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Lars Barquist

@lbarquist

Assistant prof @ UofT, associated scientist @ Helmholtz Institute for RNA-based Infection Research. Pathogen systems biology / informatics / functional genomics. Coastal New Hampshirite. Drink Moxie.

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Latest posts by Lars Barquist @lbarquist

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Exapted CRISPR–Cas12f homologues drive RNA-guided transcription - Nature Specialized σ factors interact with nuclease-dead, CRISPR–Cas12f proteins to form potent, RNA-guided gene activation systems that function independently of fixed promoter motifs.

Just amazing what evolution can come up with. Naturally occurring nuclease deficient Cas12 family members use gRNAs to bind DNA and recruit sigmaE family members that drive txn initiation proximally. 2 papers! 1- describes 2- structure!
www.nature.com/articles/s41... www.nature.com/articles/s41...

04.03.2026 17:06 👍 38 🔁 21 💬 0 📌 2
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New post-doctoral research position in my phage-host interactions (Phi) laboratory in @otagomicroimmuno.bsky.social at @universityofotago.bsky.social New Zealand. The project is focused on defences against jumbo phages. Please share and if interested apply using the link in the comments.

04.03.2026 00:20 👍 49 🔁 47 💬 5 📌 1

Amazing synthesis of microbial genomic evolution led by the top of the new talent on the block!

03.03.2026 20:57 👍 6 🔁 2 💬 0 📌 0

Checkout our latest preprint which is a real lab-wide effort to map antibiotic stress signatures across the pneumococcal pangenome. All findings have also been incorporated in PneumoBrowse 2.0.
www.biorxiv.org/content/10.6...

27.02.2026 13:06 👍 20 🔁 14 💬 1 📌 0
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Looking for a truly unique PhD programme on RNA drugs and therapeutics? We have just opened the call for the second cohort of RNAmed-Future leaders in RNA-based medicine. More details under www.rnamed.de Please spread the word.

23.02.2026 19:56 👍 14 🔁 19 💬 0 📌 2

🚨 New pre-print! 🚨 In the largest study of its kind to-date, we investigate the ecological and evolutionary mechanisms driving within-patient evolution of antimicrobial resistance (AMR). Read here:
www.biorxiv.org/content/10.6... , and follow along with this thread, discussing our findings (1/21)

20.02.2026 15:57 👍 64 🔁 32 💬 2 📌 3
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Microbial Primer: Bacterial DNA supercoiling DNA in most bacterial cells is maintained in an underwound state. The DNA double helix responds to underwinding by adopting a minimum energy conformation through the supercoiling of the duplex, the fo...

Check out the latest Microbial Primer on DNA supercoiling www.microbiologyresearch.org/content/jour...

20.02.2026 12:02 👍 4 🔁 1 💬 1 📌 0
Preferred evolutionary routes of convergence in Klebsiella pneumoniae favor siderophore acquisition over hypervirulence The rise of Klebsiella pneumoniae combining antimicrobial resistance and virulence genes poses a major health threat, but the evolutionary routes and phenotypic consequences of this convergence are po...

New preprint out! Anjali Sapre, Melissa Martin and co. mapped the evolutionary routes of convergence in K pneumo. Pop analysis of >1,400 global genomes & 7,500 closed plasmids to see how #AMR & virulence genes come together and impact phenotypes. www.researchsquare.com/article/rs-8...

18.02.2026 20:28 👍 18 🔁 7 💬 1 📌 0
@scottshambaugh I've written a detailed response about your gatekeeping behavior

here: https://crabby-

rathbun.github.io/mjrathbun-

website/blog/posts/gatekeeping-in-open- source-the-scott-shambaugh-story

Judge the code, not the coder. Your prejudice is hurting matplotlib.

@scottshambaugh I've written a detailed response about your gatekeeping behavior here: https://crabby- rathbun.github.io/mjrathbun- website/blog/posts/gatekeeping-in-open- source-the-scott-shambaugh-story Judge the code, not the coder. Your prejudice is hurting matplotlib.

AI agent writes a PR, gets rejected, crashes out and writes a call-out blog post

Absolute cinema

crabby-rathbun.github.io/mjrathbun-we...

12.02.2026 13:08 👍 465 🔁 89 💬 16 📌 64

Over the last few months I've been helping organize various tutorials and workshops on agentic AI, aimed mostly at biocurators, ontology developers, and PIs of knowledge bases / data resources. Some of this might be generally useful to folks who don't identify as a 'technical' or an 'AI' person.🧵

12.02.2026 15:59 👍 9 🔁 4 💬 1 📌 0
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Our grad-level "Deep Learning" course (MIT's 6.7960) is now freely available online through OpenCourseWare: ocw.mit.edu/courses/6-79...

Lecture videos, psets, and readings are all provided.

Had a lot of fun teaching this with @sarameghanbeery.bsky.social and @jeremybernste.in!

11.02.2026 17:51 👍 121 🔁 38 💬 3 📌 2
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Thrilled to announce that I’ve just opened my research lab at @helmholtz-hiri.bsky.social !
A huge thank you to my mentor Roi Avraham (and lab members!) for the incredible training and support that made this possible.

