🚨 excited to share our latest preprint on bioRxiv, led by the soon-to-be Dr. Guy Kunzmann!
We tackle a striking case of conditional dependence on UFMylation, a UBL modification pathway whose contributions to cell fitness have been a bit of a "black box." 🧵
The cover art, inspired by the classic Pink Floyd cover art from "The Dark Side of the Moon", depicts a white noise protein oscillation being filtered by a yeast expressing a specific synthetic circuit design into more precise, single-color waveforms. This visual echoes the noise-guided design strategies associated with Bolshakov et al.
Congratulations to my student Dennis Bolshakov and his coauthors @weix.us, Tommy, and @born2raisecell.bsky.social on making the cover of ACS Synthetic Biology! A great paper and an awesome cover 🥳 pubs.acs.org/doi/10.1021/...
Huge congratulations to my student Rohith Rajasekaran @born2raisecell.bsky.social (now a postdoc in Kole Roybal's lab at UCSF) on being selected for a Weintraub award! Super proud of you and all the work you've done!
Some excellent preLights to end 2025 🎆
The latest was written by Zhang-He Goh @goh-zhanghe.bsky.social, discussing an enzymatic method for tryptophan-specific bromination described in a recent #preprint from the lab of @amyweeks.bsky.social.
#preLight ⬇️
prelights.biologists.com/highlights/e...
Great work by recently minted PhD Haley Bridge and recent BS Chase Radziej! We are grateful to the NIH for supporting this work. Public investment in fundamental science fuels innovation and is worth defending.
We found that 4V produced higher conversion and had expanded sequence scope compared to RebH. We took advantage of this newly revealed activity to combine enzymatic bromination with Suzuki-Miyaura cross-coupling to enable late-stage chemoenzymatic functionalization of unmodified bioactive peptides.
The observation of peptide activity in RebH motivated us to examine the RebH variant 4V, which was engineered by @jclewislab.bsky.social to accommodate larger substrates 👇onlinelibrary.wiley.com/doi/abs/10.1002/anie.201...
New preprint! We found that the flavin-dependent halogenase RebH catalyzes sequence-tolerant Trp bromination in peptides 🧪www.biorxiv.org/content/10.64898/2025.12...
New in ACS SynBio: led by Dennis Bolshakov, we used the awesome power of yeast to define how expression levels, noise, and sequence program the dynamics of synthetic protein waves, allowing us to genetically encode new cellular timescales stable over generations!
pubs.acs.org/doi/full/10....
Thrilled to share our work on the 🔥 single-celled predator Podophrya collini, which rewires its cell morphology to hunt more efficiently. Huge thanks to our amazing team—Amy, Lauren, Omaya, Marine, Mari, and especially Scott—for making this shine! ✨
How do cells adapt morphology to function? In a 🔥 preprint by @zjmaggiexu.bsky.social , with @dudinlab.bsky.social and @amyweeks.bsky.social , we identify a self-organizing single-cell morphology circuit that optimizes the feeding trap structure of the suctorian P. collini. 🧵 tinyurl.com/4k8nv926
A beautiful example of how spatiotemporal dynamics can enable multiplexed measurements.
Excited to share our new preprint, which was years in the making! chemrxiv.org/engage/chemr...
New reactions are typically developed by trial and error. How can we speed up this process? Read on to learn how we used DNA scaffolding to perform >500,000 parallel reactions on attomole scale.
1/n
A handmade poster that says "We are all in this together" with a DNA double helix in the center.
Congratulations to first author Kasia Radziwon and co-authors Laura Campbell, Lauren Mazurkiewicz, Sopo Jalalshvili, Izabelle Eppinger, and Aanika Parikh! We are grateful to the NIH for supporting this work. Public investment in fundamental science fuels innovation and is worth defending.
A crystal structure of the OspF homolog SpvC bound to a substrate peptide. Plots of % sites beta-eliminated for pThr and pSer with several OspF variants.
Leveraging the throughput of our approach, we took a deep dive into the molecular basis of OspF specificity. We identified enzyme residues in the L12 loop that influence OspF’s specificity for pThr vs. pSer and were able to shift this specificity through protein engineering
OspF is a pThr lyase from Shigella flexneri that targets MAPKs in innate immune signaling. We profiled OspF activity on PhosPropels and found that its catalytic domain has an intrinsic preference for the the MAPK activation loop motif pThr-X-pTyr.
We also found that the catalytic domain of the pThr lyase OspF (a functionally and mechanistically distinct phosphoeraser from Shigella flexneri) has and intrinsic preference for the pThr-Xaa-pTyr motif found in Erk and p38 MAP kinase activation loops that does not depend on its MAPK docking motif
The Legionella pneumophila phosphatase WipB targets the lysosomal nutrient sensing machinery. WipB disfavors substrates with Pro at +1 and phosphosites flanked by acidic residues.
