First inhibitor of a bacterial two-partner secretion system. Two-partner secretion system transporter proteins (TpsB) are widely conserved across Gram-negative pathogens. TpsB family proteins secrete exoprotein virulence factors that perform a myriad of functions such as adhesion and immune modulation. Despite their incredible importance in bacterial infectious disease, TpsB inhibitors have not yet been discovered. Here, we describe a potent inhibitor of FhaC, a TpsB protein produced by Bordetella spp . FhaC secretes the exoprotein FhaB that is essential for the establishment of whooping cough. We designed a peptide called P1 that we predicted would prevent substrate binding and lock FhaC in a secretion-inactive state. Simulations and biochemical assays supported our hypothesis and identified interactions important for P1 binding to FhaC. Strikingly, we observed that the peptide strongly inhibited FhaB secretion from clinical isolates and broadly reduced correlates of virulence. Together, this work provides a strong case for further development of a novel class of anti-TpsB anti-virulence compounds. ### Competing Interest Statement The authors have declared no competing interest. National Institute of Allergy and Infectious Diseases, R21AI180112

💊 We are excited to share our preprint that describes an inhibitor of the widespread and highly conserved Two-Partner Secretion (TPS) system that is critical for Gram-negative pathogens to export a multitude of diverse virulence factors.

(1/6)

www.biorxiv.org/content/10.6...

Black text on white background. Screenshot of ARC’s Network Message regarding delays to grant announcements because of new security arrangements.

⁉️The ARC has delayed outcomes of ALL grants 1–4 months & increased scheduled outcome windows from 2 weeks to 3 months!

This reverses 4 years of progress in providing greater certainty & ability to plan for researchers, their families & unis.

Their excuse? Security checks under new ARC legislation👇

The latest research from our team is out in Cell @cp-cell.bsky.social! We used #cryo-EM, #imaging, #BRET, and #biosensors targeted to the lysosome to understand how the KICSTOR-GATOR1 complex turns off #mTORC1 in response to low levels of amino acids.

Happy to finally share the amazing results of our long-term collaboration with Karin Reinisch’s lab on how bridge lipid-transfer proteins (BLTPs) cooperate with partner proteins to orchestrate lipid delivery. A quick thread (1/7)
www.biorxiv.org/content/10.6...

Yes, I reviewed Future fellowships a few years ago before I was eligible to apply myself.

Congrats Martin, well deserved!

Long-read on [NiFe]-hydrogenase Huc in @laborjournal.bsky.social (German language, RP with a proper image 🤗) www.laborjournal.de/rubric/journ...

I'm deeply honoured & grateful to have been awarded the #CSLCentenaryFellowship at the #AAHMS dinner last week

Many thanks to my mentors & colleagues for their support

Congratulations to my Fellow winner @rhyswg.bsky.social

#MedicalResearch
#CSLCentenaryFellowships
#WomenInSTEMM
@mcri.bsky.social

Translation for last year PhD students: You want to watch the ARC webpage tomorrow to see who will be looking for postdocs in 2026

Structural and mechanistic insights into translation initiation on the enterovirus Type 1 IRES Enteroviruses are a widespread and diverse set of pathogens responsible for over ~1 billion human infections annually. Upon cell entry, translation of the virus genome is mediated by an internal ribos...

Enteroviruses cause over a billion infections each year, but the details of how their genomes capture host ribosomes have remained elusive. I'm pleased to share a new preprint from Miguel in our group, providing some new insights into this problem:
www.biorxiv.org/content/10.1...

A new paradigm for outer membrane protein biogenesis in the Bacteroidota - Nature Structural and biochemical studies of the β-barrel-assembly machinery from Flavobacterium johnsoniae reveal a subunit composition and assembly that are distinct from those of the canonical Escherichia coli complex.

Nature research paper: A new paradigm for outer membrane protein biogenesis in the Bacteroidota

go.nature.com/3KvfHiG

A Protein Antibiotic Inhibits the BAM Complex to Kill Without Cell Entry Many antibiotics are ineffective against Gram-negative pathogens such as Pseudomonas aeruginosa because they cannot penetrate the bacterial outer membrane. Here, we show that protein antibiotics calle...

Check out our preprint in which we determine how a class of potent protein antibiotics specifically kill P. aeruginosa without a need to enter the cell.

doi.org/10.1101/2025...

This is work from my PhD in the lab of @rhyswg.bsky.social and many collaborators who contributed amazing data!

