PhD Project ESR10
Impact of small molecules on neuronal microtubule (MT) assembly and MT dynamics by quantitative live cell imaging of model neurons.
SUPERVISORS
Prof. Roland Brandt, University of Osnabrück
Prof. Graziella Cappelletti, University of Milan (secondment)
INVOLVED UNIVERSITIES
INVOLED COMPANY
PhD COURSES
Molecular and Cellular Biology (UNIMI)
Biosciences (UOS)
OBJECTIVES
- Validation of the modelling and quantitative live cell imaging approach to determine MT-assembly and MT-dynamics in model neurons by using known compounds (epothilone, discodermolide, nocodazole), which interfere with MT polymerization.
- Determination of the effect of novel cell-permeable compounds on MT dynamics using the validated approach from (1).
- Analysis of the effect of potential modulating compounds as determined in (2) on MT-dependent spine loss, dendritic simplification and metabolic activities in ex vivo models of Alzheimer’s and Parkinson’s disease.
DESCRIPTION OF THE PROJECT
The Early Stage Researcher (ESR) will identify and characterize known and novel small molecules that affect neuronal MT assembly as potential lead structure for modulating MT dynamics in disease models and patients. The project will involve state-of-the-art single molecule tracking and live cell imaging approaches using model neurons and ex vivo models (for references see: Niewidok et al. (2018) J. Cell Biol. 217:1303–1318; Gauthier-Kemper et al. (2018) J. Biol. Chem. 293:8065-8076; Brandt and Bakota (2017) J. Neurochem. 143:409-417). The ESR will be enrolled at the University of Osnabrück (https://www.uni-osnabrueck.de/en/home/) under the supervision of Prof. Roland Brandt and will be awarded a Double Doctorate degree with the University of Milan (https://www.unimi.it/en/node/2) under the supervision of Prof. Graziella Cappelletti. The research will involve secondments to the University of Milan (to explore cellular neurodegeneration models of Parkinson’s disease) and the company IONOVATION GmbH (electrophysiological measurements and membrane biophysics (https://www.ionovation.com/), Germany. The selected candidate will participate in the network’s training activities and work placements in the laboratories of the participating academic and industrial partners.