November 12th, 2026, 1:30pm
ImmunoConcept's seminar, BBS amphitheater
Alba HERRERO DEL VALLE, MSCA Postdoctoral Fellow in the Molecular Diversity of Microbes Lab (PI: Aude Bernheim, Pasteur Institute, Paris).
Title: From Homeostasis to Immunity: Molecular Principles of Signal Recognition
Abstract:
My research focuses on understanding how cells distinguish self from non-self at the molecular level. To uncover the molecular principles driving this, I employ advanced imaging techniques, from cryo-EM of individual protein complexes to cryo-ET of processes within the cell, building a multi-scale picture of how signaling is controlled.
To illustrate that, I will present two projects I worked on, beginning with MDA5, a human innate immune sensor that must precisely identify long viral dsRNAs while ignoring abundant cellular RNAs. Focusing on a gain-of-function mutant (M854K) that causes severe autoimmune disease, we investigated the molecular basis for its aberrant activity. Our cryo-EM structures revealed that, through an allosteric mechanism, this mutation disables the ATP-dependent proofreading step that is essential for ignoring self-RNA. This loss of fidelity leads to constitutive interferon production and provides a powerful example of how a failure in molecular recognition drives pathology.
I will then shift to my recent work exploring how discoveries in prokaryotic immunity can illuminate conserved pathways in humans. We characterized Eleos, a bacterial antiphage system that is an homolog of the GIMAP family of immunity-associated GTPases. Using in-situ cryo-electron tomography, we directly visualize Eleos-mediated structural collapse of a viral membrane compartment within infected bacterial cells, associated with the arrest of viral transcription and replication. We found this principle is conserved, as human GIMAP5 can restrict SARS-CoV-2 infection, likely by targeting a viral entry stage at the endosome.
These projects demonstrate that directly visualizing molecular events is essential for discovery, and these advanced imaging approaches will be central to tackling new questions in immunological recognition.