Geoff Faulkner @Faulkner_Lab Twitter profile

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Geoff Faulkner

8 months

After years of telling visitors to Brisbane what an awesome place it is for fun* adventures, I've decided to make a list in the order I remember them of my favourite places to go for ease of reference. Here goes ... (*definition of fun may vary)

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Geoff Faulkner

@Faulkner_Lab

3 years

Our paper refuting earlier claim of SARS-CoV-2 genomic integration is now online @CellReports The virus does not enter human DNA The same would be true of COVID-19 mRNA vaccines Particular thanks to @UQ_SCMB authors for SARS-CoV-2 experiments @UQ_News

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Geoff Faulkner

@Faulkner_Lab

1 year

Recent @CellCellPress study claiming HERVK transcription drives senescence has a fundamental RNA-seq analysis problem. The results don't show HERVK elements with intact Env are derepressed, nor are they differentially expressed in senescent cells. 🧵 1/n

Resurrection of endogenous retroviruses during aging reinforces senescence

Liu and colleagues uncover the ways in which derepression of human endogenous retrovirus triggers cellular senescence and tissue aging; the findings provide fresh insights into therapeutic strategies...

www.cell.com

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Geoff Faulkner

@Faulkner_Lab

3 years

Our manuscript reporting long-read @nanopore sequencing of SARS-CoV-2 infected HEK293T cells is now available as a preprint. It is work we did with some reluctance but given the context of the global pandemic it seemed obligatory.

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Geoff Faulkner

@Faulkner_Lab

2 years

I have posted this Contradictory Results to bioRxiv: Re-analyzing RNA-seq data from this Neuron paper, I found the claimed L1 upregulation in ataxia telangiectasia (AT) cerebellum is due to an apparent RNA-seq batch effect. 1/n

Elevated L1 expression in ataxia telangiectasia likely explained by an RNA-seq batch effect

A recent study (Takahashi et al., Neuron , 2022) concluded LINE-1 (L1) retrotransposon activation drives cerebellar ataxia and neurodegeneration. This position was based on L1 upregulation in ataxia...

www.biorxiv.org

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Geoff Faulkner

@Faulkner_Lab

3 years

The transposable elements (TEs) field has a steep literature learning curve and it's easy to miss key work (for me too). Kazazian's 2004 Science piece got me into the world of TEs. Here's a few of my favourites from the field over the last 5 years ...

Mobile Elements: Drivers of Genome Evolution

Mobile elements within genomes have driven genome evolution in diverse ways. Particularly in plants and mammals, retrotransposons have accumulated to constitute a large fraction of the genome and...

www.science.org

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Geoff Faulkner

@Faulkner_Lab

2 years

Long-read @nanopore ONT sequencing 👇has lately changed my scientific life. It is an unprecedented tool to study retrotransposons (mobile DNA) and how they are regulated. Here's some examples to show what I mean: 🧵1/n

Nanopore sequencing makes it possible to decode the sequence of DNA and RNA

How nanopore sequencing has revolutionised DNA and RNA sequencing

whatisbiotechnology.org

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Geoff Faulkner

@Faulkner_Lab

3 years

Preprint claiming SARS-CoV-2 integration by L1 RT into human cells has now been contributed to PNAS. The authors have added ONT sequencing data and find an example of a potential SARS-CoV-2 integrant on chrX. Some thoughts about this: 1/n

Reverse-transcribed SARS-CoV-2 RNA can integrate into the genome of cultured human cells and can be...

Prolonged detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and recurrence of PCR-positive tests have been widely repor...

www.pnas.org

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Geoff Faulkner

@Faulkner_Lab

4 years

Our study published today @MolecularCell uses long read @nanopore sequencing and new analysis tools from @_adamewing to interrogate transposon insertions and methylation in human tissues and cancer @SethCheetham @MaterResearch @QldBrainInst

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Geoff Faulkner

@Faulkner_Lab

3 years

Deniz et al (Nat Commun, 2020) is one of the best papers to come out of the TE field in recent years, and an (unusual?) example of work that looks even better when examined closely. It shows how endogenous retrovirus (ERVs) enhance oncogenes in AML. 1/n

Endogenous retroviruses are a source of enhancers with oncogenic potential in acute myeloid...

Nature Communications - Transposable elements are a potential source of transcriptional regulators, but how these sequences contribute to oncogenesis remains poorly understood. Here, the authors...

www.nature.com

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Geoff Faulkner

@Faulkner_Lab

4 years

Our study using @nanopore ONT sequencing to survey transposable element (TE) insertions and methylation landscapes in human tissues is now in print @MolecularCell . Detailed thread 👇 Open access link: Work funded by @nhmrc @CSL @materfoundation 1/n

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Geoff Faulkner

@Faulkner_Lab

2 years

Our study of endogenous retrotransposition during mouse iPSC generation, why it happens, and how it can be prevented, is now online @NatureComms 🥳🥳 Particular credit to @Patricia_Grds @RichardsonL1Lab @_adamewing @ry_lister Sue Mei Lim and Jose Polo

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Geoff Faulkner

@Faulkner_Lab

4 years

For analysing retrotransposon expression using RNA-seq I would recommend TEtranscripts from @MollyHammell . The results are very similar to what I get using my own in house scripts but there is a maintained GitHub and it works well.

