Craig M. Crews

A vision of chromosome organization Cryogenic electron tomography of condensed chromatin enables multiscale analysis of its structure

@science.org 🧬🔬 A vision of #chromosome organization | Science www.science.org/doi/10.1126/...
@vram142.bsky.social et al.

A BRET biosensor for measuring uncompetitive engagement of PRMT5 complexes in cells - Nature Communications This study presents a BRET biosensor that measures how anticancer drugs cooperatively engage PRMT5 complexes in cells, revealing how cellular metabolites such as SAM and MTA enhance drug action and en...

New in @natcomms.nature.com: a live-cell BRET biosensor to study how PRMT5 inhibitors engage their target in a tumour-context cellular environment (1/4)

Open access paper: doi.org/10.1038/s414...

•Reviews how mitochondrial protein import maintains cellular and organelle homeostasis.
•Summarizes the main stress response pathways (ISR, UPRam, UPRmt, mitophagy) triggered by import dysfunction.
www.sciencedirect.com/science/arti...

Precipitation-first synthesis and deep profiling of a 1200-member acrylamide library for covalent drug discovery Screening libraries of low molecular weight (LMW) compounds are foundational in early-stage drug discovery. However, the parallel synthesis of milligram-scale large libraries – especially for covalent inhibitors – remains constrained by resource-intensive purification protocols, high solvent consumption, and

Interesting paper by the group of Alexander Dömling in Green Chemistry. They used an Ugi four-component reaction followed by product precipitation for the efficient synthesis and purification of a >1200-member acrylamide library.

pubs.rsc.org/en/cont...
#CovalentInhibitors #ChemSky #ChemBio

YouTube video by CellMorphoJSero Introduction to CellProfiler - by a biologist, for biologists!

If you or your trainees are just getting started with image analysis of cells & are #CellProfiler -curious, here is a fairly thorough walk-through demo I did recently. Loading files, extracting metadata (fun with Regex!), identifying objects, measuring, filtering, QC, exporting:
youtu.be/fO5nJdhj_7I

Dated gene duplications elucidate the evolutionary assembly of eukaryotes - Nature Analysis of eukaryotic gene sequences using a relaxed molecular clock methodology indicate that eukaryotes emerged 3.0–2.25 billion years ago as a result of mitochondrial endosymbiosis with complex ar...

Eukaryogenesis was a billion year spree, but the acquisition of mitochondria happened when the party was winding down www.nature.com/articles/s41...

Bentley-DeSousa, Roczniak-Ferguson and @shawnferguson.bsky.social reveal converging roles of STING and #lysosome damage in activating LRRK2 at #lysosomes via interactions between LRRK2 & GABARAP rupress.org/jcb/article/...

📕 From The Year In Cell Biology: rupress.org/jcb/collecti...
#CellBio2025

Primate embryo model leaps across developmental boundaries A stem-cell-based monkey embryo model that self-organizes into a comprehensive body plan could lead the way to more-sophisticated models of early human development.

A stem-cell-based monkey embryo model that self-organizes into a comprehensive body plan could lead the way to more-sophisticated models of early human development

go.nature.com/48yxsG6

Linker Modification Enables Control of Key Functional Group Orientation in Macrocycles Macrocycles are promising drug modalities that can enable unique ways of conformational preorganization, but how even minor modifications to a macrocyclic scaffold influence the conformational preorga...

Linker Modification Enables Control of Key Functional Group Orientation in Macrocycles | Journal of Medicinal Chemistry pubs.acs.org/doi/full/10....

A stepwise decoding mechanism for heat sensing in plants connects lipid remodeling to a nuclear signaling cascade A complete hierarchical thermo-decoding mechanism in plants connects cell membrane lipid remodeling during heat stress to the downstream signaling cascade in the nucleus. Field trials demonstrate the potential application of this mechanism in customized heat-tolerant crop design in rice.

