CORDIS - Resultados de investigaciones de la UE
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Parallel use of yeast and mammalians for dissecting secretory traffic

Final Activity Report Summary - SECRETORY TRAFFIC (Parallel use of yeast and mammalians for dissecting secretory traffic)

Intracellular traffic is the process by which cells transport proteins, lipids and sugars to their final destinations. The elucidation of the molecular and functional organisation of membrane traffic is one of the central goals of modern cell biology and will have a profound impact on our understanding of the pathogenesis of several human diseases and on the development of biotechnological tools. A complex system such as traffic may present defects which can contribute to disease, such as altered glycosylation of membrane receptors, the mistargeting of key regulatory proteins and the disregulated secretion of proteases. Such defects may be important in the field of oncology where, for example, protease secretion is a critical component of the invasive potential of cancer cells.

The goal of the host laboratory was to understand the organisation of the cell trafficking pathways at both the morpho-functional and the molecular level and to apply this knowledge to the treatment of human diseases. The host institution possessed strong expertise in the technologies required to study intracellular membrane traffic. It had developed, and was internationally recognised for this, sophisticated morphological and molecular biology approaches to study various aspects of membrane traffic.

The study of membrane traffic was traditionally developed in two main types of organisms, namely mammals and yeast. The objective of the Marie Curie transfer of knowledge programme was to combine these two systems by integrating competence in yeast research into the host institution, thus accelerating our understanding of how these systems worked and their relevance to human diseases. A more experienced researcher and an experienced researcher were recruited to assist in the transfer of knowledge to members of the host institution and to implement the principle aspects of the research in yeast. A laboratory was set up with the necessary equipment for yeast work, either by acquiring new equipment or by adapting equipment that already existed in the institute, and by providing access to all of the facilities and infrastructure at the institute. The principal aim of the project, i.e. a fully functional yeast facility with all the necessary equipment for yeast work, was available at the host institute by the time of the project completion.

A number of areas of research were chosen and would benefit from combining yeast and mammalian studies that addressed some of the main interests of the groups working in the institute, together with considerations of the technologies available in both organisms. These involved direct comparisons of evolutionarily conserved protein complexes involved in membrane traffic in both systems, advanced microscopy to study morphology, functional assays in yeast to study the role of mammalian proteins and the generation of yeast systems for screening interactions between mammalian proteins. An illustration of the success of the transfer of knowledge was the award of a grant from the Telethon Foundation to the institute that involved a comparative yeast and mammalian study of the sedlin/Trs20 gene, whose mutation led to the X-linked genetic disorder called SEDT.

In line with the objectives of the Marie Curie development scheme for the transfer of knowledge, the recruitment of outside researchers to assist in the transfer of knowledge promoted the mobility of researchers, which was further enhanced by the provided teaching and training, which consolidated and widened the researchers' career prospects.