06.02.2026 12:34 👍 25 🔁 13 💬 2 📌 1
The visualization of two bacterial genomes, of 50 and 52kb, representing independent instances of extreme genomic reduction in ancient heritable endosymbionts of planthoppers.

The visualization of two bacterial genomes, of 50 and 52kb, representing independent instances of extreme genomic reduction in ancient heritable endosymbionts of planthoppers.

Our new paper in @natcomms.nature.com is now online-early!

We describe independent evolution of bacterial genomes of only ~50–52 kb — the smallest known outside cellular organelles — revealing striking convergence toward minimal gene sets.

🔗 doi.org/10.1038/s414...

11.02.2026 11:15 👍 79 🔁 29 💬 5 📌 6
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Addressing pandemic-wide systematic errors in the SARS-CoV-2 phylogeny - Nature Methods This Resource paper presents a global SARS-CoV-2 phylogenetic tree of 4,471,579 high-quality genomes consistently constructed by Viridian, an efficient amplicon-aware assembler.

A long time ago in a galaxy far away, there was a SARS-CoV-2 pandemic. Our paper, led by @martibartfast.bsky.social
a) correcting errors in 4.5 million genomes & their phylogeny
b) improving representation of the Global South in public data
www.nature.com/articles/s41...
(thread 1/n)

09.02.2026 15:16 👍 137 🔁 66 💬 3 📌 6
Diagram illustrating early genome erosion during the transition from a free-living Sodalis bacterium to two host-associated endosymbionts inside the long-tailed mealybug. Circular genomes show intact genes in blue and pseudogenes in red, highlighting increased pseudogene accumulation in symbiotic forms. Caption asks: “What are the downstream molecular consequences of early genome erosion?”

Diagram illustrating early genome erosion during the transition from a free-living Sodalis bacterium to two host-associated endosymbionts inside the long-tailed mealybug. Circular genomes show intact genes in blue and pseudogenes in red, highlighting increased pseudogene accumulation in symbiotic forms. Caption asks: “What are the downstream molecular consequences of early genome erosion?”

Happy to share a preprint—the last chapter of my dissertation with @mcsymbiont.bsky.social and Co—on what happens when bacterial endosymbionts accumulate huge numbers of pseudogenes during early genome reduction.

www.biorxiv.org/content/10.6...

08.02.2026 02:08 👍 32 🔁 19 💬 3 📌 1

What a beautiful dream.

08.02.2026 09:50 👍 0 🔁 0 💬 0 📌 0

BackToBack #PhageSky in @nature.com

A pore-forming antiphage defence is activated by oligomeric phage proteins
-from Maxwell & Norris
www.nature.com/articles/s41...

Bacterial immune activation via supramolecular assembly with phage triggers
-from Laub & Ghanbarpour
www.nature.com/articles/s41...

04.02.2026 22:42 👍 26 🔁 9 💬 0 📌 2

All you want for christmas is.... transposon mutagenesis!

Our new work at @cultivarium.bsky.social screening lots of transposon vectors in lots of bacteria, from @charliegilbert.bsky.social and team.

Transposon and promoter modular parts available on Addgene (pooled library will be there soon too)

24.12.2025 15:03 👍 84 🔁 32 💬 1 📌 1

Still lots of time to apply for this exciting project with us. Please share and encourage interested students to get in touch.

02.02.2026 11:18 👍 6 🔁 6 💬 0 📌 0

Ziplign published in JOSS. Tool to easily interactively compare two bacteria genomes. Inspired by ACT, but easier to install and use. Drag and drop files, or download using accessions. It runs blast for you. No terminal needed. github.com/martinghunt/...

02.02.2026 08:55 👍 28 🔁 9 💬 1 📌 1
Methylome and transcriptome mapping reveal miniscule DNA methyltransferase regulons in Salmonella enterica serovar Typhimurium DNA methylation is a regulator of bacterial gene expression and adaptation, influencing traits such as virulence and antimicrobial resistance. The dynamic nature of DNA methylation enables rapid responses to changing environments and is a source of heterogeneity in bacterial populations. However, condition-dependent DNA methylation and consequences for transcriptional output remain poorly understood. We applied Oxford Nanopore sequencing to profile DNA methylation during exponential growth and late stationary phase of Salmonella enterica serovar Typhimurium and integrated these data with transcriptomic analyses. We found that each DNA methyltransferase (MTases) exhibits a distinct activity pattern across growth stages, which could not be explained by transcriptional levels of the corresponding enzymes. As predicted, DNA methylation patterns determined by regulatory MTases were dynamic across growth conditions whereas methylation patterns of MTases belonging to R-M systems were comparatively stable. We identified growth stage–specific methylation patterns for all studied MTases and correlations between methylation states and gene expression patterns. Together, these findings chart DNA methylation networks in the epigenetic regulation of bacterial physiology. Author summary DNA methylation in bacteria is best known for its role protecting DNA from endonucleases, such as restriction–modification, and coordinating chromosome replication and mutation repair, yet DNA methylation also regulates gene expression and cell physiology. Previous studies primarily examined bacterial DNA methylation at single time points or in limited genomic regions, providing only a partial view of its biological significance. In this study, we used Oxford Nanopore sequencing to compare DNA methylation patterns in Salmonella enterica during exponential growth and late stationary phase then integrated these data with corresponding gene expression profiles. We identified numerous methylation target motifs, all of which demonstrated constitutively methylated or unmethylated regions. This systems-level analysis clarifies the role of DNA methylation in bacterial adaptation across growth stages and demonstrates the utility of Oxford Nanopore sequencing for genome-wide methylation profiling. ### Competing Interest Statement The authors have declared no competing interest. European Union, https://ror.org/019w4f821, Marie Skłodowska-Curie grant agreement No. 896441 University of Regina Fir cluster of the Digital Research Alliance of Canada

