ESR1

The molecular basis of ciliopathy causing mutations in the ciliary assembly machinery


To construct and maintain a functional cilium, cells rely on the intraflagellar transport (IFT) machinery consisting of about 30 IFT proteins. An increasing number of mutations in ciliopathy patients maps to genes encoding the IFT machinery. In most cases, the molecular basis for why mutations cause defects in cilium assembly, function and ciliary signalling pathways is unknown. Understanding defects at the protein level in ciliopathy mutants will be important to provide a molecular basis of ciliopathy diseases. The PhD student associated with ESR1 will purify wild-type and ciliopathy causing mutants of IFT proteins/complexes and study their structure, stability and interaction network. The impact of mutations on protein complex assembly and cargo interactions will also be studied. High-resolution structures will be determined by X-ray crystallography and cryo-EM methods (in collaboration with PO2-MPI-CBG). Together with partner 2 (P2-UCPH), the functional importance of structure-guided mutations will be probed using cell-based assays to provide a complete molecular basis of IFT complex function in health and disease.

Partner: Aarhus University, Denmark

Supervisor: dr. E. Lorentzen