We applied our approach to define sequence motifs for 8 phosphoerasers spanning diverse species, folds, and enzymatic mechanisms. Example: The Legionella pneumophila phosphatase WipB uses multiple selectivity filters, disfavoring substrates with Pro at +1 and phosphosites flanked by acidic residues
Workflow for PhosPropel-based profiling of phosphoerasers. Cells are lysed, protein is digested, and phosphopeptides are enriched to generated a phosphoproteome-derived peptide library (PhosPropel). The PhosPropel can then be treated with a phosphoeraser enzyme and analyzed using LC-MS/MS to profile enzyme specificity.
We developed an LC-MS/MS-based in vitro assay for dephosphorylation of human phosphoproteome-derived peptide libraries (PhosPropels). We use statistical comparison of phosphopeptide sequence features in enzyme-treated samples vs. controls for deep specificity profiling of phosphoeraser enzymes.
Phosphorylation is regulated by the activities of writers and erasers. Lots of progress has been made in defining kinase sequence specificity (e.g., www.nature.com/articles/s41...), but there are fewer approaches for studying phosphoeraser specificity
Position-specific frequency matrices can be used to calculate z-scores comparing enzyme-treated and control samples. The z-scores are plotted as heatmaps that represent an enzyme specificity profile.
New preprint: we developed a method that uses phosphoproteome-derived peptide libraries (PhosPropels) for deep specificity profiling of phosphatases and phospholyases www.biorxiv.org/content/10.1...
OspF is a pThr lyase from Shigella flexneri that dampens innate immune signaling. We treated PhosPropels with OspF and found that this enzyme has intrinsic specificity for the pThr-X-pTyr motif of MAPK activation loops independent of an N-terminal MAPK docking motif.
We also found that the catalytic domain of the pThr lyase OspF (a functionally and mechanistically distinct phosphoeraser from Shigella flexneri) has and intrinsic preference for the pThr-Xaa-pTyr motif found in Erk and p38 MAP kinase activation loops that does not depend on its MAPK docking motif
WipB is a Ser/Thr phosphatase from Legionella pneumophila that targets lysosomal nutrient sensing machinery. PhosPropel analysis revealed that WipB disfavors substrates with Pro at +1 and phosphosites flanked by acidic residues.
We applied our approach to define sequence motifs for 8 phosphoerasers spanning diverse species, folds, and enzymatic mechanisms. Example: The Legionella pneumophila phosphatase WipB uses multiple selectivity filters, disfavoring substrates with Pro at +1 and phosphosites flanked by acidic residues
Workflow for phosphoeraser specificity profiling. Cells are lysed, protein is digested, phosphopeptides are enriched, the phosphopeptide library is treated with an eraser enzyme, and phosphosites are analyzed by LC-MS/MS
We developed an LC-MS/MS-based assay for dephosphorylation of human phosphoproteome-derived peptide libraries (PhosPropels). We use statistical comparison of phosphopeptide sequence features in enzyme-treated samples vs. controls for deep specificity profiling of phosphoerasers.
Phosphorylation is regulated by the activities of writers and erasers. Lots of progress has been made in defining kinase sequence specificity (e.g., www.nature.com/articles/s41...), but there are fewer approaches for studying phosphoeraser specificity
Check out our new manuscript on parallel LC separations! Super cool how the very high scan rates of modern MS systems coupled with DIA can allow us to run several samples at the same time with little loss in depth. Congrats to Noah and the team. #JASMS pubs.acs.org/doi/10.1021/...
Bravo to Clara Frazier, Debashrito Deb
@thepeptidetailor.bsky.social and coauthors Will Leiter @wleiter1999.bsky.social and Umasankar Mondal!
Excited to share our latest: we engineered the reactivity of a bacterial E1-like enzyme for ATP-driven modification of C termini. Our tool mimics the logic of peptide bond formation in biology for precision modification of proteins in vitro. 🧪https://rdcu.be/ewN7C
Great success at the Ono Pharma Foundation Symposium in Boston! Highlights include inspiring talks by Xiao Wang @amyweeks.bsky.social Robert Spitale @stevenbanik.bsky.social @michael-erb.bsky.social Matthew Shoulders Michelle Arkin and a keynote from Chuan He. Posters fueled inspired exchange.
Debashrito Deb holding up his poster award at the 2025 Bioorganic GRC
Congrats to Weeks lab graduate student Debashrito Deb @thepeptidetailor.bsky.social, who won a poster prize at the Bioorganic GRC last week! Thanks to conference chairs @doc-jlmeier.bsky.social and Denise Field who knocked it out of the park with a memorable and inspiring meeting this year!
Despite ~20 years in/around #chembio research, I went to my first Bioorganic GRC this week. This community is amazing and so supportive. I feel energized (and tired, lol) and find myself rooting for the next generation of chemical biologists. Sooooo much awesome science - We can’t/won’t be stopped!
