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Tracking the Endocytic routes of growth factor receptor complexes and their modulatory role on signalling

Final Report Summary - ENDOTRACK (Tracking the endocytic routes of growth factor receptor complexes and their modulatory role on signalling)

The ENDOTRACK project aimed at gaining conceptual advance into the signalling function of Growth factors (GFs) from an unconventional perspective, namely by exploring the role of endocytic trafficking in the modulation of GF signalling. It further aimed at translating the generated basic knowledge into novel opportunities for the development of a new generation of tools to combat diseases such as cancer and neurodegenerative diseases.

In order to achieve this mission, a multidisciplinary approach was implemented, involving in vitro, ex vivo and in vivo systems both in large scale screening and in more focussed screening settings. The project strategy delivered the proof of principle that it was possible to qualitatively and quantitatively modify the signal transduction output of a variety of GFs via the modulation of endocytic routes, with predictable consequences at the patho-physiological level.

ENDOTRACK was structured in five distinct, yet interrelated, Work packages (WPs) which analysed the trafficking routes of various GF complexes in cultured cells and defined the molecular machinery that undermined their transport using proteomics and functional genomics approaches. Moreover, information from cultured cells was integrated with in vivo studies on animal model systems and the relevance of the modulation of endocytic trafficking on signal transduction was tested in disease model systems.

Thus, a new generation of assays to measure GF trafficking and signalling was developed and an interface between these two fields was established. In addition, the project delivered a novel technology platform for high content and high throughput functional genomics studies based on Ribonucleic acid interference (RNAi) and quantitative multiparametric image analysis. The produced assays supported the identification of innovative key regulatory components and therefore, they could assist in the development of a new generation of diagnostic markers and potential targets for the modulation of GF signalling and the treatment of human diseases. The very stringent statistical control of quantitative data analysis introduced a new quality standard in the research files of GF signalling and trafficking.

Hence, ENDOTRACK's translational research was anticipated to have a strong impact on the innovation potential of basic research as well as on the European biotech and pharmaceutical industries. In order to maximise these potential benefits the acquired knowledge was disseminated at three levels, namely within the project consortium, to the interested scientific community and to the general public and potential stakeholders.