Sigrid Milles

Host institution: National Centre for Scientific Research (CNRS)

Laboratory: IRIG

Call for Projects: Starting (LS1)

Project name: MultiMotif – Motif repeats in intrinsically disordered regions of the clathrin mediated endocytosis pathway

Amount: 1.59 M€

Description:

Linear motifs are short sequence stretches that occur in intrinsically disordered protein regions (IDRs) lacking stable secondary and tertiary structure, and mediate vital interactions within various biological systems. An exemplary system for the presence of IDRs and a high concentration of linear motifs is the clathrin mediated endocytosis machinery of the eukaryotic cell, where a complex interaction network of IDR-rich adaptor proteins enables both protein and lipid interactions. The molecular mechanism of such interactions, especially when multiple motifs act in concert, is however only poorly understood particularly since the dynamic and flexible nature of IDRs makes them a very difficult object to study. I aim to develop an integrative approach based on single molecule fluorescence and NMR spectroscopies to characterize the molecular principles of IDRs in clathrin mediated endocytosis. A systematic analysis of IDRs with different types of motifs and various interaction partners will not only shed light on the molecular functions of linear motifs within endocytosis, but also on how multiplicities of linear motifs may work in various biological processes in general. In vitro structural studies will be connected with single molecule imaging to relate molecular conformation with function within the cell.