Nicholas Polizzi, PhD, of Dana-Farber Cancer Institute

In a new study published in @natmethods.nature.com, @danafarber.bsky.social’s @nickpolizzi.bsky.social uses features from a pretrained neural network to train a logistic regression model, AF2BIND, which could be used for drug discovery and uncovering functional sites in proteins.

➡️ rdcu.be/e7SnX

Congratulations to @nickpolizzi.bsky.social and colleagues! They combine protein structure prediction with prediction of small molecule binding to map a wide range of functional sites on proteins. Way to boost the hunt for targetable (ligandable) sites!

I’m looking to hire a research technician for my lab at Harvard & DFCI, who would primarily work in the wet lab expressing and characterizing designed proteins, starting this summer. A great role for a recent college grad looking for an immersive research experience before grad school.

Mutant p53 protein accumulation is selectively targetable by proximity-inducing drugs - Nature Chemical Biology Exploiting the high abundance of mutant p53 protein, a small molecule was developed that specifically binds to p53-Y220C mutants and delivers a mitosis blocker, killing TP53-mutant cancer cells while ...

New paper from Will Gibson's lab showcases how induced proximity can be used to induce targeted protein mislocalization as a strategy to trigger cancer cell death.

Interesting, very interesting!!!!!

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

It was a pleasure to have you spend a part of your sabbatical with us!!!

Faculty/Health Educator Job: Assistant/Associate Professor, Chemical Biology at Dana-Farber Cancer Institute in 450 Brookline Ave, Boston, MA Assistant/Associate Professor, Chemical Biology job

We are looking to hire an Assistant/Associate Professor interested in creating an innovative (and exciting) program of research in chemical biology, medicinal chemistry, ML/AI, drug discovery - all in the context of cancer biology!
careers.dana-farber.org/job/11813/as...

Rapid clearance of achiral small-molecule drugs using de novo-designed proteins and their cyclic and mirror-image variants - Nature Biomedical Engineering Cyclic and mirror-image variants of de novo-designed proteins effectively bind and clear small-molecule drugs in vivo in less than 30 min, highlighting the applicability of computational tools to prod...

New paper from @nickpolizzi.bsky.social, Bill Degrado and Bobo Dang showing that de novo designed small molecule binding proteins can bind to the drug and clear it from the circulation in vivo. Read in Nature Biomedical Engineering!

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

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Characterization of PROTAC specificity and endogenous protein interactomes using ProtacID Here we describe ProtacID, a flexible BioID (proximity-dependent biotinylation)-based approach to identify PROTAC-proximal proteins in living cells. ProtacID analysis of VHL- and CRBN-recruiting PROTA...

Characterization of PROTAC specificity and endogenous protein interactomes using ProtacID

Ad for the Bioimage Analysis Beginnings Bootcamp at the Broad Institute. Where & When Broad Institute, 415 Main Street, Cambridge MA (in-person only) Monday–Friday, August 4–8, 20259:00 AM – 5:00 PM About the Bootcamp Learn core bioimage analysis skills using open-source tools for light microscopy in this hands-on, in-person course. The Bootcamp covers annotation, segmentation, and deep learning fundamentals. Fee: $600 (Academic/Non-Profit) | $1000 (Industry/For-Profit) For more information email ImagingAdmin@broadinstitute.org

BIG NEWS - for the first time ever, we're running a Bioimage Analysis Beginnings Bootcamp. Learn #bioimageanalysis from awesome folks, and gain familiarity with some new tools as well as how to pick the right tool in the first place. Aug 4th-8th - apply here (soon!) forms.gle/d2fCXsrWHVP8...

The cryo-em core at kumc is looking for a lab manager. This is an exciting opportunity to join a growing facility. kumc.wd5.myworkdayjobs.com/en-US/kumc-j...

Functional Spectrum of USP7 Pathogenic Variants in Hao-Fountain Syndrome: Insights into the Enzyme’s Activity, Stability, and Allosteric Modulation Hao-Fountain syndrome is a rare neurodevelopmental disorder caused by mutations in the de-ubiquitinating enzyme USP7 (Ubiquitin Specific Protease 7). Due to the novelty of the disease and its poorly u...

In related work @irinabezsonova.bsky.social lab showed how these activators can be used to correct effects of USP7 mutations that are associated with Hao-Fountain syndrome www.biorxiv.org/content/10.1...

Small-molecule allosteric activator of ubiquitin-specific protease 7 (USP7) Ubiquitin-specific protease 7 (USP7) is a deubiquitylase essential for cell homeostasis, DNA repair, and regulation of both tumor suppressors and oncogenes. Inactivating USP7 mutations have been assoc...

NEW PREPRINT ALERT: Buhrlage lab in collaboration with @irinabezsonova.bsky.social has developed a new class of USP7 activators!