GitHub - mhammell-laboratory/TEtranscripts: A package for including transposable elements in...

A package for including transposable elements in differential enrichment analysis of sequencing datasets. - mhammell-laboratory/TEtranscripts

github.com

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Geoff Faulkner

@Faulkner_Lab

2 years

Is L1 retrotransposon activity in the brain specific to only some neuronal lineages? Check out our new preprint👇where we find L1 is activated by the SOX6 transcriptional program of parvalbumin (PV) GABAergic interneuron development. 1/n

LINE-1 retrotransposon activation intrinsic to interneuron development

Transposable elements (TEs) are a reservoir of new transcription factor binding sites for protein-coding genes[1][1]–[3][2]. Developmental programs that activate TE-derived regulatory elements could,...

www.biorxiv.org

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Geoff Faulkner

@Faulkner_Lab

2 months

Pleased our study led by @gabriela_bodea of L1 activity in mouse parvalbumin (PV) interneurons has now been published @NatureNeuro Props also to @JuanManuelBotto @eugeniaferreiro @FranciscoJSL2 @anthonyjhannan + all the authors A brief recap 🧵👇 1/n

LINE-1 retrotransposons contribute to mouse PV interneuron development

Nature Neuroscience - LINE-1 retrotransposons are a type of mobile DNA element normally repressed in the body. Here the authors show that LINE-1 sequences can jump in mouse parvalbumin interneurons...

www.nature.com

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Geoff Faulkner

@Faulkner_Lab

5 years

Our new story on L1 repression by YY1 in humans is out at @MolecularCell . Young L1 families need to escape YY1-mediated methylation to jump, including in brain. L1 also needs YY1 to make full-length, mobile progeny. Relationship maybe maintained for >70Myr

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Geoff Faulkner

@Faulkner_Lab

1 year

Recent @NatureGenet study uses Illumina sequencing to call ~50K mobile element variants (MEVs) in ~3,700 Genomes from 1000GP and BioBank Japan cohorts, then uses these for GWAS and other genome-wide analyses. I have two major criticisms: 1/n

Mobile element variation contributes to population-specific genome diversification, gene regulation...

Nature Genetics - MEGAnE is a new tool to detect and genotype mobile element variants (MEVs) from short-read whole-genome sequencing datasets. Genetic analyses implicate MEVs as population-specific...

www.nature.com

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Geoff Faulkner

@Faulkner_Lab

4 months

Postdoc advertised in my lab to study mobile DNA in mammalian genomes. Permanent position with superannuation and tax concessions in addition to advertised salary. Would suit someone straight out of PhD or a more experienced staff scientist. Please RT

Postdoctoral Fellow - Genome Plasticity & Disease Group - Woolloongabba, Brisbane (AU)

Mater Research is looking for a Postdoctoral Fellow - Genome Plasticity & Disease Group to join the team!

www.nature.com

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Geoff Faulkner

@Faulkner_Lab

2 years

A Nature family journal that I think deserves praise for most of the transposable element (TE), or TE-related, work they have been publishing over the last year is @NatureComms . Here's a few of my favourites, in no particular order: 1/n

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Geoff Faulkner

@Faulkner_Lab

1 year

Important @Nature study today showing ERV envelope (Env) protein expression is at least predictive of outcome for lung adenocarcinoma (LUAD), and appears to influence improved response to therapy. 1/n

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

Nature - In lung adenocarcinoma, antibodies against endogenous retroviruses promote anti-tumour activity, and expression of endogenous retroviruses can predict outcomes of immunotherapy.

www.nature.com

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Geoff Faulkner

@Faulkner_Lab

7 months

My pick for "the" mobile DNA paper of 2023 is actually two studies published back-to-back @Nature reporting the long-sought structure of L1 ORF2p _and_ fundamental insights into the mechanism by which L1 jumps. Amazing work. 1/n

Structures, functions and adaptations of the human LINE-1 ORF2 protein

Nature - X-ray crystallography, cryo-electron microscopy, structural modelling, biochemistry, cell biology, and evolutionary analysis enable characterization of ORF2p, the reverse transcriptase of...

www.nature.com

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Geoff Faulkner

@Faulkner_Lab

1 year

Excellent paper out today in Nature from @GenomeDoctor reporting somatic retrotransposition in normal cells - mainly colon - and tumours. The analyses are rigorous, and say much about L1 mobility (and a bit of Alu) during early human development. 1/2

Widespread somatic L1 retrotransposition in normal colorectal epithelium

Nature - This study illustrates long interspersed nuclear element-1 retrotransposition-induced somatic mosaicism in normal cells and provides insights into the genomic and epigenomic regulation of...

www.nature.com

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Geoff Faulkner

@Faulkner_Lab

2 years

Our single-cell WGS study reporting L1 retrotransposition during macaque brain development published @genomeresearch . Work led by @VictorBillon1 Jay Rasmussen @FranciscoJSL2 @gabriela_bodea and in collaboration with @_adamewing @Carbone_Lab labs 1/n

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Geoff Faulkner

@Faulkner_Lab

2 years

Very recent @NatureGenet study on methylation-restricted TF binding to genes and IAP retrotransposons. This got my attention: in vitro, DNMT TKO neurons expressed 268x more IAP than WT neurons, which had almost no IAP transcripts, measured by RNA-seq. 1/n

Evidence that direct inhibition of transcription factor binding is the prevailing mode of gene and...

