A Research Briefing on our MitoPerturb-Seq paper just came online @natsmb.nature.com too: www.nature.com/articles/s41.... Hopefully even more accessible than the manuscript! 😉

MitoPerturb-Seq identifies gene-specific single-cell responses to mitochondrial DNA depletion and heteroplasmy - Nature Structural & Molecular Biology Burr and Auckland et. al develop MitoPerturb-Seq, which combines single-cell screening with multiomics to link nuclear genes to mitochondrial DNA (mtDNA) dynamics. They unveil core regulators of mtDNA...

Really pleased to see this out @natsmb.nature.com: www.nature.com/articles/s41.... MitoPerturb-Seq combines #singlecell #CRISPR screening with whole-cell Multiome, to identify nuclear modifiers of mtDNA dynamics. @mitocamb.bsky.social @mrc-mbu.bsky.social @prudentlab.bsky.social and Stephen Burr

📢 We are inviting you to the second session of the 2026 @cambridgeflyclub.bsky.social talks.

Fantastic to join the #EdinburghScienceFestival with our lab’s Stitch and Fly workshop!
We had a highly interactive, fully booked session discussing our research alongside fruit fly-inspired stitching!
Huge thanks to the PhD students in our lab and SBS public engagement team.
#Drosophila #Genetics

Wonderful and honoured to write a perspective with @prudentlab.bsky.social @mrc-mbu.bsky.social on such an intriguing and cool observation of beautiful mitochondrial biology! Amazing work on how pearling allows mitochondrial genome organisation by @jclandoni.bsky.social @sulianamanley.bsky.social!

GitHub - JvdAlab/mitoPerturb-Seq: Analysis scripts for "MitoPerturb-Seq identifies common and gene-specific single-cell responses to mitochondrial DNA depletion and heteroplasmy" Analysis scripts for "MitoPerturb-Seq identifies common and gene-specific single-cell responses to mitochondrial DNA depletion and heteroplasmy" - JvdAlab/mitoPerturb-Seq

All scripts available on Github: github.com/JvdAlab/mito..., with thanks to the bioinformatics expertise of Kate Auckland and Abhilesh Dhawanjewar. @mbu-postdocs.bsky.social

Doing all this at single-cell resolution allowed high-throughput, and was essential to capture the mosaic nature of mtDNA. Hopefully #MitoPerturb-Seq will lead to discovery of novel mtDNA maintenance and quality control genes, and solve cell-type specific vulnerabilities to #mitochondrialdisease.

Simultaneous RNA- and mtDNA-sequencing also allowed analysis of mtDNA replication throughout the cell-cycle, which we find to be fully relaxed. However, depletion of mtDNA results in cell-cycle slowing across all cell-cycle stages, and not just the G1-S checkpoint.

Using #DamID-seq, we found that only ~1/3 of the differentially-expressed genes was directly bound by the canonical stress-response transcription factor Atf4, with many more factors identified by #SCENIC for future exploration.

Perturbation of Tfam, Opa1 or Polg caused mtDNA depletion, which increased heteroplasmy variance. Maybe not so surprising, but simultaneous RNA-seq then allowed us to study the single-cell transcriptional response to mtDNA depletion, which was much stronger to Opa1, than to Tfam or Polg gRNAs.

We build on CROP-seq #CRISPR screening, whole-cell ATAC-seq and 10xGenomics Multiome protocols from @leifludwig.bsky.social @caleblareau.bsky.social, and mtDNA and gRNA enrichment approaches, to study how nuclear gene perturbations impact mtDNA heteroplasmy and copy number in mouse fibroblasts.

MitoPerturb-Seq identifies gene-specific single-cell responses to mitochondrial DNA depletion and heteroplasmy - Nature Structural & Molecular Biology Burr and Auckland et. al develop MitoPerturb-Seq, which combines single-cell screening with multiomics to link nuclear genes to mitochondrial DNA (mtDNA) dynamics. They unveil core regulators of mtDNA...

Really pleased to see this out @natsmb.nature.com: www.nature.com/articles/s41.... MitoPerturb-Seq combines #singlecell #CRISPR screening with whole-cell Multiome, to identify nuclear modifiers of mtDNA dynamics. @mitocamb.bsky.social @mrc-mbu.bsky.social @prudentlab.bsky.social and Stephen Burr

@jellevda.bsky.social @ritahorvath.bsky.social @lilyfoundation.bsky.social @londonmito.bsky.social @mitonewcastle.bsky.social

We probably shouldn’t have favourites amongst projects in the lab, but this one was mine. I’m so pleased we can finally share it:

Our work is now out in Nature Communications:
🔗 nature.com/articles/s41467-025-67692-7

Closes 12/01/2026. A great team and a great centre to be a part of!

