PhD Project ESR11
Impact of small molecules and peptides on Tau-MT interaction and tau aggregation in primary peripheral neurons and models of Alzheimer’s and Parkinson’s disease.
SUPERVISORS
Prof. Roland Brandt, University of Osnabrück
Dr. Fernando Diaz, Centro de Investigaciones Biológicas and Universidad Internacional Menéndez Pelayo, Santander, Spain (secondment)
INVOLVED UNIVERSITIES
INVOLED COMPANY
Indena, Milan, Italy
PhD COURSES
Biosciences (UOS)
Science and technology (UIMP)
OBJECTIVES
- Study of the efficacy of potential compounds modulating Tau/Tub interaction and Tau aggregation in vitro.
- Establishing the use of primary cortical and peripheral neurons from Tau KO mice for the determination of Tau-MT interaction and Tau aggregation after virus-mediated expression of exogenous physiological and pathological Tau constructs by quantitative live cell imaging in authentic axons and dendrites.
- Determination of the effect of novel cell-permeable compounds on the interaction between Tau and MTs in primary cortical and peripheral mouse neurons using the approach established in (2).
- Analysis of the effect of potential modulating compounds as determined in (3) on MT-Tau interaction in ex vivo models of Alzheimer’s and Parkinson’s disease.
DESCRIPTION OF THE PROJECT
The Early Stage Researcher (ESR) will identify and characterize small molecules and peptides that influence Tau-MT interaction and Tau aggregation as potential lead structure for modulating Tau-dependent toxicity in Alzheimer’s and Parkinson’s 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. 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 Consejo Superior de Investigaciones Científicas (CSIC) (https://www.csic.es/) under the supervision of Prof. Fernando Diaz. The research will involve secondments to the CSIC (Determination of the structural influence of Tau and small molecules on MTs using fibre diffraction and cryo-electron microscopy) and the company INDENA (quality assurance and management) (http://www.indena.com/), Italy. The selected candidate will participate in the network’s training activities and work placements in the laboratories of the participating academic and industrial partners.