The overall objective of this proposal is to provide Dr. Gonzalez-Quevedo with an extension of her training in order to broaden her expertise and advance her scientific career. Dr. Gonzalez-Quevedo has previously used molecular biology, biochemistry and cell biology approaches to the study of cancer. She now wants to train in in vivo analyses of the normal regulation of cell migration processes during development, as this is essential for understanding mechanisms underlying its miss-regulation during tumorigenesis. Regulation of migration and adhesive properties of cells is crucial for the correct morphogenesis of developing tissues, and disruption of these processes has been implicated in cancer invasion and metastasis. Eph receptors and their ephrin ligands are critical mediators of cell migration in different contexts. Despite the increasing knowledge regarding the function of Eph receptors and ephrin, very little is known about how they are regulated to switch between adhesion and repulsion responses.
The project aims to study how FGF receptor signalling regulates Eph receptor/ephrin-mediated cell adhesion and migration. I plan to use a synergistic combination of in vitro (biochemistry, cell biology, pharmacology) and in vivo approaches (boundary formation during hindbrain segmentation in zebrafish and chick) to dissect a molecular mechanism likely to be of importance for cancer invasion and metastasis. The project contributes to the improvement of science in Europe both by addressing a fundamental mechanism of clinical relevance, and by enabling significant new training in an expert laboratory in another European country.
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