PhD Project ESR8
Dissecting the interaction of α-Synuclein with tubulin/microtubules.
SUPERVISORS
Prof. Graziella Cappelletti, University of Milan
Prof. Roland Brandt, University of Osnabrück (secondment)
INVOLVED UNIVERSITIES
INVOLED COMPANY
PhD COURSES
Molecular and Cellular Biology (UNIMI)
Biosciences (UOS)
OBJECTIVES
The aim of the project is to investigate in detail the interaction of a-Synuclein with tubulin and microtubules and to disclose the role of such an interaction in molecular mechanisms of neurodegeneration.
DESCRIPTION OF THE PROJECT
The Early Stage researcher (ESR) will first investigate the interaction of a-Synuclein with tubulin and their aggregation properties in cell-free system. She/he will purify the proteins and carry out multiple experimental analyses including tubulin assembly kinetics, thermophoresis, NMR, cryo Electron Microscopy, and Real Time Quacking Induced Convertion (RT-QuIC). Then, the ESR will move to investigate i) microtubule assembly and dynamics, and ii) a-Synuclein aggregation in neuronal cell cultures. She/he will perform biochemical and morphological studies in cultures overexpressing wild-type and pathological variants of a -Synuclein including cell fractionation and Western blotting, confocal and super-resolution microscopy, and Proximity Ligation Assays. Finally, she/he will check in cell-free system and in neuronal cell cultures for the efficacy of those compounds and peptidomimetics that will be discovered by the TubInTrain network and will be indicated as the most promising in modulating a-Synuclein/tubulin interaction and a- Synuclein aggregation.
The ESR will be enrolled by the University of Milan (https://www.unimi.it/) under the supervision of Prof. Graziella Cappelletti and will be awarded a Double Doctorate degree in co-tutelle with the University of Osnabrueck (https://www.uni-osnabrueck.de), under the supervision of Prof. Roland Brandt.
The research will involve 12 months secondment to the University of Osnabrueck (analysis the impact of a-Synuclein on microtubules in neurons by using the quantitative live cell imaging approach developed by R. Brandt) and 3 months secondment to Biorep,Milan, Italy (http://www.biorep.it/en).
The selected candidate will participate in the network’s training activities and work placements in the laboratories of the participating academic and industrial partners.