Centro de Biología Molecular Severo Ochoa

RNA ‐related functions of BRCA2 in transcription, replication, and genome stability

BRCA2 is a central tumor suppressor protein best known for its roles in homologous recombination and replication fork stability. Increasing evidence, however, positions BRCA2 at the interface of transcription and replication, where it preserves genome stability under transcriptio...

Regional differences in dendritic spine morphology and innervation of the trisynaptic circuit of a mouse model of GSK-3β overexpression

Abstract The trisynaptic circuit, which includes the entorhinal cortex (EC), dentate gyrus (DG), and Cornu Ammonis (CA1, CA2, and CA3) of the hippocampus, is among the regions first affected by Alzheimer’s disease (AD). Glycogen synthase kinase-3β (GSK-3β) has emerged as a key en...

Inositol Hexakisphosphate Promotes Open Pore State in HIV Capsid Protein Lattice by Reconfiguring Subunit Contacts

Abstract The mature human immunodeficiency virus (HIV-1) capsid is composed of approximately 250 capsid protein hexamers, each containing a central pore delimited by a β-hairpin and an α-helix from each monomer. The cellular metabolite inositol hexakisphosphate (IP6) binds this p...

Astrocytic PI3Kα controls synaptic plasticity and cognitive function via serine metabolism

Astrocytes modulate neuronal activity by gliotransmission and through metabolic regulation, yet the relationship between these functions remains poorly understood. Here we show that phosphatidylinositol 3-kinase (PI3K) signaling in astrocytes controls synaptic plasticity and memo...

A Drug‐Gated, Modular STAb‐T Immunotherapy With External Control

ABSTRACT Living cell therapies lack robust, reversible mechanisms for externally controlling therapeutic activity after administration, limiting their safety and clinical adaptability. Here we engineer a drug‐gated cellular immunotherapy platform in which T cells function as prog...

Proteo‐Metabolomic Profiling of PMM2 ‐ CDG Reveals Dysregulation of Retinoic Acid Synthesis, Myo ‐Inositol, and the Hexosamine Pathway

ABSTRACT Phosphomannomutase deficiency (PMM2‐CDG), the most common congenital disorder of glycosylation (CDG), is characterized by multisystem involvement and a lack of disease‐modifying therapies. While previous transcriptomic studies have uncovered disrupted cellular pathways,...