Now online! A stepwise decoding mechanism for heat sensing in plants connects lipid remodeling to a nuclear signaling cascade

Unleashing the Power of Potassium 2-Ethylhexanoate as a Mild and Soluble Base for Pd-Catalyzed C–N Cross-Coupling The formation of C–N bonds by Pd-catalyzed cross-coupling is one of the most widely practiced reactions in chemical synthesis. Typical reaction conditions involve either a strong base, which limits the scope of substrates, or an insoluble, inorganic base, which complicates running reactions on a large scale. Reaction conditions for C–N couplings with a base that is both mild and soluble are needed. We report the discovery of a combination of a phosphorinane ligand (L147) and a soluble carboxylate base, potassium 2-ethylhexanoate (K-2-EH), which leads to the coupling of a wide range of base-sensitive coupling partners. To explore the enhanced substrate scope of the reaction with this base and catalyst, we evaluated the scope using representative reactants selected from published partners, using chemical descriptors and clustering to ensure their chemical diversity. These results show that the combination of this phosphorinane ligand and K-2-EH can couple primary aliphatic amines, amides, sulfonamides, and heteroaromatic nucleophiles as well as acidic secondary nitrogen nucleophiles, such as arylamines, heteroarylamines, and amides, with a range of electrophiles. A side-by-side comparison to form selected coupling products in the presence of a range of previously reported bases and ligands showed that the products that decomposed under standard reaction conditions were stable with K-2-EH as a base. Finally, models of quantitative structure–reactivity relationships, trained on ligand screening data, were developed to help reveal the structural features that engender reactivity.

Excited to share our new method for Pd-catalyzed C–N cross-coupling, now published in @jacs.acspublications.org!

This method utilizes an inexpensive, mild, and soluble base suitable for small & large scales with excellent functional group tolerance across chemical space.

doi.org/10.1021/jacs...

news.yale.edu/2025/12/01/p...

Specialized signaling centers direct cell fate and spatial organization in a mesodermal organoid model Stem cell–derived mesodermal organoids reveal how signaling centers guide cell fate and tissue organization.

🎉 Our deconstructed, stem-cell–based approach to studying signaling centers and limb-development cell types is out! 🥳 So nice to see it in its final form after the preprint— and huge thanks to the community for all the enthusiasm and interest since then!
www.science.org/doi/10.1126/...

Induced ubiquitination bypasses canonical ERAD to drive ER protein degradation Heterobifunctional proteolysis-targeting chimeras (PROTACs) have emerged as a powerful strategy to degrade disease-relevant proteins, enabling targeting of previously "undruggable" proteins. Current d...

New preprint out! We show that PROTAC-induced ubiquitination can bypass canonical ERAD to degrade ER membrane proteins. Wonderful collaboration w/ @dannomura.bsky.social and huge credit to grad student superstar Sydney Tomlinson!
www.biorxiv.org/content/10.1...

Design, Synthesis, and Structural Evolution of Pseudo‐Natural Product IDO1 Inhibitors and Degraders The combination of bicyclic monoterpene- and pyrrolidine-alkaloid fragments yields novel pseudo-natural products. Biological characterization revealed that these iDegs are inhibitors and degraders of...

Design, Synthesis, and Structural Evolution of Pseudo-Natural Product IDO1 Inhibitors and Degraders - Published by the Waldmann Group in @angewandtechemie.bsky.social

onlinelibrary.wiley.com/doi/10.1002/...

The epitranscriptome formed by the growing number of modifications occurring within mRNA transcripts.

We have been mapping mRNA modifications for over a decade.

=> Characterizing their functions -- especially on translation -- is a research frontier.

How do new centromeres evolve while staying compatible with the division machinery?

Discover it in our new Nature paper! We show centromeres transition gradually via a mix of drift, selection, and sex, reaching new states that still work with the kinetochore.

👉 doi.org/10.1038/s41586-025-09779-1

A new plant oxygen sensing mechanism, based on methylation of histone H3

What a fantastically interesting story this is, congratulations to the authors!

