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Extracellular mechanisms regulating range and activity of egfr ligands


Secreted signalling molecules must reach their target cell to activate an appropriate response. In contrast to our extensive knowledge about intracellular signal transduction networks, the means by which the signalling molecules are transported and how their range of action is determined is poorly understood. Given the importance of the Epidermal growth factor (Egf) pathway in all animals it is very important to understand the extra cellular regulation in Egfr signalling. The aim of this proposal is to address the following:
1.How do the Egfr ligands spread in the extra cellular environment? Do proteoglycans modulate Egfr ligand activity/range?
2. Is endocytosis and/or transcytosis a significant physiological regulator of Egfr ligand activity and range? How is the stability of the ligands regulated?
3. What is the role of a conserved N-terminal sequence motif in three of the Egfr ligands? This work will not only increase our appreciation of the complexity of the regulation of Egf signalling, it could also have potentially important medical implications. I will learn advanced Drosophilae genetics and acquire a deeper understanding of developmental processes. I will also expand my knowledge in cell biological techniques and learn confocal microscopy. The most important impact will come from the very stimulating environment provided by the Cell Biology department at the host institute, the Laboratory of Molecular Biology. This will hopefully turn out to be a symbiotic interaction.


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MRC Laboratory of Molecular Biology
Hills road
CB2 2QH Cambridge
United Kingdom

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