Compartmentalized ciliary proteome analysis

Cilia are highly compartmentalized structures. These compartments, namely basal body, transition zone, axoneme and tip, are characterized by a distinct protein composition that is dynamically altered, depending on the ciliary state. To date, a comprehensive definition of the compartmentalized proteome and the changes induced by disease is lacking. By employing and adapting state of the art proximity-labelling technologies (TurboID or APEX), this project aims at defining the protein composition of the ciliary compartments.  To this end, endogenously tagged cell lines with proximity-labelling tags on specific marker proteins will be developed to dissect the whole ciliary proteome, the ciliary tip proteome as well as the basal body proteome as well as the transition zone. The protein composition of these compartments as well as its alterations upon knock-out of ciliopathy associated proteins or knock-in of disease-associated mutant (i.e. LCA5, CEP290, RPGRIP1L) will be quantitatively analysed by mass spectrometry. Data analysis and integration with pre-existing data like the ciliary landscape will lead to a detailed understanding of the ciliary mechanisms, leading to disease.

Fellow profile: Master degree, including written master thesis, in Life Science field. This project is very suitable for students with a keen interest in developmental cell biology who are motivated to develop AI/ML-based data integration and molecular modelling skills.