Marisa Martin-Fernandez

Institute:Science and Technology Facilities Council, Oxford
Title:EGF receptor structure-function relationships in the cell nano-environment
Abstract:["The human epidermal growth factor receptor (EGFR) initiates signals for cell proliferation and transformation. This receptor has an extracellular growth factor-binding domain (ECD), a single-pass transmembrane region and an intracellular domain that has tyrosine kinase activity. The activation of the EGFR is triggered by the binding of small growth factor polypeptide ligands and involves the formation of dimers of these receptors. Oligomers are also commonly observed on cell surface, yet the lack of methods with sufficient resolution has hindered our understanding of oligomer structure and their functional role in EGFR signalling. We developed a number of methods to determine structure function relationships of EGFR complexes on the cell surface, including a super-resolution method based on fluorophore localisation imaging with photobleaching (FLImP), that reports the geometry and size of oligomers of the EGFR family on the cell surface with ~ >5 nm resolution. By using non-activating peptide markers and combining the FLImP super-resolution method with fluorescence resonance energy transfer to determine intra-receptor conformation and single particle tracking to investigate receptor dynamics, we are beginning to determine conformational changes and interactions in oligomers that regulate EGFR signal transduction across the plasma membrane on the cell nano-environment."]
Host:Paul Bergen en Henegouwen, van