By evolving a flavoprotein in mammalian cells, a super-fast, genetically encoded photocatalyst called Lantern was developed, allowing the mapping of dynamic RNA and protein organization at high spatio...

Aberrant protein-protein interactions (PPIs) drive myriad diseases. Inhibiting these PPIs often relies on discovering molecules that bind to one of the proteins and hoping that this binding inhibits t...

Proteina-Complexa combines joint sequence-structure generation in a continuous latent space with inference-time search for de novo protein binder design. In a massive-scale experimental benchmark — o...

How an innovative UChicago laboratory built a fast-moving platform to target "undruggable" cancer proteins and train the next generation of scientific leaders

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans...

At public and private universities across the country, high-impact science is being damaged and derailed.

The NIH’s spending on new medical research is significantly slower than in previous years, leaving confused scientists in the lurch.

Developing molecules that selectively bind targets of interest remains a critical bottleneck in biological research and biotechnology. Here, we present a workflow that leverages the Phage-Assisted Non-Continuous Selection for Binders (PANCS-Binders) technology for rapid de novo binder discovery. To directly assess the speed and utility of the approach, we pursued three cancer-related targets: NSD3, NMNAT2, and CSF1R. Within 26 days, the PANCS-Binders workflow yielded sequence- and function-verified binders for all three targets with nano-to-micromolar affinities. By incorporating an NSD3 binder into an engineered E3 ligase, RNF8, we developed an NSD3 degrader that potently depleted endogenous NSD3 and inhibited colorectal cancer cell proliferation. We then applied this degrader to reveal previously unknown NSD3 dependencies in ovarian cancer cell lines, uncovering new therapeutic vulnerabilities. Together, our work establishes a robust workflow for accelerated binder discovery and demonstrates how binders can expedite chemical biology discovery and biotechnology development.

Protein binders are fundamental tools in chemical biology, key components of biotechnologies, and the foundation of biologics-based medicines. However…

RNAs preferentially localize across virtually every subcellular compartment, from membrane-bound organelles, membrane-less condensates and even the ce…

Building abrighter future. IDefine is committed to identifying life-changing treatments & cures for those with Kleefstra syndrome (KS), a neurodevelopmental disorder caused by a loss of function in on...

Protein binders are fundamental tools in chemical biology, key components of biotechnologies, and the foundation of biologics-based medicines. However…

Abstract. Therapeutic modalities to programmably increase protein production are in critical need to address diseases caused by deficient gene expression v

Combining bioorthogonal protecting groups with localized catalysts that can unmask them is a powerful approach to spatially and temporally modulate molecular activity. Enzymes are appealing catalysts ...

Compartmentalization by organelles and the dynamic control of protein localization within these compartmentalized spaces are key mechanisms for regulating biological processes in eukaryotic cells. Here, we present a bottom-up approach for constructing cell-sized liposomes (giant unilamellar vesicles, GUVs) encapsulating an artificial organelle with chemically controlled protein localization. In this system, proteins fused to Escherichia coli dihydrofolate reductase are rapidly recruited on demand from the inner solution to the interior of a DNA-droplet-based (“nucleus”-like) organelle within GUVs upon addition of a synthetic, DNA-binding trimethoprim derivative to the external solution. By coupling this system with a sequence-specific protease, we constructed a synthetic cell platform that enables chemically induced, multistep cascade reactions─including protein relocalization, organelle-specific enzymatic activity, and product release from the organelle─that culminate in the control of synthetic-cell phenotypes, such as pore formation in the GUV membrane. This work provides a versatile platform for the bottom-up creation of eukaryotic-like synthetic cells with sophisticated and programmable functions.

Creating artificial organelles that sequester and release specific proteins in response to a small molecule in mammalian cells is an attractive approach for regulating protein function. In this work, ...

Proteins that bind to a target protein of interest, termed "binders," are essential components of biological research reagents and therapeutics. Target proteins present multiple binding surfaces with ...

ChemBioVIII – Reunión Bienal GEQB-RSEQ | 105 followers on LinkedIn. Where Chemical Biology Meets Innovation | Official page of ChemBioVIII – the 8th Biennial Meeting of the Chemical Biology Specialize...

Bacterial ATP-binding cassette (ABC) transporters can be utilized and engineered to transport non-canonical amino acids into Escherichia coli for highly efficient synthesis of proteins with novel func...

De novo binder discovery is unpredictable and inefficient due to a lack of quantitative understanding of protein-protein interaction (PPI) sequence-function landscapes. Here, we use our PANCS-Binder t...