Marcin J. Suskiewicz

Based on the outcomes of our project, we have created a pamphlet designed to be used in research laboratories. #researchintegrity #researchclimate #researchmisconduct

I feel attacked

- Model bacterial genomes as sequences of proteins
- predict protein-protein interactions, operon structure, and protein function
- infer phenotypic traits
- design synthetic genomes with desired properties

@macwiatrak.bsky.social @mariabrbic.bsky.social
@andresfloto.bsky.social

Beyond monomeric structures, accurate prediction of protein-protein interactions is crucial for understanding protein function. MSA Pairformer substantially outperforms all other methods in predicting residue-residue interactions at hetero-oligomeric interfaces

Scaling down protein language modeling with MSA Pairformer Recent efforts in protein language modeling have focused on scaling single-sequence models and their training data, requiring vast compute resources that limit accessibility. Although models that use ...

Excited to share work with
Zhidian Zhang, @milot.bsky.social, @martinsteinegger.bsky.social, and @sokrypton.org
biorxiv.org/content/10.1...
TLDR: We introduce MSA Pairformer, a 111M parameter protein language model that challenges the scaling paradigm in self-supervised protein language modeling🧵

The big difference is in the pairing. The MMseqs2 server pairs sequences based on species, while our old HHblits MSAs were paired based on genome proximity (number of genes apart). Working w/ @milot.bsky.social and @martinsteinegger.bsky.social we implemented the proximity filtering in server (3/4)

Unexpectedly, @jurgjn.bsky.social found that running Alphafold3 predictions for protein interactions can yield ipTM scores that are more predictive of true interactions when run in pools of proteins instead of pairwise predictions. Presumably, this reflects some sort of "competition effect".

Escherichia coli with a 57-codon genetic code The near-universal genetic code uses 64 codons to encode the 20 canonical amino acids and protein synthesis. Here we designed and generated Escherichia coli with a 4 Mb synthetic genome in which we re...

Escherichia coli with a 57-codon genetic code | Science www.science.org/doi/10.1126/...

Post-Translational Modifications Remodel Proteome-Wide Ligandability Post-translational modifications (PTMs) vastly expand the diversity of human proteome, dynamically reshaping protein activity, interactions, and localization in response to environmental, pharmacologi...

Excited to share a new preprint from the lab. We show that PTMs like phosphorylation & glycosylation dynamically reshape proteome-wide ligandability in cells, including proteins like KRAS. Great collaboration with the Huang Lab, @forlilab.bsky.social and BMS. www.biorxiv.org/content/10.1...

The histone core domain evolves at single-residue resolution to directly orchestrate transcription Nucleosomes are thought to be structural barriers to transcription, establishing a restrictive ground state that must be destabilized for gene express…

Happy to share our new paper out today in @cp-cellreports.bsky.social in collaboration with @tobiaswarnecke.bsky.social @akihisaosakabe.bsky.social about how evolution can do big things with small changes. www.sciencedirect.com/science/arti...

[Resources]

#AlphaFold protein and PPI prediction databases

1️⃣ Predictomes (genome maintenance & H2A/H2b) predictomes.org

2️⃣ Flypredictome www.flyrnai.org/tools/fly_pr...

3️⃣ Human interactome prodata.swmed.edu/humanPPI

4️⃣ BFVD (viral proteins) bfvd.steineggerlab.workers.dev

1/2

Metagenomic selections reveal diverse antiphage defenses in human and environmental microbiomes Rodríguez-Rodríguez et al. use functional metagenomics to identify hundreds of sequences from diverse environmental bacteria that block phage infection when expressed in E. coli. Their discoveries inc...

The diversity of bacterial defence systems against phages (restriction endonuclease, #CRISPR, phage protein
sensing system (RexAB), cyclic oligonucleotide-based (CBASS), ADP ribosylation (DARTG)) is simply fascinating, and we continue to discover new ones !!!

www.cell.com/cell-host-mi...

Sub-3 Å resolution protein structure determination by single-particle cryo-EM at 100 keV Cryoelectron microscopy (cryo-EM) has transformed structural biology by providing high-resolution insights into biological macromolecules. We report s…

Now out in Structure: Paper on high-resolution #cryoEM using the 100 kV Tundra cryo-TEM by Dimple Karia, Adrian Koh, @abhaykot.bsky.social, @lingboyu.bsky.social, @landerlab.bsky.social and many others. Happy to have contributed to this effort. Check it out:
www.sciencedirect.com/science/arti...

Physicists disagree wildly on what quantum mechanics says about reality, Nature survey shows First major attempt to chart researchers’ views finds interpretations in conflict.

I'm thrilled to see Lizzie's piece on quantum interpretations finally appear in @nature.com. This is a big survey and gives a good snapshot of the state of play. And lots of great quotes in here.
www.nature.com/articles/d41...