Nature Genetics - Co-deletion of all proteins with a functional methyl-CpG-binding domain does not impact genes or repeats silenced by DNA methylation. Analysis of chromatin accessibility and...

www.nature.com

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Geoff Faulkner

@Faulkner_Lab

1 year

Interesting preprint from Ecker and Ren labs using single-cell multiomics to call candidate cis-regulatory elements (cCRE), including in transposable elements (TEs), in human, macaque, marmoset and mouse cortex. A few ideas for potential improvements: 1/n

Comparative single cell epigenomic analysis of gene regulatory programs in the rodent and primate...

Sequence divergence of cis- regulatory elements drives species-specific traits, but how this manifests in the evolution of the neocortex at the molecular and cellular level remains to be elucidated....

www.biorxiv.org

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Geoff Faulkner

@Faulkner_Lab

2 years

Major update to our Nanopore-DamID preprint by @SethCheetham @YohaannJafrani : we simultaneously surveyed CTCF binding and DNA methylation on single molecules, using a DamN126A mutant in HEK293T cells. CTCF clearly binds unmethylated alleles, eg XIST 👇 1/3

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Geoff Faulkner

@Faulkner_Lab

3 years

Review written with @tashjansz published today @GenomeBiology . We dissect the role(s) endogenous retroviruses and other TEs play in cancer, and their therapeutic potential. Some amazing work being done in this space but need improved resolution on TEs

Endogenous retroviruses in the origins and treatment of cancer - Genome Biology

Endogenous retroviruses (ERVs) are emerging as promising therapeutic targets in cancer. As remnants of ancient retroviral infections, ERV-derived regulatory elements coordinate expression from gene...

genomebiology.biomedcentral.com

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Geoff Faulkner

@Faulkner_Lab

5 years

Preprint from @geochurch lab is interesting. #crispr editing thousands of L1 sites without killing human cells. We have tried this in mice repeatedly (adding STOP to mobile L1s) to assess neuro phenotype and failed to get live young. Could be very useful!

Enabling large-scale genome editing by reducing DNA nicking

To extend the frontier of genome editing and enable the radical redesign of mammalian genomes, we developed a set of dead-Cas9 base editor (dBEs) variants that allow editing at tens of thousands of...

www.biorxiv.org

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Geoff Faulkner

@Faulkner_Lab

2 months

Grateful to receive an @nhmrc Investigator Grant (L2). Thank you to the staff and students in my lab who made this possible, and to the reviewers for taking the time to write some nice comments. We'll make the most of the opportunity! List of awardees 👇

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Geoff Faulkner

@Faulkner_Lab

1 year

My re-analysis of the Takahashi et al L1-drives-AT study has now been published as a Letter by @NeuroCellPress , along with a reply from the authors. I hope this is useful, particularly to anyone considering strategies to treat AT in the future. 1/n

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Geoff Faulkner

@Faulkner_Lab

4 years

@nhmrc urgent now to implement equal funding success rates for male and female Ideas and Investigator Grant applicants, starting with the open Ideas Grants round. Women will be unequally affected by COVID-19 shutdown, now is the time to guarantee a fair go to all applicants. 1/2

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Geoff Faulkner

@Faulkner_Lab

2 years

Our new study surveying the acquired mutational landscape of mouse induced pluripotent stem cells (iPSCs) is now a preprint. Work led by @Patricia_Grds and Sue Mei Lim. Collaboration with Jose Polo lab and @_adamewing @RichardsonL1Lab @ry_lister 1/n

Retrotransposon instability dominates the acquired mutation landscape of mouse induced pluripotent...

Induced pluripotent stem cells (iPSCs) may differentiate into any cell of the body and as such have revolutionized biomedical research and regenerative medicine. Unlike their human counterparts,...

www.biorxiv.org

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Geoff Faulkner

@Faulkner_Lab

10 months

Recent study claims repeat transcript abundance in cell-free RNA (cfRNA) from plasma can discriminate pancreatic cancer vs normal samples. I have some concerns about apparent RNA quality differences between the two groups: 1/n

Profiling of repetitive RNA sequences in the blood plasma of patients with cancer

Nature Biomedical Engineering - RNAs derived from transposable elements and other repeat elements are enriched in the cell-free transcriptome of patients with cancer and can serve as diagnostic...

www.nature.com

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Geoff Faulkner

@Faulkner_Lab

3 years

I should add we have more deeply ONT sequenced (53x, 40kbp N50) HEK293T cells infected with SARS-CoV-2, at a higher MOI than this study, and found absolutely no alignments to the relevant SARS-CoV-2 isolate genome using minimap2. Nothing. 5/n

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Geoff Faulkner

@Faulkner_Lab

5 years

Four papers from my lab published over the past year looking at DNA methylation applied to young L1 retrotransposons in somatic tissues (inc. cancer), early embryo and neurodiff: 1/n

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Geoff Faulkner

@Faulkner_Lab

2 years

Very interesting preprint reporting 1250 somatic L1 insertions detected with WGS of ~900 single-cell clones, mostly from human epithelium and fibroblasts. The core dataset looks robust (pending supplement availability) and allowed source L1 tracing. 1/n

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Geoff Faulkner

@Faulkner_Lab

1 year

Elegant and careful experiments from the Moran and Miyoshi labs showing, amongst other things, that L1 RNA expression - and not cDNA - triggers an interferon response. See Fig. 2F below: no difference in IFN-a for WT vs RT- L1 reporter expression.

