Objectives: Establish NanoBRET and CETSA cellular lines for EGFR/BRAF; quantify intracellular engagement of top peptide and small-molecule interface hits; map pathway rewiring under interface modulation and benchmark against ATP-site inhibitors; establish resistance-evolution baselines; define cell-level go/no-go criteria to guide WP3 optimisation.
Expected results: Quantitative NanoBRET/CETSA engagement datasets; pathway-profiling resource and comparative analysis versus ATP-site drugs; validated decision-gates for chemical-series advancement; a resistance-trajectory dataset to benchmark the adaptive resilience of interface modulators.
Secondments: AuTh: Assay-based hits refinement (M20–23; 4 months); LEI: AI-assisted resistance-modelling inputs (M31–33; 3 months).
Integration: Provides the translational anchor for the consortium; feeds engagement and signalling constraints back to WP3 design streams and WP1 assay tuning.
Interdisciplinarity: Combines chemical biology, quantitative cell signalling, resistance biology and AI-guided interpretation.