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

Zero-shot design of drug-binding proteins via neural selection-expansion Computational design of molecular recognition remains challenging despite advances in deep learning. The design of proteins that bind to small molecules has been particularly difficult because it requ...

Super excited to share a new preprint from our lab on design of small-molecule binding proteins using neural networks! The paper has a bit of everything. A new graph neural network, new design algorithms, and experimental validation. www.biorxiv.org/content/10.1...
🧵🧪

We provide a new checklist for selecting & using chemical probes—valuable for researchers, journal editors, reviewers, and vendors. Ensure best practices in chemical biology! 🧪✅

🔗 Supplementary material: ars.els-cdn.com/content/imag...

#ChemicalProbes #DrugDiscovery #ChemicalBiology

Mechanisms and functions of lysosomal lipid homeostasis In this review Ebner et al. summarize and discuss the rapidly increasing knowledge regarding the mechanisms of lysosomal lipid turnover and export as well as the pathways for the homeostatic control a...

Review @cp-cellchembiol.bsky.social @volkerhaucke-lab.bsky.social
Mechanisms and functions of lysosomal lipid homeostasis
www.cell.com/cell-chemica...

Make use of our public database of Postdoc fellowships (private foundations, federal agencies). It's downloadable and free.

We list 290 different fellowships and funding opportunities, along with description, deadline, amount, and eligibility criteria
Download here: research.jhu.edu/rdt/funding-...

Sexually dimorphic dopaminergic circuits determine sex preference Sociosexual preference is critical for reproduction and survival. However, neural mechanisms encoding social decisions on sex preference remain unclear. In this study, we show that both male and femal...

Potential explanation for the results of the most recent elections?
Seems like H. sapiens can't fight biology? "Both male and female mice exhibit female preference (under normal conditions) but shift to male preference when confronted with survival threats."
www.science.org/doi/10.1126/...

Scratching promotes allergic inflammation and host defense via neurogenic mast cell activation Itch is a dominant symptom in dermatitis, and scratching promotes cutaneous inflammation, thereby worsening disease. However, the mechanisms through which scratching exacerbates inflammation and wheth...

Go ahead - I know you want to!
Just scratch that itch!!!
www.science.org/doi/10.1126/...

What do you get when you put @aledmedwards.bsky.social and me in front of a microphone? You get a great conversation about #openscience, #ChemicalProbes, and a crazy goal about creating tool compounds and probes for every protein in the human proteome by 2035. creators.spotify.com/pod/show/tar...

Our upcoming #TPD webinar features an intriguing talk "Ub or Not Ub: Decoding Ubiquitin-Dependent and Independent Degradation Pathways" by Itay Koren (Bar-Ilan University). Tomorrow at noon EST - www.danafarbertargetedproteindegradation.org

An in-cell approach to evaluate E3 ligases for use in targeted protein degradation. www.biorxiv.org/content/10.1101/2024.12....

Tricking cells into trashing cancer In a study published today in the Journal of Clinical Investigation, Fred Hutch Cancer Center cancer chemical biologist Behnam Nabet and his collaborators describe how they used targeted protein degra...

In a study published today in @jclinical-invest.bsky.social, @behnamnabet.bsky.social and collaborators describe how they used targeted protein degradation in mice to rapidly destroy lung and pancreas tumors caused by a variant of a commonly mutated, cancer-driving gene.

The huge protein database that spawned AlphaFold and biology’s AI revolution Pioneering crystallographer Helen Berman helped to set up the massive collection of protein structures that underpins the Nobel-prize-winning tool’s success.

Ever wonder where Nobel Prize-winning AlphaFold got its training data? Read how pioneering crystallographer Helen Berman helped build the Protein Data Bank as a home for more than 200,000 protein structures that would come to shape AI and protein prediction ➡️

Protein-Based Degraders: From Chemical Biology Tools to Neo-Therapeutics The nascent field of targeted protein degradation (TPD) could revolutionize biomedicine due to the ability of degrader molecules to selectively modulate disease-relevant proteins. A key limitation to ...

Excited to share this beast of a review on the potential of protein-based degraders from trainees who are all not on the Sky! Herein we cover choice of binders, selection strategies, E3 ligases, and DELIVERY! pubs.acs.org/doi/10.1021/...

Image of the job posting (see URL for full text instead)

We've a postdoc opening for our lab at the Broad: Cambridge MA!

Must have experience in toxicology + data science

Work on the wonderful OASIS dataset we are producing... Cell Painting, transcriptomics, proteomics in various liver cell and tissue models!

broad.io/mlcbpostdoc

The Young Scientist Award of @gdchbiochem.bsky.social of @gdch.bsky.social is open for nominations. If you know an excellent candidate, who defended their PhD or had a publication in 2024 in the field of biochemistry (or related), strongly consider nominating them. en.gdch.de/network-stru...