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Geoff Faulkner

@Faulkner_Lab

4 years

Whether L1 has global insertion site preference is something that I struggle to assign a neat answer to. One of the most interesting findings in this recent comprehensive L1 pan cancer study is a enrichment for somatic L1 insertions in open chromatin. 1/n

Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotra...

Nature Genetics - An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of...

www.nature.com

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Geoff Faulkner

@Faulkner_Lab

1 year

Yesterday's Nature paper on somatic L1 retrotransposition in colon tells us more about the chr13q12.3 source L1 we have been studying for years in the brain: 1/n

Widespread somatic L1 retrotransposition in normal colorectal epithelium

Nature - This study illustrates long interspersed nuclear element-1 retrotransposition-induced somatic mosaicism in normal cells and provides insights into the genomic and epigenomic regulation of...

www.nature.com

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Geoff Faulkner

@Faulkner_Lab

2 years

Postdoc vacancy in my lab in sunny Brisbane - please RT. You will have or soon have a PhD on mobile DNA or a closely related topic. 3+ years to work together on anything we both find interesting. Start within the next year. Overseas applications welcome.

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Geoff Faulkner

@Faulkner_Lab

1 year

Some quick thoughts on a "best practice" approach to find and measure transcripts with potential to express HERVK proteins: 1/n (not saying this is the only way - please comment)

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Geoff Faulkner

@Faulkner_Lab

4 years

Our latest preprint applies @_adamewing 's new TLDR software, for retrotransposon mapping and methylation analysis using Oxford @nanopore long read sequencing, to a set of human tissues. Wonderful tech. @SethCheetham

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Geoff Faulkner

@Faulkner_Lab

3 years

Great papers in this special issue, and more to come!

Genome Biology

@GenomeBiology

3 years

Editorial from our Guest Editor @Faulkner_Lab introducing our latest special issue on the genomics of regulatory elements. The editorial highlights the first tranche of publications in the issue, which can be found here:

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Geoff Faulkner

@Faulkner_Lab

2 years

Interesting recent paper @NatureComms showing LTR5_Hs (HERVK) act as regulatory elements in human primordial germ cells (and hPGC-like cells). Had a close look (signed review) and it is well done. Demethylation on LTR5_Hs in PGCs is surprisingly strong.

Human reproduction is regulated by retrotransposons derived from ancient Hominidae-specific viral...

Nature Communications - The transcription factor network required for primordial germ cell (PGC) specification is known to diverge in mammals. Here the authors show that hominidae-specific...

www.nature.com

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Geoff Faulkner

@Faulkner_Lab

8 months

Last day of #EMBOMobileGenome . What a great program and location! Well done @DeborahBourchis @juliusbrennecke

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Geoff Faulkner

@Faulkner_Lab

1 year

Preprint from @JakobssonLab characterising L1 retrotransposon transcripts in human brain. Includes some important data for the field and the lncRNA phenotype in brain organoids is intriguing. I had a few thoughts about the L1 sense transcript data: 1/n

L1 retrotransposons drive human neuronal transcriptome complexity and functional diversification

The genetic mechanisms underlying the expansion in size and complexity of the human brain remains poorly understood. L1 retrotransposons are a source of divergent genetic information in hominoid...

www.biorxiv.org

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Geoff Faulkner

@Faulkner_Lab

5 years

Recent Genome Res paper from Jorde lab estimating heritable retrotransposition rate in human pedigrees is rigorous and worth reading. Nearly 600 people across 3 generations analysed with 30x WGS to find de novo L1, Alu and SVA insertions in offspring. 1/n

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Geoff Faulkner

@Faulkner_Lab

5 years

Hard to see so many people scored as excellent or outstanding missing out on Investigator Grants. Since 2009, @nhmrc funding has increased at annual indexation of ~1.5%, versus inflation of ~2.1%. In real terms, NHMRC budget has decreased 7% over the last decade 1/n

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Geoff Faulkner

@Faulkner_Lab

3 years

Read this @Nature paper with great interest. It concluded profound/severe de-repression of TEs in Polycomb/Ezh2 conditional knock out (CKO) female primordial germ cells (PGCs): I downloaded and re-analyzed the RNA-seq data and this is what I found: 1/n

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Geoff Faulkner

@Faulkner_Lab

1 year

Interesting preprint dissecting how DNA methylation and HUSH together repress human L1 retrotransposon transcription. Very surprising that HUSH (and H3K9me3) depletion in hNPCs has no impact on L1 transcription. I had a few thoughts about this work: 1/n

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Geoff Faulkner

@Faulkner_Lab

3 years

Study from Devine lab just published @genomeresearch . Reports >100K TE polymorphisms in nearly 58K individual genomes. Use of PacBio long reads to resolve internal sequences of ~650 full-length L1HS elements (in one study!). A wonderful resource. 👏👏

