Computational reconstruction of protein-protein interaction networks involved in the pathogenesis of Cerebral Cavernous Malformations.

Cerebral Cavernous Malformations (CCM) are brain vascular malformations which occur in one person out of 200. Their consequences are devastating as they provoke epilepsy, stroke and many neurological disorders. CCM develop only in low blood flow venules and not in arteries in which the high flow has a protective effect. Yet, why CCM lesions form only under low flow is still mysterious. This internship fits into a study on the role of unique sensors of blood flow, calcium channels which form pores across the membrane. Our work indicates for the first time that their dysfunction is triggering the formation of CCM. This internship will help unravel the abnormal signalling pathways activated by these channels. Thanks to Gingras lab’s world-renowned expertise in proteomics, the PhD student will reconstruct protein-protein interaction networks from the proteins that he has identified in the vicinity of these channels using in vivo proximity labelling by biotinylation (BioID). This project aims at identifying functional hubs targetable by FDA approved drugs to propose a cure for this disease that is sorely lacking today.

Faculty Supervisor:

Anne-Claude Gingras

Student:

Partner:

Université Grenoble Alpes

Discipline:

Life Sciences

Sector:

Education

University:

University of Toronto

Program: