Scripps Research Institute

RiboTRAP-seq identifies spatially distinct functions for the anterior and posterior intestine in immune and metabolic regulation in Caenorhabditis elegans

Abstract The intestine integrates food-derived cues to coordinate organismal physiology, yet the molecular specialization of discrete regions along the intestinal epithelium remains unclear. Here, we generate cell type-specific translatomes of the Caenorhabditis elegans intestine...

Tryptoline stereoprobe elaboration identifies inhibitors of the GRPEL1–HSPA9 complex

Abstract Activity-based protein profiling has identified hundreds of human proteins from diverse classes that react at cysteine residues with stereochemically defined electrophilic compounds (stereoprobes). The structure–activity relationships underlying these stereoprobe–protein...

Orthogonal Fc engineering enables multiplexed delivery of mRNA-encoded bispecific antibodies that constrain viral escape

The continuous antigenic evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has repeatedly undermined the effectiveness of monoclonal antibody (mAb) therapies, underscoring the need for innovative approaches that improve therapeutic mAb breadth and durabili...

Self-Assembling Nanoparticles to Assess Multivalent Interactions between Influenza A Virus Hemagglutinin and Glycan Surfaces

Abstract The multivalent display of surface glycoprotein hemagglutinin (HA) on Influenza A viruses (IAVs) enhances the overall binding avidity to sialylated glycans on host cell surfaces. While precomplexing HA trimers with antibodies increases multivalency and avidity, this meth...

Programmed inhibition of an innate immune receptor via de novo designed transmembrane proteins

Transmembrane domains of immune complexes transmit precise signals across lipid bilayers. Probing their interactions has the potential to yield mechanistic insights relevant to therapeutic design. However, our capability to generate molecules that bind lipid-embedded sites is lim...

Antibody Hotspot-Centric de Novo Design of Peptide Inhibitors of Influenza A Virus Membrane Fusion

Abstract Here we report the applicability of a hotspot-centric approach for de novo computational design of l-peptides based on crystal structures of antigen–antibody complexes. Broadly neutralizing antibodies (bnAbs) FI6v3 and CR9114, which target influenza A virus hemagglutinin...

Patient-facing artificial intelligence in primary health care: a scoping review of literature through early 2025

Abstract Background Patient-facing artificial intelligence (AI) tools are increasingly accessible to the public, but evidence on their development and impact in primary health care (PHC) remains limited. This study aimed to map the literature on patient-facing AI tools in PHC, in...

Reproducibility, Replicability, and Research Quality in Homogeneous Catalysis

Abstract Researchers from all sectors of homogeneous catalysis convened in response to concerns regarding reproducibility in science to analyze the issue and provide recommendations. In addition to an in-person workshop, the group engaged the broader homogeneous catalysis communi...

Drug‐Derived Tetrahydropyrazines for Late‐Stage α ‐ and β ‐Functionalization of Piperazine‐Based Pharmaceuticals

ABSTRACT Piperazine is one of the most prevalent saturated nitrogen heterocycles in pharmaceuticals, yet late‐stage access to α ‐ and β ‐substituted piperazine analogues remains challenging. Here, we report a flavin‐photocatalyzed platform that converts complex piperazine‐contain...

Iron-catalyzed [1+1+1] cyclopropanation by sequential coupling of an ester to two carbenes

Traditional precious metal catalysis benefits from well-characterized inner-sphere elementary steps in which a single complex binds and unites substrates at the metal center. By contrast, base metal catalysts have recently demonstrated competence in cross-coupling transformations...

Single-component self-assembling protein nanoparticles displaying stabilized prefusion-closed hemagglutinin trimers for influenza vaccine development

ABSTRACT Current influenza vaccines primarily target hemagglutinin (HA), the major surface glycoprotein and principal determinant of neutralizing antibody (NAb) responses. However, antigenic drift and shift, together with HA’s intrinsic metastability and low-pH sensitivity, pose...

Artificial hibernation reveals synaptic engram architecture associated with memory retention

Memories leave lasting physical changes at the synaptic level. Although stable, larger spines are thought to support memory, the high turnover of dendritic spines and the drifting of neuronal representations after memory formation suggest alternative possibilities. To elucidate t...

Photoproximity labeling of c-Myc reveals SLK as a cancer-specific co-regulator

Transcription factors (TFs) have long been aspirational therapeutic targets for the treatment of diseases, as their dysregulation is a common mechanism for altered cell states. Despite this, many TFs implicated in disease have disordered structures and lack canonical binding pock...

Hepatocyte-intrinsic ER stress and NRF2 initiate primary sclerosing cholangitis, providing therapeutic insights

primary sclerosing cholangitis (PSC) is a severe liver disease that can progress to cholangiocarcinoma. Therapeutic development has been hindered by the rarity of PSC and by its poorly understood origin, which reflects incompletely defined genetic and environmental risk factors....

Discovery of Sphaeriaurantinsas Rapid-Acting Antiplasmodialswith Dual Activity in Blood and Liver Stages

Abstract The rapid emergence of resistance in the malaria-causing protozoan Plasmodium falciparum has heightened the demand for treatments with novel modes of action. Having evolved to produce a myriad of structurally diverse natural products (NPs) as defenses against soil-dwelli...