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Geoff Faulkner

@Faulkner_Lab

2 years

Had fun previewing @MolecularCell Article from @torbenheick showing convincingly that NEXT works with HUSH to limit retrotransposon RNA expression. Article here: Preview here: (Cartoon credit to Lizzy Haines and @eugeniaferreiro )

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Geoff Faulkner

@Faulkner_Lab

3 years

Preprint shows Cas9 to enrich @nanopore reads for human TEs in GM12878, very nice! -Might be used to profile TE family 5mC -Fair to note TE calling with ONT done by us (Ewing Mol Cell 2020) -Enrichment (L1HS vs L1PA2/L1PA3) may be tricky to calculate

Cas9 targeted enrichment of mobile elements using nanopore sequencing

Mobile element insertions (MEIs) are highly repetitive genomic sequences that contribute to inter- and intra-individual genetic variation and can lead to genetic disorders. Targeted and whole-genome...

www.biorxiv.org

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Geoff Faulkner

@Faulkner_Lab

4 years

This is an *outstanding* review, especially for anyone interested in measuring transposon expression with RNA-seq.

Sophie Lanciano

@sophie_lanciano

4 years

Excited to share with @retrogenomics @ircaninstitute our new review @NatureRevGenet on how to measure and interpret transposable elements expression

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Geoff Faulkner

@Faulkner_Lab

1 year

Very recent @genomeresearch functional genomics study of ERV enhancers in human trophoblast cells reveals new TF/ERV binding combinations (beyond e.g. STAT1/MER41) that appear to regulate genes essential to placenta development. 1/n

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Geoff Faulkner

@Faulkner_Lab

1 year

Welcome to the lab @charles_bell92 ! Charlie is interested in the transcriptional regulation of transposable elements, and is joining us after his PhD and first postdoc with @MAF_Dawson .

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Geoff Faulkner

@Faulkner_Lab

3 years

Paper in @NatureGenet showing L1 repression by MPP8 and a broader tumour suppressive function for L1 retrotransposition in AML is interesting but leaves me with some initial doubts about the endogenous L1HS analyses ... open to explanations 1/n

Silencing of LINE-1 retrotransposons is a selective dependency of myeloid leukemia

Nature Genetics - MPHOSPH8 loss inhibits acute myeloid leukemia (AML) development by reactivating LINE-1 retrotransposons. LINE-1 suppression is associated with therapy resistance and poor...

www.nature.com

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Geoff Faulkner

@Faulkner_Lab

10 months

Congrats to the decrypTEd team, short listed by @CancerGrand for the Retrotransposable elements challenge: The decrypTEd team is outstanding and the concept is very well thought out, would be great to see them succeed at the next stage.

Team decrypTEd

cancergrandchallenges.org

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Geoff Faulkner

@Faulkner_Lab

1 year

A couple of papers that would be worth referring to here. Firstly, this excellent review from @sophie_lanciano and @retrogenomics explains the objectives and pitfalls of RNA-seq analyses of TEs: 15/n

Measuring and interpreting transposable element expression - PubMed

Transposable elements (TEs) are insertional mutagens that contribute greatly to the plasticity of eukaryotic genomes, influencing the evolution and adaptation of species as well as physiology or...

pubmed.ncbi.nlm.nih.gov

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Geoff Faulkner

@Faulkner_Lab

4 years

Study published late 2019 in Nat Ecol Evol maps pachytene piRNA loci in humans. Fascinating that in humans (and mice: Aravin et al.) there are two waves of piRNA production. Early fetal piRNAs -> transposons, postnatal piRNAs -> non-transposons 1/n

Evolutionarily conserved pachytene piRNA loci are highly divergent among modern humans

Nature Ecology & Evolution - By mapping piRNA genes in juvenile and adult human testes, the authors show that although synteny is conserved with other mammals, sequences are diverging rapidly...

www.nature.com

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Geoff Faulkner

@Faulkner_Lab

3 months

I'll be speaking about our work on mobile DNA and escapee L1 retrotransposons at: JCBC (Uni Cambridge) 1pm April 12, Paul Lehner host IDRM (Uni Oxford) noon April 15, @RBerrens host ICTE conference (St Malo) 4pm April 21 I've been promised it'll be warm and sunny throughout :)

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Geoff Faulkner

@Faulkner_Lab

6 years

L1 retrotransposition in ovarian carcinoma paper just published @CellReports @Carreira_DrP #transposons . Main finding is that L1 mutations are heterogeneous in tumour cells and profile can change after chemo 1/n

L1 Retrotransposon Heterogeneity in Ovarian Tumor Cell Evolution

Acquired chemoresistance drives ovarian cancer mortality. Nguyen et al. show that L1 retrotransposons, a type of mobile genetic element, can escape silencing in ovarian tumor cells. They find a...

www.cell.com

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Geoff Faulkner

@Faulkner_Lab

5 months

Fascinating preprint from @JonasKoeppel et al uses prime editing to insert loxP sites into hundreds of human L1 copies, make a bit of a genetic mess, and then see how the genome evolves in vitro. Looks well done from a design and analysis standpoint too.

