Liana Merk

Great new story from Sophie Helaine and Molly Sargen!

www.helainelab.com

This was a really fun and interesting Molecule of the Month to do! Check out the article to see even more elaborate RNA-only structures.

🎉 New year, NEW PREPRINT!

Bacteria exhibit astonishing genetic diversity, but where do new genes come from?

My best friend Arya Kaul (/labmate in the @baym lab) investigates how advantageous deletions can spawn new genes - "deletion-born fusions." 🧵:

🚀New preprint from our lab!
I am very excited to finally share what has been the main focus of my PhD for the past almost 3 years! It is about viral dark matter and a powerful tool we built to shed light on it. 🧬💡
Continue reading (🧵)

This is it!!! This is the work I never want to stop hearing about. Kepler’s creativity and curiosity really shine through in this paper. Give it a read and enjoy 😎

Super excited that the bulk of my PhD work is now preprinted! Here we used whole-community competition, or coalescence, experiments to quantify selection acting on genetically diverged strains within larger communities. (1/n)
www.biorxiv.org/content/10.1...

Been working on a really strange retron bacterial immune system, here's the preprint: www.biorxiv.org/content/10.1...
Type VI retrons are unlike any other. Phage infection triggers reverse transcription of a DNA fragment that activates translation of a toxin to kill the infected cell.

Antiviral reverse transcriptases reveal the evolutionary origin of telomerase Defense-associated reverse transcriptases (DRTs) employ diverse and distinctive mechanisms of cDNA synthesis to protect bacteria against viral infection. However, much of DRT family diversity remains ...

1/10 Genome maintenance by telomerase is a fundamental process in nearly all eukaryotes. But where does it come from?

Today, we report the discovery of telomerase homologs in a family of antiviral RTs, revealing an unexpected evolutionary origin in bacteria.
www.biorxiv.org/content/10.1...

RNA Structure beyond Canonical Base Pairs Guided by Evolution - Harvard University - Department of Molecular & Cellular Biology In addition to messenger RNA (mRNA) that provide the code for proteins, there are other RNAs that exert their function just as RNA, usually referred to as non-coding […]

RNA Structure beyond Canonical Base Pairs Guided by Evolution 🧪🧬 #AcademicSky #higherEd
www.mcb.harvard.edu/department/n... @rivaselenarivas.bsky.social @rachellegaudet.bsky.social @cryptogenomicon.bsky.social @dulaclab.bsky.social @neurovenki.bsky.social @naoshigeuchida.bsky.social

You’ve heard of ubiquitination, meet deazaguanylation: Doug Wassarman in our lab discovered phage defense pathways have co-opted Q nucleobase biosynthetic enzymes to catalyze a new form of protein conjugation chemistry @science.org

www.science.org/doi/10.1126/...

Genomic resistance in historical clinical isolates increased in frequency and mobility after the age of antibiotics Antibiotic resistance is frequently observed shortly after the clinical introduction of an antibiotic. Whether and how frequently that resistance occurred before the introduction is harder to determin...

What was antibiotic resistance like before we ever used antibiotics? How did we change what antibiotic resistance genes looked like over 100 years?

Our paper looking at resistance genes from a century of NCTC historical isolates now out in mGen:
www.microbiologyresearch.org/content/jour...

Disco lights

Phage DisCo! Our targeted phage discovery method in press today: journals.asm.org/doi/10.1128/...

Perfectly timed with our four summer undergrad's first successful phage hunt... disco lights in the lab to mark the occasion 🕺

My father worked in a tire factory in Appalachia. Friends and family in the military. Used to vote Republican. Got into college on a diversity program for the underprivileged. Ended up a Harvard professor. And now my funding is terminated because we're trying to stick it to the elites.

The war on science in the US is already having an effect on private sector research like AlphaFold. Bears repeating but the private sector builds on top of things created by academic research for the public good. This hurts everyone.

Thanks Kep same to you🫡

(7/7) We’d love to hear your thoughts, and if you are at the RNA conference in San Diego this week, I am presenting this work at P2-353 in the second poster session!

(6/7) We highlight a few stories: evidence for retroposition into phage-specific loci, unique CapR domains not reported in group II intron-encoded homing endonucleases, and the presence of a group II intron in an annotated Inovirus, the first group II intron noted in a single stranded DNA organism.

(5/7) We use three lines of evidence along with Infernal hits. (1) The presence of full-length intronless homologs of genes the group II’s are inserted in. (2) Identification of pseudoknotted tertiary base-pairing not modeled by Infernal. (3) Similarity of intron-encoded ORFs to known group II ORFs.

(4/7) Recent accelerations in Infernal, a profile SCFG-based search and alignment tool from our lab, allow us to find these large RNAs across large genomic and metagenomic datasets.

(3/7) We wondered if they haven’t been widely identified in phage because they are challenging to find — they have low primary sequence similarity. Luckily, their splicing mechanism dictates strong conservation in parts of their secondary structure.

Group II intron mechanism

(2/7) Group II introns are self-splicing RNAs and the speculative ancestor of our own nuclear spliceosomal introns. They are widely known in bacterial, archaeal, and eukaryotic orgenallar genomes, but considered absent in phage.

Prevalence of Group II Introns in Phage Genomes Although bacteriophage genomes are under strong selective pressure for high coding density, they are still frequently invaded by mobile genetic elements (MGEs). Group II introns are MGEs that reduce h...

(1/7) Very excited to share my first PhD preprint on the interactions of two of my favorite mobile genetic elements: phages and group II introns!

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

Tick-borne flavivirus exoribonuclease-resistant RNAs contain a double loop structure - Nature Communications Many flaviviruses generate specialized non-coding RNAs that resist degradation by host exonucleases, promoting viral infection. Here, the authors characterize an RNA element in Powassan virus, highlig...

Final grad paper is officially out! Grateful for the incredible team and all the support along the way!
www.nature.com/articles/s41...

Zero-shot design of drug-binding proteins via neural selection-expansion Computational design of molecular recognition remains challenging despite advances in deep learning. The design of proteins that bind to small molecules has been particularly difficult because it requ...

Super excited to share a new preprint from our lab on design of small-molecule binding proteins using neural networks! The paper has a bit of everything. A new graph neural network, new design algorithms, and experimental validation. www.biorxiv.org/content/10.1...
🧵🧪

Congratulations!!

Llamas, dolphins and measles? Oh my!

So thankful this story is finally breaking containment from my time in the Manguso Lab at the Broad. Using pieces from viruses and llamas we engineered selective cell specific viral like particles with reduced immunogenicity for in vivo gene delivery

rnahub.og
A webserver to generate RNA alignments with secondary structure assessment

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

Intracellular competition shapes plasmid population dynamics Conflicts between levels of biological organization are central to evolution, from populations of multicellular organisms to selfish genetic elements in microbes. Plasmids are extrachromosomal, self-r...

I'm so happy that I can finally share the results of my first postdoc paper with @baym.lol!!! Turns out plasmids are an amazing system to study multi-scale evolution and we can track within-cell and between-cell dynamics!
(1/n) www.biorxiv.org/content/earl...