PhD Project ESR4


Development of small molecules to modulate MT stability.

SUPERVISORS

Dr. Andrea Prota, University of Basel and Paul Scherrer Institute, Basel

Dr. Stefano Pieraccini, University of Milan (secondment)

INVOLVED UNIVERSITIES

INVOLED COMPANY

PhD COURSES

Industrial Chemistry (UNIMI)
Biochemistry (UBas)

OBJECTIVES

1)Assay development to determine tubulin binding kinetics of new compounds prepared by ESR3.
2) Evaluation of newly synthesized compounds to define their tubulin binding kinetics and their activity on tubulin assembly.
3) High-resolution structure determination of tubulin-compound/tubulin-a-synuclein complexes by X-ray crystallography and/or cryo-EM.

DESCRIPTION OF THE PROJECT 

The Early Stage researcher (ESR) will develop a wave-guided interferometry-based assay to determine the tubulin binding kinetics of the synthesized molecules. The tubulin-ligand interactions and their activity on tubulin assembly will be further characterized by selected biochemical and biophysical methods. In coordination with ESR8, the a-synuclein peptide-boundaries for tubulin interaction will be determined and optimized for structural analysis. The high-resolution structures of the most promising tubulin-ligand/tubulin-a-syn complexes will be determinded by X-ray crystallography and/or cryo-EM. The ESR will obtain state-of-the-art training in crystallization of tubulin-ligand complexes, data collection at synchrotron and structure determination techniques including cryo-EM.

The ESR will be employed by the Paul Scherrer Institute (https://www.psi.ch) under the supervision of Dr. Andrea E. Prota and enrolled at the University of Basel (https://www.unibas.ch), under the supervision of Prof. Michel O. Steinmetz. A Double Doctorate degree will be awarded in co-tutelle with the University of Milano (https://www.unimi.it), under the supervision of Prof. Stefano Pieraccini.

The research will involve secondments at the University of Milan (12 months, https://www.unimi.it; molecular modelling of compound derivatives) and LeadXPro (3 months, https://leadxpro.ch), Switzerland.

The selected candidate will participate in the network’s training activities and work placements in the laboratories of the participating academic and industrial partners.

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