Laboratory of Chemical and Biological Probes

Catalytic pKa Attenuation in a Hydrolytic Metalloenzyme by Genetic Code Expansion Hydrolytic metalloenzymes employ Lewis-acidic metal cofactors to activate water molecules, generating nucleophilic hydroxide species that facilitate catalysis. Their catalytic efficiency across a wide...

Still obsessed with histidine (and its mimics)! Our latest work from Benjamin 🎉 uses genetic code expansion—tuning the primary coordination sphere of a dizinc metallohydrolase—lowering the catalytic pKa and boosting activity up to 5x at acidic pH. Check it out! doi.org/10.1021/acs.biochem.5c00768

A Ratiometric pH Sensor for Gram-Positive and Gram-Negative Bacteria Fluctuating environments can lead to phenotypic heterogeneity within a monoclonal bacterial population, especially in response to antibiotics or the human immune system. Methods are required to analyz...

Congratulations to @dorotheakossmann.bsky.social! Her paper describing a novel sensor for bacterial pH just appeared online. Great collaboration with @ayaiizuka.bsky.social and Nina Khanna within the @nccr-antiresist.bsky.social! @chem.uzh.ch
pubs.acs.org/doi/10.1021/...

They say the sincerest form of flattery is mimicry, and we really love histidine! ❤️ Check out our most recent work on histidine mimics: Genetic incorporation of diverse non-canonical amino acids for histidine substitution. www.biorxiv.org/content/10.1...

UZH: PhD Position in Redox Chemical Biology We are a dynamic, interdisciplinary, medium-size lab working at the interface of chemistry and biology. We work on the development of probes to visualize and control biological processes in living sys...

We are hiring! Excited about redox chemical biology? Help us discover what controls the redox state of the Golgi apparatus. Also, please help us spread the word by reposting this ad. Apply here: jobs.uzh.ch/job-vacancie...

Profiling the proteome-wide selectivity of diverse electrophiles - Nature Chemistry Covalent inhibitors are powerful entities in drug discovery. Now the amino acid selectivity and reactivity of a diverse electrophile library have been assessed proteome-wide using an unbiased workflow...

How can we study target engagement and selectivity of covalent inhibitors? Which electrophilic probes are best suited to study a certain amino acid?

Our study on "Profiling the proteome-wide selectivity of diverse electrophiles" is published in Nature Chemistry.(1/7)

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

Congratulations to Doro for another presentation prize! This time for her talk at SCF ChemBio in Paris.

The @locbp.bsky.social @chem.uzh.ch developed a gene expression reporter system based on the coexpression of the protein of interest BiP/GRP78 and the reporter HaloTag. chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/...

Two‐Color Timestamping of Gene Expression with a Chemigenetic Reporter System A chemigenetic reporter assay is developed that enables monitoring of BiP/GRP78 expression, an important chaperone and key regulator of the unfolded protein response. The system is based on the coexp....

Congratulations to Hen (again)! Her paper, in collaboration with Jade, Juan, and the EPFL ACCESS team was just published. The paper describes a chemigenetic gene reporter tool for time-stamping and pulse-chase-type experiments.
chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/...

Congratulation's to Hen! Great job presenting her chemigenetic gene expression reporter system!

Potent Inducers of Paraptosis through Electronic Tuning of Hemicyanine Electrophiles Paraptosis is a distinct form of programmed cell death characterized by cytoplasmic vacuolization, mitochondrial swelling, and endoplasmic reticulum (ER) dilation, offering an alternative to apoptosis...

Congrats to Juan! His discovery of hemicyanines as potent activators of paraptotic cell death has just been published! With great contributions from Jade (initial observations of ER swelling) and Craig (crucial supporting experiments)!
pubs.acs.org/doi/10.1021/...

Fluorescence Lifetime Multiplexing with Environment‐Sensitive Chemigenetic Probes HaloTag (HT) is a versatile self-labeling protein that has been widely adopted in fluorescence microscopy. Besides its established use as an intensity-based marker and sensor, interest in using HT fo....

Happy to share the results of a fun side project in which we used the COUPY dye and mutants of HaloTag7 to show that changes in fluorescence lifetime correlate with the polarity of the protein binding pocket!
chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1...
#FLIM #fluorescence #HaloTag

UZH: PhD position in Chemical Biology In the Laboratory of Chemical and Biological probes (PI: Pablo Rivera Fuentes), we do research at the interface of chemistry and biology, particularly in the fields of redox biology, development of im...

🚨Open PhD positions in chemical biology!🚨

Join us in developing chemigenetic probes for imaging and sensing.

⚗️🧫Experience in chemical synthesis and/or protein engineering?

🗻🇨🇭Love mountains, chocolate, and a safe, diverse, and engaging environment?

Apply (or re-post)!
jobs.uzh.ch/job-vacancie...

🚨 PhD Opportunity!

Passionate about enzyme engineering or genetic code expansion? 🧬 Our lab is hiring a PhD student!

🔬 Exciting interdisciplinary research
🤝 Engaging environment 🌱

📄 Does this sound like you, apply now! ⏳🔗
📢 Know someone? Share this! 🔄

jobs.uzh.ch/job-vacancie...

Looking for a PhD candidate to join my group at the University of Zurich If you are an excellent and motivated student🧑‍🔬and want to integrate organic synthesis, photochemistry and redox chemistry in a research🧪 we want to know more about you! More info: www.stacko.group Appreciate sharing the post.

Characterization of the Glutathione Redox State in the Golgi Apparatus Redox homeostasis is crucial for cell function, and, in eukaryotic cells, studying it in a compartmentalized way is essential due to the redox variati…

Now online at a peer-reviewed journal, Carla's careful characterization of the redox state of glutathione in the Golgi apparatus: www.sciencedirect.com/science/arti...

Hydrophobic tuning with non-canonical amino acids in a copper metalloenzyme Hydrophobicity controls many aspects of protein and enzyme function. Although hydrophobic tuning can be achieved to a limited extent with canonical amino acids, the incorporation of non- canonical ami...

Exciting news from the lab! Our first preprint, “Hydrophobic Tuning with Non-Canonical Amino Acids in a Copper Metalloenzyme” is now available.
In this study, we rewrite the rules of enzyme engineering with a cyclic, hydrophobic twist that’s anything but ordinary.
🔍: www.biorxiv.org/content/10.1...

Congratulations to @puentene.bsky.social, who won the best poster award at #SMPS24 @smps4.bsky.social!!

Another brilliant session by Pablo Rivera-Fuentes from the University of Zurich on 'Single-Molecule Protein Identification using Blinking Patterns.'
#SMPS4

Characterization of the Glutathione Redox State in the Golgi Apparatus Redox homeostasis is crucial for cell function, and, in eukaryotic cells, studying it in a compartmentalized way is essential due to the redox variations between different organelles. The redox state ...

Just out on bioRxiv, Carla Miró reports the first quantitative determination of the redox state of glutathione in the Golgi apparatus. Spoiler alert: it is very oxidized and in relatively low concentrations!
www.biorxiv.org/content/10.1...

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Long overdue, we have left the propaganda machine formerly known as Twitter and will be posting exclusively here!