pyroptotic corpses have functions beyond the grave? We made the surprising discovery th….
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@jacki_hf
Jacki Heraud-Farlow
7 months
RT @TimGottschalk: If you have a sec, check out our new paper by @Amy_Hsu_ with @HibbsLab (@MonashImmunol) and @ivana_hal (@imgprague) show….
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@jacki_hf
Jacki Heraud-Farlow
7 months
RT @ScienceMagazine: A new @SciImmunology study reveals new pathways regulating the cellular response to unedited double-stranded RNA, whic….
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@jacki_hf
Jacki Heraud-Farlow
7 months
RT @gavinjknott: We are excited to share pre-prints describing a successful foray into ML-driven protein design. With @Rhys__G we designed….
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@jacki_hf
Jacki Heraud-Farlow
7 months
RT @SethCheetham: There are more ways to design an mRNA than atoms in the universe, so how do you choose the best one? Our new @BASEmRNA so….
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@jacki_hf
Jacki Heraud-Farlow
7 months
RT @gjendinevoss: Apply today to present your work and connect with future leaders in RNA biology: And don't forge….
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@jacki_hf
Jacki Heraud-Farlow
7 months
RT @DavidovichLab: Moderna’s first manufacturing site in the Southern Hemisphere has now officially launched here in the Monash Technology….
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@jacki_hf
Jacki Heraud-Farlow
7 months
RT @DraganaV10: What an end to the year! Our work is out in @NAR_Open! 🎉 We mapped #interactomes of both #ADAR1 isoforms during homeostasis….
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@jacki_hf
Jacki Heraud-Farlow
7 months
Massive kudos and thanks to the Walkley lab team @SVIResearch and @CiiiD_Hudson on this project including @AlistairChalk and collaborators including @VCFGconnect, @RNAedit, @QinA2I and @EpiAgeing_lab labs. This is just the highlights, so much more in the paper!.15/15.
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@jacki_hf
Jacki Heraud-Farlow
7 months
Very little is known about GGNBP2 but it has been identified in some cancer studies and GWAS for ALS and other neuro diseases. I suspect/hope we will be hearing more about this interesting protein in the coming years. Would love to hear from others if you’re working on it!.
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@jacki_hf
Jacki Heraud-Farlow
7 months
As mutations in ADAR1 can cause Type I interferonopathies and autoinflammatory disease such as Aicardi-Goutieres syndrome (AGS), our screen has identified new genes like GGNBP2, CNOT10 and CNOT11 as new potential therapeutic targets in #raredisease. 13/X.
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@jacki_hf
Jacki Heraud-Farlow
7 months
. Our model is that in the absence of GGNBP2 the threshold for MDA5 activation is not reached and thus suppresses the pathway. 12/X
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@jacki_hf
Jacki Heraud-Farlow
7 months
The prevailing model is that a set of A-to-I edited RNAs become immunogenic when editing is reduced, and that collectively these increase the dsRNA load to pass the threshold for MDA5 activation. 11/X.
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@jacki_hf
Jacki Heraud-Farlow
7 months
. when we looked at A-to-I edited RNAs, we found a global decrease in their expression in the cytoplasm of GGNBP2 KO cells. We propose that GGNBP2 changes the balance of dsRNA between the nucleus and cytoplasm to control MDA5 activation. 10/X
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@jacki_hf
Jacki Heraud-Farlow
7 months
We also didn’t see any differences in total RNA that would explain the absence of IFN response, including no change in expression of repetitive elements. BUT . 9/X.
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@jacki_hf
Jacki Heraud-Farlow
7 months
So, we did RNAseq on total and cytoplasmic/nuclear RNA to see what was going on. Consistent with the qPCR – we saw virtually no gene expression changes in the GGNBP2 KO following loss of editing and a complete block in ISG induction. 8/X
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@jacki_hf
Jacki Heraud-Farlow
7 months
We showed that MDA5, dsRNA sensing and IFN signalling pathways are slightly attenuated in GGNBP2 KO’s but still largely intact so that can’t explain the rescue. This suggested GGNBP2 was probably acting on the immunogenic RNA itself. 7/X.
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@jacki_hf
Jacki Heraud-Farlow
7 months
Our top hits were GGNBP2, CNOT10 and CNOT11. The three proteins interact and are top co-dependencies in Depmap suggesting a functional link across cell types. Incredibly, KO of GGNBP2 rescues editing-deficient cells even better than KO of MDA5, and completely blocked ISGs! 6/X
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@jacki_hf
Jacki Heraud-Farlow
7 months
We performed a genome-wide CRISPR KO screen to look for outgrowth of KO alleles that would rescue editing deficiency. Surprisingly, 3 genes enriched far higher than all others and had not been previously linked to dsRNA/IFN pathways before! 5/X
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