A Protein Antibiotic Inhibits the BAM Complex to Kill Without Cell Entry Many antibiotics are ineffective against Gram-negative pathogens such as Pseudomonas aeruginosa because they cannot penetrate the bacterial outer membrane. Here, we show that protein antibiotics calle...

This is an amazing paper led by the Grinter lab on bacterial protein antibiotics called pyocins and the mechanism by which they inhibit the BAM outer membrane complex. @rhyswg.bsky.social, @knottrna.bsky.social, @debnathghosal.bsky.social, @doylemt1.bsky.social, @fabianmunder.bsky.social

This work was a huge team effort led by the extremely talented @fabianmunder.bsky.social.

Many thanks and congratulations to everyone who contributed! Too many to thank here but check out the author list.

A Protein Antibiotic Inhibits the BAM Complex to Kill Without Cell Entry Many antibiotics are ineffective against Gram-negative pathogens such as Pseudomonas aeruginosa because they cannot penetrate the bacterial outer membrane. Here, we show that protein antibiotics calle...

The outer membrane of Gram-negative bacteria blocks many antibiotics. Our latest work reveals that L-type pyocins bypass this barrier by inactivating the BAM complex, killing Pseudomonas aeruginosa without entering the cell, providing a new blueprint for beating antibiotic resistance.

Code to complex: AI-driven de novo binder design In this review, Fox et al. discuss how artificial intelligence has transformed our ability to design new-to-nature proteins that bind target proteins with high affinity and specificity. The authors de...

Excited to share our new review on AI-driven protein design - from its origins to today’s breakthroughs, methods, potential, and challenges ahead !

www.cell.com/structure/fu...

The natural protein RcoM

New engineered protein shows promise as antidote for carbon monoxide poisoning
www.medschool.umaryl...

schedule introduction and membership Boston Protein Design and Modeling Club (BPDMC) is a community of computational protein engineers and modelers from both academia and industry. While we are based in Boston...

Fun fact: #bindcraft evolved from a binder design tutorial originally developed for BPDMC!

Come see @martinpacesa.bsky.social tonight at 7pm EDT in Room 181, Building 68, @mit.edu

"BindCraft: one-shot design of functional protein binders"

bpdmc.org

Fingers crossed. 🤞

Feels GPU related to me. 😒

Next-level hydrogenase fuel cell just dropped, congrats @rhyswg.bsky.social and @greening.bsky.social et al.!

Nanoengineered bioanode with oxygen-insensitive hydrogenase for sustainable energy harvesting from atmospheric hydrogen and waste gases Enzymatic biofuel cells (EBFCs) utilizing hydrogenases to oxidize hydrogen offer a sustainable approach to energy conservation. However, the oxygen se…

1/3 Electricity from air! In the top journal Nano Energy today, we report the first fuel cell that makes power from air alone. We achieved this by using the enzyme Huc to oxidize ambient hydrogen. This results in a continuous low-level power from air and higher outputs with industrial waste gases.

PM Mark Carney 🇨🇦
A new airlift of Canadian aid landed in Gaza today, with thanks to His Majesty King Abdullah II & our Jordanian partners.
Canada is dedicating more than $340 million in aid to address the humanitarian crisis in Gaza & we will ensure it moves forward at the necessary scale. #cdnpoli

In this system, bacteria detect phage infection through a sensor protein (YjbH) and respond by severing the infected part of the cell via aberrant division. The rest of the cell survives and continues growing happily, essentially, bacterial autotomy!

📣 New paper alert! Just out in Cell Reports! pubmed.ncbi.nlm.nih.gov/40644298/
Thrilled to share that we have discovered a brand-new anti-phage defense system! Bacteria have evolved various defense strategies (CRISPR etc) to counter phage attacks. We found a new one - fascinating and dramatic
⚔️🦠❄️🔬

CAPRI Docking

A small reminder to all structural biologists around working on biomolecular complexes: please consider sharing your complexes as targets for CAPRI - AI has not solved all structure prediction problems and there are still challenges! See www.capri-docking.org/contribute/

When’s the deadline for the next round?

ATP synthesis driven by atmospheric hydrogen concentrations | PNAS All cells require a continuous supply of the universal energy currency, adenosine triphosphate (ATP), to drive countless cellular reactions. The un...

ATP synthesis driven by atmospheric hydrogen concentrations www.pnas.org/doi/abs/10.1... #jcampubs

Excellent nanomolar peptide design success rates with BindCraft!

I am super excited to announce that I will be starting my lab at the Department of Pharmacology of the University of Zurich in Switzerland next year!