DirectContacts2: A network of direct physical protein interactions derived from high-throughput mass spectrometry experiments Cellular function is driven by the activity proteins in stable complexes. Protein complex assembly depends on the direct physical association of component proteins. Advances in macromolecular structur...

We are excited to share our preprint describing DirectContacts2! Here we develop a machine learning model to discriminate between direct and indirect protein interactions. We use our model to construct a highly accurate wiring diagram of the human cell.

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

“Revolutionary Science Comes from Unexpected Angles”

Thoughts from our own Tom Rapoport on the role of basic science in curing disease. magazine.hms.harvard.edu/articles/rev...

Recurrent acquisition of nuclease-protease pairs in antiviral immunity Antiviral immune systems diversify by integrating new genes into existing pathways, creating new mechanisms of viral resistance. We identified genes encoding a predicted nuclease paired with a trypsin...

Excited to finally share this work!
We noticed a pair of genes - a nuclease and a protease - shuffles between antiviral systems. We show how proteolysis activates the nuclease, triggering defense in known and unknown immune contexts.
tinyurl.com/2uwwy4ty

DNA mutagenesis driven by transcription factor competition with mismatch repair Competition between transcription factors and mismatch repair machinery drives localized hypermutation at regulatory elements, with implications for cancer and genome evolution.

Now online! DNA mutagenesis driven by transcription factor competition with mismatch repair

Manipulation of the nucleotide pool in human, bacterial and plant immunity - Nature Reviews Immunology Modification of the nucleotide pool is emerging as key to innate immunity in animals, plants and bacteria. This Review explains how immune pathways conserved from bacteria to humans manipulate the nuc...

NEW Review from @soreklab.bsky.social @dinahoch.bsky.social explains how immune pathways manipulate the availability of nucleotides, chemically modify nucleotides to generate immune signalling molecules, and produce altered nucleotides that poison viral replication
#immunosky #microsky #phagesky

Twenty years ago, a breakthrough at the ICR helped change how we treat cancers caused by BRCA-mutant genes – using a concept called synthetic lethality to target their underlying DNA repair weaknesses.

Thrilled to see our study on how kinesin-2 motors are switched on and off published in @natsmb.nature.com ⚛️

➡️ www.nature.com/articles/s41...

Congrats to all authors from me and Anthony 🎉 @dunnschool.bsky.social Check out this animation made by talented PhD student @matthew-batisio.bsky.social 😆

Excellent nanomolar peptide design success rates with BindCraft!

Kiwa is a membrane-embedded defense supercomplex activated at phage attachment sites Zhang, Todeschini, and Wu et al. show that the bacterial defense system Kiwa senses phage attachment at the membrane and assembles a transmembrane complex that halts infection by blocking phage DNA re...

Thrilled to see our Kiwa story out today! A membrane-associated supercomplex that senses infection and blocks replication and transcription.

www.cell.com/cell/fulltex...

Huge congratulations to Yi and Zhiying for bringing it home, to Thomas for starting us off, and to all the collaborators.

Changes to the 2026 and 2027 Work Programmes With the launch of the competitions for grants under ERC Work Programme 2026 in July of this year, several changes to the submission of applications and the evaluation of proposals will apply. The mai...

Planning to apply for #research #funding from the ERC?

From the next application rounds, expect changes to the:

• proposal structure
• evaluation process
• extra funding you can request
• eligibility for Starting & Consolidator #Grants (from 2027)

More 👇 europa.eu/!RPHWvv

And it's out!

I'm thrilled to share our new paper (Adriaenssens et al., Nat Cell Biol 2025).

This paper describes a new mechanism for the initiation of autophagosome biogenesis.

We found that this WIPI-ATG13-driven pathway is preferentially used by a group of transmembrane autophagy receptors.

@aithyra.bsky.social Opening Symposium "AI for Life Science" with Nobel Laureate Frances Arnold as keynote speaker in addition to an outstanding line up of speakers on a variety of topics across biological scales and data modalities.

Registration is now open at cemm.at/aithyra-symp...

Congratulations and looking forward to further exciting science with your signature style!

Gas Phase Separation of Modified Peptides for Activity-Based Protein Profiling Profiling the reactivity of the proteome with amino-acid level resolution requires the identification and quantification of reacted peptides in the presence of abundant unmodified peptides. Affinity-b...

An inspiring paper by the group of Jacob Geri in Analytical Chemistry. They present a method for residue-specific #chemoproteomics without the need for an enrichment step. To achieve this, they developed reagents that shift the ion mobility for gas phase separation. pubs.acs.org/doi/full/10....

ChimeraX daily builds can predict binding affinity of small molecules using Boltz 2 on your Mac, Windows or Linux computer. www.rbvi.ucsf.edu/chimerax/dat...