Very proud of this work and all the efforts from my team and collaborators on this! You can now use DGRs for in vivo targeted hypermutagenesis in E. coli. We also included some early proof of concept in Yeast thanks to @seth-shipman.bsky.social !
Posts by Alex Solivan
Excited to share our new findings in @science.org on how the DRT3 bacterial defense system uses a reverse transcriptase that builds DNA repeats without a nucleic acid template. Microbes never cease to amaze!
www.science.org/doi/10.1126/...
Finally published. Many thanks to a wonderful collaborative team and scientific platforms!!! And thanks to editors and reviewers for enthusiasm and a great review.
www.nature.com/articles/s41...
🔈Paper out! We turned the most fascinating phage host-switch mechanism, diversity-generating retroelements, into a programmable mutagenesis tool, DGRec. You can perform targeted hypermutation of any 50-200bp sequence directly in vivo in E. coli www.nature.com/articles/s41...
I feel like this paper just changed my brain chemistry. Absolute game changer and I can’t wait to see what comes next!
We are delighted that our article "Munc13-4–STX7 inhibitors impair endosomal TLR activation and systemic inflammation" is now published online in Nature Chemical Biology. Please see our discovery of ENDOtollins here: rdcu.be/fbU78
Munc13-4–STX7 inhibitors impair endosomal TLR activation and systemic inflammation @natchembio.nature.com
www.nature.com/articles/s41... @scripps.edu
Bacteria have been fighting off viruses using a huge arsenal of molecular weaponry that scientists did not know about — until now. Researchers have identified proteins that could lead to virus-fighting drugs and technologies.
go.nature.com/4dqQnXI
Excited to see our work out in Science today! Using machine learning to identify prokaryotic immune systems www.science.org/doi/10.1126/...
Mets fan since day 1 but I’ve enjoyed watching the Giants (and briefly the As) since moving to the Bay
And if you have not been accepted, understand that this is a VERY weird time for grad admissions. Lack of acceptance may not be due to YOU, but due to uncontrollable factors at the university. Keep trying in the future.
CBASS is a cyclic nucleotide-based antiviral system in bacteria that is related to cGAS-STING signaling in animals. One of the big questions is how CBASS is activated during phage infection? We made some progress on this during my final year in the Kranzusch lab.
www.biorxiv.org/content/10.6...
A jumbo cyanophage encodes the most complete ribosomal protein set in the known virosphere www.biorxiv.org/content/10.1...
Out now! In collaboration with Leifu Chang, we uncover the molecular and structural underpinnings of CRISPR-Cas12f-like RNA-guided transcription systems!
Links to the published articles:
tinyurl.com/55kpavet
tinyurl.com/sk6djwx3
Previous thread for the preprint:
bsky.app/profile/did:...
Science update from my postdoc Peiyuan Chai - his work “glycoRNA complexed with heparan sulfate regulates VEGF-A signaling” is now published @nature.com uncovering a new layer or glycoRNA-regulation of growth factor mediated control physiological processes rdcu.be/e1bBX
New #glycotime discovery from @raflynn5.bsky.social’s lab @bostonchildrens.bsky.social @harvard.edu, cell surface glycoRNA-RBP complexes organized by heparan sulfate PG nanoclusters that modulate VEGF signaling
www.nature.com/articles/s41...
The full biosynthetic pathway is still unknown as far as I’m aware but probably involves some bonker RIPP enzymes. Another reminder that Nature is the best chemist around
They’re also super weird to categorize as molecules. Technically you can end up with two isomers depending on if the Trp-sulfoxide ring is “up” or “down” relative to the rest of the ring but they’re also not true atropisomers as you can’t heat one to interconvert into the other
Dreams really do come true 🎊 I'm extremely excited to be joining the University of Vermont this fall as a Tenure-track Assistant Professor in Chemistry!
A research team has found multiple lineages of archaea that have fully repurposed the TAG stop codon to encode the noncanonical amino acid pyrrolysine. cen.acs.org/biological-c... #chemsky 🧪
Today, I'm grateful that Alanna Schepartz is visiting Tufts. Alanna's leadership of @cgemcci.bsky.social has led to impressive advances in genetic code expansion, including recently published work pushing encoding beyond alpha-amino acids.
#ChemSky #ChemChat
www.nature.com/articles/s41...
I’m a fan of this paper from Gillingham that looks at some macrocyclic DELs as a more standard pick (onlinelibrary.wiley.com/doi/full/10....) and this work on a protein-templated DEL system might be an interesting curveball!
www.nature.com/articles/s41...
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/...
“Hypervalent iodide giveth and hypervalent iodide taketh away”
Well it’s chemistry of course. The reason why organic chemists historically make p-tosylates rather than the simpler benzenesulfonates is that p-tosyl chloride is a cheap byproduct from saccharin synthesis. The ortho isomer is used for saccharin. #chemsky 🧪
>1700 examples???
Finally out in Nature Chem Bio:
SNAP-tag2 for faster and brighter protein labeling
www.nature.com/articles/s41...
Thank you Steffi and Veselin.
How do you turn a carbonyl into sulfur?
In this work, Zining from our lab developed a carbonyl-to-sulfur swap enabled by a rationally designed N′-alkyl-hydrazonamide (NAHA) reagent that promotes double C-C bond activation.
www.science.org/doi/10.1126/...
Seems a good time to post the “Top types of med chem papers” #ChemSky