Randomizing the human genome by engineering recombination between repeat elements

While protein-coding genes are characterized increasingly well, 99% of the human genome is non-coding and poorly understood. This gap is due to a lack of tools for engineering variants that affect...

www.biorxiv.org

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Geoff Faulkner

@Faulkner_Lab

3 years

Preprint using HiC to resolve protein-DNA binding profiles of very young mammalian TE insertions is fantastic. Solves the "multi-map" problem quite well, using L1HS and MERVL for examples in human and mouse. 1/n @DarrenT243 @retrogenomics @BrancoLab

Locus-specific chromatin profiling of evolutionarily young transposable elements

Despite a vast expansion in the availability of epigenomic data, our knowledge of the chromatin landscape at interspersed repeats remains highly limited by difficulties in mapping short-read sequen...

www.biorxiv.org

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Geoff Faulkner

@Faulkner_Lab

3 years

@HardSciFiMovies @TheAlexKnapp @nanopore Reluctance because it was a deviation from what I want to work on. Obligatory because it's an area of potential public health concern and we (with crucial collaborator involvement) had the expertise and capacity to ask whether we could verify the original findings.

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Geoff Faulkner

@Faulkner_Lab

3 years

We did not overexpress the L1 RT, as HEK293T cells already provide a very friendly environment for L1 mobility, one that is unlikely to be encountered by the virus in vivo. Adding the L1 RT makes it even more artificial. I suppose we had better get that data out now. 6/6

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Geoff Faulkner

@Faulkner_Lab

4 years

Congratulations to my now former postdoc Sandy Richardson @SandyRtsn for her well deserved promotion to Academic Level C (Senior Research Fellow / Group Leader) by the University of Queensland. Going to do great things Sandy!

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Geoff Faulkner

@Faulkner_Lab

4 months

Preprint with @AnjanaRaoLab @SAMyers_lab dissects OGT-TET interaction. OGT mutation reduces mC, increases hmC, and increases retrotransposon expression. WGBS, ONT @nanopore and six-letter sequencing @biomodalhq methylomes from control and OGT iKO mESCs.

OGT prevents DNA demethylation and suppresses the expression of transposable elements in heteroch...

The O- GlcNAc transferase OGT interacts robustly with all three mammalian TET methylcytosine dioxygenases. We show here that deletion of the Ogt gene in mouse embryonic stem cells (mESC) results in a...

www.biorxiv.org

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Geoff Faulkner

@Faulkner_Lab

5 years

The best news I have heard in ages: senior lab postdoc Sandy Richardson @birdofparadox22 being awarded an @nhmrc EL1 grant. Sandy is the person whose ideas most often make me think "I wish I had thought of that, I wish I was that clever". Well deserved Sandy. #transposons

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Geoff Faulkner

@Faulkner_Lab

1 year

Pointing here to the response from Dr Liu which isn't as visible being further down in this thread. Thank you for providing this @ZunpengLiu . It clarifies some of the experimental design and presents heatmaps representing individual HERVK loci. As promised I expanded my analysis:

Zunpeng Liu

@ZunpengL

1 year

@Faulkner_Lab @CellCellPress We sincerely thank Dr. Faulkner @Faulkner_Lab for all these useful comments and discussions. Please see our full responses in the attachment. Figures can be found here: Thanks a lot!

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Geoff Faulkner

@Faulkner_Lab

2 years

Catching up on reading: this excellent study from @LabRowe really highlights how interconnected transposable element (TE) and gene regulatory mechanisms are: 1/n

A satellite DNA array barcodes chromosome 7 and regulates totipotency via ZFP819

An array of satellite DNA repeats on chromosome 7 acts as a switch enhancer to regulate Zscan4 genes and totipotency.

www.science.org

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Geoff Faulkner

@Faulkner_Lab

3 years

Article from my lab out at @GenomeBiology expanding the repertoire of pseudogene transcripts with PacBio long read sequencing. Some spectacular transcripts spanning TEs, pseudogenes and genes here! Esp credit to @SethCheetham @_adamewing @robinleetroskie

Long-read cDNA sequencing identifies functional pseudogenes in the human transcriptome - Genome...

Pseudogenes are gene copies presumed to mainly be functionless relics of evolution due to acquired deleterious mutations or transcriptional silencing. Using deep full-length PacBio cDNA sequencing of...

genomebiology.biomedcentral.com

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Geoff Faulkner

@Faulkner_Lab

3 years

Two @nature papers over the past couple of months have reported m6A regulation of transposable element (TE) expression in mESCs. These are really interesting studies but, to me at least, seem to make opposing findings regarding m6A applied to young L1s. 1/n

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Geoff Faulkner

@Faulkner_Lab

5 months

Some beautiful analysis in this paper, tells us a lot about L1 transcription and the regulatory relationships between L1 insertions and the loci they inhabit.

Sophie Lanciano

@sophie_lanciano

5 months

I'm so excited to announce that our story on LINE-1 DNA methylation has been published in @CellGenomics 🥳🥳 with @retrogenomics @DPratella @Orel_Doucet and all other authors. Enjoy the reading! See original thread below.

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Geoff Faulkner

@Faulkner_Lab

4 years

Peer review ramblings #1 : while there are many wonderful CNS papers, the quality of science done in the field-specific journals a tier or two below CNS is no lower than CNS. The divide between the claims made and the data in support is however often smaller.