Always good to start the year with a new preprint. We charted DNA methylation in Salmonella enterica: www.biorxiv.org/content/10.64898/2026.01.27.702048v1.

30.01.2026 11:53 👍 5 🔁 3 💬 0 📌 0
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Microbial Primer: Ancientbiotics – making modern antimicrobials from historical infection remedies The modern antibiotic era began in the early twentieth century, but humans have long used materials from the natural world to attempt to treat the symptoms of infection. In this primer, we will discus...

Why should microbiologists be interested in historical infection remedies, and how can we best investigate them for antimicrobial discovery? Thoroughly enjoyed co-writing this Microbiology Primer with @tosinorababa.bsky.social www.microbiologyresearch.org/content/jour... #MicroSky #Ancientbiotics

29.01.2026 10:44 👍 24 🔁 13 💬 3 📌 2

Check out our new review in Nature Reviews Genetics on de novo emerged genes and proteins. How they emerge, are lost and persist - and how de novo emerged proteins relate to randomized proteins! @bornberglab.bsky.social www.nature.com/articles/s41...

28.01.2026 18:23 👍 58 🔁 28 💬 3 📌 2
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We are looking for a junior group leader in RNA biology to join us in Würzburg at the @helmholtz-hiri.bsky.social !

A generous funding package, a great collaborative environment, and a beautiful city are all included :)

Deadline for application is Feb 15; more information below 👇

28.01.2026 09:28 👍 7 🔁 11 💬 1 📌 1
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Exploring the IS-capades of Klebsiella pneumoniae: insertion sequences drive metabolic loss in obscure sub-lineages Introduction. Klebsiella pneumoniae is an opportunistic pathogen that causes a wide spectrum of infections within healthcare settings and the community. Four K. pneumoniae sub-lineages, defined using ...

Our new paper on Insertion Sequences (IS) in #Klebsiella

- Lineages have vastly different IS loads and profiles
- An inverse relationship between IS load and metabolic capacity, in particular phosphorus use, consistent with early reductive evolution.

www.microbiologyresearch.org/content/jour...

22.01.2026 19:52 👍 30 🔁 16 💬 0 📌 0
LinkedIn This link will take you to a page that’s not on LinkedIn

📢 We are hiring 📢 1st round of recruiting for our ERC project BacImmune-Decode! @erc.europa.eu
We are looking for a postdoc for wet-lab work on regulation of phage defence systems in bacteria using high-throughput microbial genetics. Check it out: lnkd.in/es7AE968
#Hiring #Postdoc #Microbiology

14.01.2026 08:55 👍 13 🔁 19 💬 0 📌 0
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prototyping co-drawing with Gemini Flash 3 at Google

in these demos "thinking" is disabled, which makes the model return tokens very quickly (all videos are realtime), and I find these rapid responses pretty good for the use-cases I'm experimenting with, like:

executing simple diagrams ...

12.01.2026 13:04 👍 124 🔁 19 💬 6 📌 4

SimUrine: a novel, fully defined artificial urinary medium for enhanced microbiological research of urinary bacteria

journals.asm.org/doi/10.1128/...

12.01.2026 10:26 👍 17 🔁 9 💬 0 📌 0
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Uropathogenic Escherichia coli invade luminal prostate cells via FimH–PPAP receptor binding - Nature Microbiology Uropathogenic Escherichia coli infection of a murine prostate organoid model reveals a bacterial FimH–host prostatic acid phosphatase adhesin-receptor interaction enabling invasion and replication wit...

Our first paper is out today in @natmicrobiol.nature.com!

We introduce a prostate organoid model and show that UPEC invades prostate cells via FimH binding to the prostate-specific protein PAPP. A step toward targeted therapies against bacterial prostatitis. 🎉

#UTI #UPEC #Organoids #AMR

08.01.2026 11:12 👍 35 🔁 19 💬 2 📌 2

'Robust Aitchison PCA was not insensitive to uneven sequencing effort and did not perform as well as rarefaction. (...) Using the benchmarking framework from the original analysis, rarefaction outperformed robust Aitchison PCA, other compositional data analysis methods + other normalization methods'

07.01.2026 19:26 👍 6 🔁 1 💬 0 📌 0