Position 3: Single-molecule FRET maps of kinase oligomerization and ligand-biased conformations

Objectives: Generate site-specific labelled EGFR/BRAF/LTK constructs; quantify monomer↔dimer equilibria and conformational states under AfBP locking; derive FRET-signature fingerprints predictive of interface-inhibitor activity; propose interface mutants as mechanistic controls for WP1 and WP3.

Expected results: A smFRET atlas across three kinases, including state distributions, kinetic-transition parameters and mutant-based mechanistic controls; open analysis pipelines and FAIR-released datasets; a methodological paper integrating smFRET with ATP-site–locked conformational mapping.

Secondments: VIB: Cryo-EM correlation of FRET-defined states (M19–22; 4 months); AZ: MD simulations for atomistic validation of conformational transitions (M30–32; 3 months).

Integration: Provides mechanistic fingerprints for WP1 assay calibration and guides WP3 hit prioritisation; anchors structural interpretation across WP2 and supports WP4 functional analysis.

Interdisciplinarity: Integrates single-molecule biophysics, structural biology (cryoEM) and computational modelling

DC3 (WP2) — Host: UoC (GR) – Prof Eleftheriadis (Start date: M4)

Host institution: University of Crete