ZAK activation at the collided ribosome - Nature The kinase ZAK is activated at collided ribosomes to mediate the ribotoxic stress response.

Check out our latest work on how collided ribosomes activate the MAP3K ZAK! 💫

www.nature.com/articles/s41...

A fun collaboration with @beckmannlab.bsky.social @doubleshuang.bsky.social

AlphaFlex: Ensembles of the human proteome representing disordered regions www.biorxiv.org/cont...

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#proteomics #prot-preprint

Morphogen Math: A Model of Axolotl Limb Growth during Regeneration In a new publication led by the Friedrich group at PoL and the Sandoval-Guzmán group at CRTD, scientists propose a model of morphogen scaling during limb regeneration in axolotls.

🎉Paper alert! How do #axolotls regrow their limbs to match their body size? A new publication by PoL @friedrich-group.bsky.social along with @tatianasg.bsky.social @crtd-tud.bsky.social shows that opposing morphogen gradients scaling with animal size are key.

Curious? Read our news: tud.link/z6tj5y

ZAK activation at the collided ribosome - Nature The kinase ZAK is activated at collided ribosomes to mediate the ribotoxic stress response.

Nature research paper: ZAK activation at the collided ribosome

go.nature.com/4a9cika

Proteome-wide model for human disease genetics Nature Genetics - popEVE is a proteome-wide deep generative model to identify and predict pathogenicity of missense mutations causing genetic disorders.

popEVE is out in Nature Genetics! 🎉
We built a proteome-wide model that combines cross-species and human population variation to rank missense variants by disease severity and help diagnose rare genetic disorders.
rdcu.be/eRu7K

The second part of our (with @origichals.bsky.social and El Hadji) two-part review on non-covalent SUMO interactions is now published, focussing on SUMO-interacting motifs (SIMs), but discussing also other confirmed or potential SUMO-interacting elements.

AlphaFold Protein Structure Database 2025: a redesigned interface and updated structural coverage Abstract. The AlphaFold Protein Structure Database (AFDB; https://alphafold.ebi.ac.uk), developed by EMBL–EBI and Google DeepMind, provides open access to

From Sameer Velankar & colleagues in @narjournal.bsky.social #NARDatabaseIssue | #AlphaFold #Protein #Structure #Database 2025: a redesigned interface and updated structural coverage | #Bioinformatics #Proteomics #OpenScience #AFDB 🧪🔓 CC/ @ebi.embl.org
⬇️
academic.oup.com/nar/advance-...

Circular DNA has a ticket to ride chromosomes Nature - How circular extrachromosomal DNA is inherited during cell division is a puzzle. Key sequences enabling this DNA to journey with chromosomes have been identified.

How circular extrachromosomal DNA is inherited during cell division has been a puzzle

go.nature.com/441YKU7

AlphaFold Protein Structure Database 2025: a redesigned interface and updated structural coverage academic.oup.com/nar...

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#proteomics #prot-paper

Proteome-wide in silico screening for human protein-protein interactions Protein-protein interactions (PPIs) drive virtually all biological processes, yet most PPIs have not been identified and even more remain structurally unresolved. We developed a two-step computational...

Thrilled to share that the final piece of my PhD work is now on bioRxiv! biorxiv.org/content/10.1... With support from @nvidia and the @NSF, we used AlphaFold to screen 1.6M+ protein pairs, revealing thousands of potential novel PPIs. All data can be viewed at predictomes.org/hp

How does messenger RNA (mRNA) get out of the nucleus to become a protein? Eukaryotic mRNA is packaged, exported, and then translated in the cytoplasm. But how do these steps work? And what are open questions? Check out our new review for our take: www.annualreviews.org/content/jour... (1/3)

I tried the updated Gemini image generator on scientific related image prompts that have failed in the past and I am really impressed by the quality of the outputs. The first is drawing a diagram for a pocket prediction algorithm using Voronoi diagram, Delaunay triangulation and alpha shapes