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Geoff Faulkner

@Faulkner_Lab

3 years

Welcoming recently started NHMRC Emerging Leadership Fellow @tashjansz to the lab. Lots of fun mobile DNA and epigenomics projects to be had in the years to come!

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Geoff Faulkner

@Faulkner_Lab

2 years

Speaking of which, it's been about 3 years (~150 manuscripts) now of signing my referee reports and I can't say I've noticed any real drawbacks of doing so. Here are some things I've noticed: 1/n

Geoff Faulkner

@Faulkner_Lab

5 years

A few months back I started signing my journal referee reports. Various reasons for this. One positive I have discovered is that if I then supply a supportive but also critical review of a manuscript to a journal where it is rejected, the authors can address my critiques 1/n

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Geoff Faulkner

@Faulkner_Lab

4 years

Pre-print claiming reverse transcription of SARS-CoV-2 RNA does not show this. Where is the evidence for TPRT? Where is the insertion sequencing to find TSDs? qPCR to measure genomic integration of an RNA is about the lowest standard I could think of.

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Geoff Faulkner

@Faulkner_Lab

2 years

Last day of #AusEpi22 . Fun and well run conference in a great location. Lots of interesting work and good science chat too. Thanks @AEpiA (and saw whales migrating by at sunrise this morning).

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Geoff Faulkner

@Faulkner_Lab

5 years

A few months back I started signing my journal referee reports. Various reasons for this. One positive I have discovered is that if I then supply a supportive but also critical review of a manuscript to a journal where it is rejected, the authors can address my critiques 1/n

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Geoff Faulkner

@Faulkner_Lab

3 years

Paper in @genomeresearch evaluates how polymorphic Alu insertions modulate gene expression. V. interesting long-range Alu eQTLs found for breast cancer loci, including MYC, confirmed by CRISPR. Excellent work and congrats to the authors @KathleenHBurns

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Geoff Faulkner

@Faulkner_Lab

3 years

Lab glamping retreat to the rainforest. Lamington National Park. Fantastic place @tashjansz @SethCheetham @bodea_gabriela @robinleetroskie @YohaannJafrani @natenstuff1 @eugeniaferreiro

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Geoff Faulkner

@Faulkner_Lab

4 years

Paper out today @NatureGenet used CRISPR-Cas9 to delete DNMT and TET genes in human embryonic stem cells (hESCs) and then performed whole genome bisulfite sequencing (WGBS) to assess the impacts of these deletions upon the epigenome. Generally I thought this was well done. 1/n

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Geoff Faulkner

@Faulkner_Lab

1 year

Terrific work showing how sequence variation in IAP retrotransposons can cause them to escape TRIM28 silencing in embryonic and neural progenitor cells. Also complements what we and others have done recently on L1 retrotransposon escapees in somatic cells. Bravo!

RoweLab

@LabRowe

1 year

Excited this is out in @CellReports : Rocio Enriquez-Gasca & @DrPoppyGould shed light on how endogenous retroviruses gain beneficial roles in development & immunity, and why retrotransposons can jump in cancers, once epigenetic regulation is compromised:

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Geoff Faulkner

@Faulkner_Lab

1 year

Contributed to this Voices piece for the recent @MolecularCell special issue on the Central Dogma, and focused on the reverse transcriptase (RT) encoded by the L1 retrotransposon protein ORF2p. "What, if anything, does the ORF2p RT do in somatic cells?"

The complexity of transferring genetic information

The Central Dogma has been a useful conceptualization of the transfer of genetic information, and our understanding of the detailed mechanisms involved in that transfer continues to evolve. Here, we...

www.cell.com

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Geoff Faulkner

@Faulkner_Lab

2 years

@Nature study dissecting HUSH repression of L1 retrotransposons is my favourite mobile DNA paper of 2022. Tough decision ... this was the "one" for me due to design, execution and importance. And @seczynska answered questions convincingly. Great stuff!

Genome surveillance by HUSH-mediated silencing of intronless mobile elements

Nature - The human silencing hub (HUSH) complex uses introns to distinguish intronless foreign DNA from intron-containing host DNA and modifies chromatin to silence transcription of...

www.nature.com

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Geoff Faulkner

@Faulkner_Lab

1 year

Recent and very interesting @PNASNews study shows R2 retrotransposons help to maintain rDNA repeat copy number in the fly germline. R2 has told us a lot about retrotransposition (eg Eickbush's 1993 Cell paper on TPRT). I have some questions though: 1/n

The retrotransposon R2 maintains Drosophila ribosomal DNA repeats | PNAS

Ribosomal DNA (rDNA) loci contain hundreds of tandemly repeated copies of ribosomal RNA genes needed to support cellular viability. This repetitive...

www.pnas.org

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Geoff Faulkner

@Faulkner_Lab

3 years

To make it a bit clearer what I mean about the chr22 example from Zhang et al., I did a diagram of the ONT read to show its composition. Keep in mind that this is crucial to support the findings. It looks like some sort of artifact ... never seen an L1-mediated event like it.