@camneurodept.bsky.social @taylorlabncl.bsky.social @jellevda.bsky.social @ritahorvath.bsky.social @robpitceathly.bsky.social

Charting the phenotypic landscape of mitochondrial diseases through a systematic evaluation of pathogenic mitochondrial DNA and nuclear gene variants Primary mitochondrial diseases (PMD) arise from variants in the mitochondrial or nuclear genomes. Phenotype-based recognition of specific PMD genotypes remains difficult, prolonging the diagnostic ody...

www.gimjournal.org/article/S109...
I am very proud of this new paper! Congratulations to Thiloka and the team of young researchers! 👍

Excited to share our first bioinformatics contribution! 🎉 Led by Niek Wit in collaboration with the van den Ameele lab @jellevda.bsky.social , we developed DamMapper damid-seq.readthedocs.io/en/latest/, a workflow for DamID-seq analysis, to map SET1B and HIF-1 chromatin occupancy. rdcu.be/eK2TS

Delighted that Ziqi Dong's PhD paper is out for all to read! Hypoxia is fundamental to normal development, and fascinating! Thanks to all of our co-authors including @jamesnathanlab.bsky.social @jellevda.bsky.social authors.elsevier.com/sd/article/S...

High heteroplasmy decreases mitochondrial ubiquitination

Bluesky, I am pleased to present to you the main product of postdoc work, published in @science.org ☝️

As it turns out, the very quality control mechanism that can remove mutant mtDNA copies is the one that maintains high mutant burden, or heteroplasmy levels

This is amazing news!! @camneurodept.bsky.social @mrc-mbu.bsky.social @jellevda.bsky.social @ritahorvath.bsky.social @mito-news.bsky.social

📢 We are hiring a Senior Research Associate in Bioinformatics & Statistical genetics @cam.ac.uk @mrc-mbu.bsky.social @camneurodept.bsky.social @jellevda.bsky.social It's a great time to join this dynamic and world leading team working on #mitochondria Closes 28/8/25

www.cam.ac.uk/jobs/senior-...

Welcome to the new serie of Cambridge Fly Club meetings. We organise several events every year to foster collaboration and maintain a positive dynamic between Drosophila groups in Cambridge.

Thanks to @lilyfoundation.bsky.social for taking these snaps of the centre leads and team members! Together we hope to do great things over the next 5 years of the LifeArc Centre! #mito @ucl-qs-cnmd.bsky.social @taylorlabncl.bsky.social @ritahorvath.bsky.social @jellevda.bsky.social

Plaque showing that we are proudly part of the LifeArc Centre for Rare Mitochondrial Diseases, with funding from MDUK

We spent a great afternoon at the House of Lords for the launch of the @lifearc.bsky.social Centre for #Rare #Mitochondrial Diseases, supported by @mdukcharity.bsky.social The event centre hosted staff, dignitaries, patients, MPs & those involved in rare disease policy & research. We even unveiled…

It was a great day and a fantastic #PPIE workshop!! @lifearc.bsky.social @ritahorvath.bsky.social @jellevda.bsky.social @robpitceathly.bsky.social @taylorlabncl.bsky.social @dwong47.bsky.social @mitogene.bsky.social @mrc-mbu.bsky.social @mitonewcastle.bsky.social @uclqsion.bsky.social

🚨 Join us for the @faseborg.bsky.social
Meeting on Mechanisms of Mitochondrial DNA Mutation and Repair, June 1 - 5, 2025 | Nashville, Tennessee. 📅 Abstract submission & Early Registration close on April 20, 2025! Don't miss out: events.faseb.org/event/mitoch... Please re-post!

2x CRA posts extended until end of April. So you have another chance to work with #mito disease patients as part of the @lifearc.bsky.social centre for #rare #mito diseases! See links below to apply!
@eastgenomics.bsky.social @camneuro.bsky.social @cuhnhs.bsky.social

Data collected with the new sequencing platform HyDrop v2 is shown. First, a schematic overview of the bead batches of the microfluidic beads is followed by a tSNE and a barplot showing the costs in comparison to 10x Genomics. Then, a track of mouse data (cortex) is shown together with nucleotide contribution scores in the FIRE enhancer in microglia. Here, the HyDrop and 10x based models show the same contributions. On the right, the Drosophila embryo collection is explained; in the paper HyDrop v2 and 10x data are compared to sciATAC data. Then, a nucleotide contribution score is also shown, whereas HyDrop v2 and 10x models show the same contribution, just as in mouse.

Our new preprint is out! We optimized our open-source platform, HyDrop (v2), for scATAC sequencing and generated new atlases for the mouse cortex and Drosophila embryo with 607k cells. Now, we can train sequence-to-function models on data generated with HyDrop v2!
www.biorxiv.org/content/10.1...

We are hiring #bioinformaticians. One post to work on the new @lifearc.bsky.social centre for rare #mitochondrial diseases, and one is a joint project @mrc-mbu.bsky.social with Prof Patrick Chinnery & @mitogene.bsky.social
Apply here:
www.jobs.cam.ac.uk/job/50861/
www.jobs.cam.ac.uk/job/50860/

Exited to share our latest preprint! mRNA-LNPs are efficiently delivered to healthy livers, but what about liver tumours? Our postdoc @laura-leighton.bsky.social found liver tumours efficiently take up mRNA, enabling next generation mRNA-LNP cancer therapeutics.

www.biorxiv.org/content/10.1...