Marzo 2026

Martedì 31
- 11:45 - 12:30

Centre de Lutte Contre le Cancer Eugène Marquis

Avenue de la Bataille Flandres Dunkerque

Ille-et-Vilaine

Bretagne

Dr. Nishant KUMAR - Engineering Supramolecular Polymer Membrane Mimetics to Elucidate the Dynamic Assembly and Activation Mechanism of IRE1

Name: Dr. Nishant KUMAR - Engineering Supramolecular Polymer Membrane Mimetics to Elucidate the Dynamic Assembly and Activation Mechanism of IRE1
Start: 2026-03-31T11:45:00+02:00
End: 2026-03-31T12:30:00+02:00
Location: Centre de Lutte Contre le Cancer Eugène Marquis

Engineering Supramolecular Polymer Membrane Mimetics to Elucidate the Dynamic Assembly and Activation Mechanism of IRE1

Martedì 31 marzo, 11:45

Passato

200

Engineering Supramolecular Polymer Membrane Mimetics to Elucidate the Dynamic Assembly and Activation Mechanism of IRE1

Dr Nishant KUMAR

INSERM UMR U1242 – OSS – PROSAC Team, RENNES

CNRS UMR 6226 – ISCR Rennes Institute of Chemical Sciences, COrInt Team

Abstract
This project is embedded within a larger multidisciplinary effort that combines three complementary synthetic platforms to address fundamental questions regarding the molecular mechanisms governing IRE1 activation. IRE1 is a master regulator of the unfolded protein response (UPR), a signaling pathway that safeguards cellular proteostasis. Through different pathways, IRE1 governs cellular life-or-death decisions and aims at restoring ER homeostasis. Despite extensive studies, key mechanistic questions remain unresolved: How does IRE1 luminal domain senses ER stress and what precisely drives IRE1 oligomerization? How is luminal stress sensing coupled to cytosolic catalytic activation?
Complementing the other approaches of the project, my work aim is to recreate the dynamic nature of the ER membrane using a supramolecular polymer-based synthetic mimic. To do that, we will be using water-soluble benzene-1,3,5-tricarboxamide (BTA) discotics that self-assemble into one-dimensional polymers in aqueous solution through reversible monomer exchange. By orthogonally functionalizing BTA monomers to conjugate both luminal and cytosolic domains of IRE1, we will generate a pseudo–full-length construct (BTA–IRE1) in which the discotic core replaces the transmembrane domain, enabling dynamic oligomerization along a supramolecular wire. Co-assembly with non-functionalized BTA monomers will permit precise control over local IRE1 density, thereby mimicking varying ER stress conditions while preserving dynamic reorganization. By integrating supramolecular chemistry with protein engineering, this platform will allow us to systematically probe how luminal domain engagement, BiP regulation, phosphorylation state, and local concentration drives oligomerization and enzymatic activation.

Marzo 2026

Martedì 31
- 11:45 - 12:30

Additionnal information

Compléments d'information

No input

A proposito del luogo

Centre de Lutte Contre le Cancer Eugène Marquis

Avenue de la Bataille Flandres Dunkerque

Ille-et-Vilaine

Bretagne

UID

Fonte: UMR INSERM 1242 Oncogenesis Stress Signaling (OSS)

Aggiornato il 31 marzo 2026

Dati aperti · Licence Ouverte 2.0