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Geoff Faulkner

@Faulkner_Lab

1 year

The RNA-seq seems to have been via rRNA depletion, and featureCounts QC suggests ~35% of the reads align to introns. I (+others) have in the past noted the dramatic impact on transposable element (TE) quantitation these intronic reads can have. 9/n

Elevated L1 expression in ataxia telangiectasia likely explained by an RNA-seq batch effect

A recent study (Takahashi et al., Neuron , 2022) concluded LINE-1 (L1) retrotransposon activation drives cerebellar ataxia and neurodegeneration. This position was based on L1 upregulation in ataxia...

www.biorxiv.org

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Geoff Faulkner

@Faulkner_Lab

5 years

Pleased to join the @GenomeBiology Editorial Board. Highly visible place to publish relevant #transposon studies.

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Geoff Faulkner

@Faulkner_Lab

3 months

Finally got around to reading the newer mouse part of the Alu tail-loss paper () from @BoXia7 @ItaiYanai @JefBoeke . I know this story stirred up a lively debate but it all seems reasonably put to me and quite thoughtful when it comes to caveats ... 1/2

On the genetic basis of tail-loss evolution in humans and apes

Nature - An insertion of an Alu element into an intron of the TBXT gene is identified as a genetic mechanism of tail-loss evolution in humans and apes, with implications for human health today.

www.nature.com

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Geoff Faulkner

@Faulkner_Lab

4 years

Another reproducibility thread: the methylation data in the SPOCD1 KO O'Carroll lab Nature paper (Zoch et al.) are really impressive on closer examination, and if anything the paper understates the impact SPOCD1 and MIWI2 KO have on L1 methylation. 1/n

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Geoff Faulkner

@Faulkner_Lab

2 years

Congrats @Patricia_Grds and @RichardsonL1Lab ! This study tells us a lot about mouse L1 methylation dynamics during development. The @nanopore data in Fig 4 shows an incredible sawtooth 5mC profile on the mouse L1 5'UTR in mESCs. Interesting system of L1 truncation over time too.

Patricia Gerdes

@Patricia_Grds

2 years

🧬Excited to share that the 2nd story out of my PhD is now on bioRxiv!🧬We resolved locus-specific methylation dynamics of the monomeric mouse L1 promoter during development using bisulfite & nanopore sequencing! w/ @RichardsonL1Lab @Faulkner_Lab 👇 1/6

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Geoff Faulkner

@Faulkner_Lab

6 years

Excellent dCas9 epigenome editing method @ryanlisterlab @genomeresearch

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Geoff Faulkner

@Faulkner_Lab

4 months

Finally got time to look closely at preprint reporting a second HUSH complex, HUSH2, centred around the TASOR paralog TASOR2. Study does an excellent job of showing HUSH2 exists. Suggests there is competition between TASOR and TASOR2. A few thoughts: 1/n

Interplay between Two Paralogous Human Silencing Hub (HuSH) Complexes in Regulating LINE-1 Element...

The Human Silencing Hub (HuSH) complex is composed of TASOR, MPP8, and PPHLN1 subunits and serves as a conserved protein complex responsible for silencing transposable elements in vertebrate animals....

www.biorxiv.org

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Geoff Faulkner

@Faulkner_Lab

3 years

Discussed this @nature paper on HUSH at our journal club. Very positive consensus ... important findings supported by well designed science. I wonder though about the prior Wysocka lab result showing an intron was less important than codon optimisation 1/n

Genome surveillance by HUSH-mediated silencing of intronless mobile elements

Nature - The human silencing hub (HUSH) complex uses introns to distinguish intronless foreign DNA from intron-containing host DNA and modifies chromatin to silence transcription of...

www.nature.com

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Geoff Faulkner

@Faulkner_Lab

3 years

I'm looking to hire a full-time Research Assistant for my team at Mater. A broad molecular biology skill set is a must. Happy to answer questions about the role on DM or email. Please RT.

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Geoff Faulkner

@Faulkner_Lab

6 years

New review led by senior postdoc Gabriela Bodea just out in @RSocPublishing Open Biology. Idea was to write it for #neuroscience people interested in #transposon activity in brain. Focus on L1 in neurodegeneration and case studies. Hope it's useful.

Retrotransposon-induced mosaicism in the neural genome | Open Biology

Over the past decade, major discoveries in retrotransposon biology have depicted the neural genome as a dynamic structure during life. In particular, the retrotransposon LINE-1 (L1) has been shown to...

royalsocietypublishing.org

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Geoff Faulkner

@Faulkner_Lab

3 years

Paper published recently @NatureSMB focuses on nanopore methylome analyses of mouse transposable elements. Surprisingly, the FAST5 data files required to replicate the main findings, some of which are quite unexpected, are not available 1/n @CytoChromaC

Dnmt1 has de novo activity targeted to transposable elements

Nature Structural & Molecular Biology - The canonical DNA methylation maintenance enzyme Dnmt1 displays global de novo methylation activity with greater targeting towards IAP transposons, which...

www.nature.com

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Geoff Faulkner

@Faulkner_Lab

1 year

@eugeniaferreiro and I wrote a Spotlight "Endogenous retroviruses can propagate TDP-43 proteinopathy" for @TrendsNeuro on this terrific recent @NatureComms work from @joshdubnau Looking like an influential study for the field.

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