Thesis subject: Lipid Droplets as Biophysical Models for Understanding Viral Replication: Molecular Mechanisms of Dengue Capsid Protein Binding Probed by Neutron Scattering (LYON)

You will join the Large-Scale Structures group at the Institut Laue-Langevin (ILL), the world’s leading neutron science facilities, located in Grenoble, France. The ILL provides the scientific community with access to the world's most intense continuous neutron flux, hosting a broad suite of instruments for structural biology, soft matter, and surface science, including small-angle neutron scattering (SANS/USANS) instruments (D11, D22, D33) and the neutron reflectometers (D17, Figaro). These instruments exploit contrast variation, a powerful neutron technique, to resolve molecular-scale structures at complex interfaces invisible to other probes.

The aim of the PhD project is to understand the molecular mechanisms by which dengue virus capsid proteins (DENV-C) bind to lipid droplet (LD) surfaces, a process central to viral replication. Dengue fever infects over 400 million people annually across 100 countries, yet the molecular interactions underpinning DENV-C recruitment to LDs mediated by the LD-surface protein Plin3 still remain poorly understood. The novelty of the project lies in deploying quantitative neutron scattering techniques (SANS/USANS and neutron reflectivity with contrast variation) to directly probe the structure and interactions of DENV-C and its peptide analogues with well-defined artificial lipid droplet (ALD) models and Langmuir monolayers incorporating Plin3. This will disentangle specific protein-Plin3 interactions, yielding mechanistic insights to inform future anti-dengue strategies.

The student will benefit from a rich interdisciplinary collaboration with partners at the University of Bristol (ALD and liposome preparation), the University of Manchester (peptide synthesis), the Jerzy Haber Institute in Krakow, Poland (Plin3 expression), and the University of Galway, Ireland (molecular dynamics simulations).