International Associated Laboratory (IAL) GHOST GLY : GHOST GlyCo Proteome

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ULille Horizontal Noir            Inserm rvb                      Yale University                              

The GhostGly project will consist in the development of a tight collaboration to identify glycosylation on membrane ghost proteins and link these proteins to dysregulated intracellular signalling pathways in ovarian cancer of different phenotypes (mutation profile, type) compared to a control. The goal of GhostGly is to identify specific membrane ghost proteins with aberrant glycosylation as a potential target for immunotherapy. The GhostGly project aims to identify the protein interaction partners of selected AltProts to approach their function in ovarian cancer. We will focus our interest on membrane ghost proteins and will try to establish the nature of their glycoforms. Thus, finding specific membrane ghost proteins with altered glycosylation involved in ovarian cancer oncogenesis or EMT translation will be of great importance. GhostGly will give us the knowledge to find specific targets common to all ovarian cancer sub-types.

The four specific objectives of GhostGly are therefore, 1) to identify interaction partners of AltProts by crosslinking MS (XL-MS), thereby assigning cellular functions to AltProts; 2) to identify the glycoforms of membrane ghost proteins in ovarian tumors; 3) to use targeted interactomics to identify target-specific PPIs and validate membrane AltProts functional interactome; and 4) to perform phenotypic studies of the selected AltProts by disturbing their expression. Involvement of the AltProts in resistance mechanisms will as well be studied by comparing the functional interactome network from untreated cells or cells upon treatment with chemotherapeutic drugs known to induce resistance. The obtained data will help to determine the oncogenesis of ovarian cancer by identifying new biomarkers and therapeutic targets.