Project number 3

Structural biology of Alzheimer’s disease

Our laboratories are deeply interested in understanding the molecular basis of Alzheimer’s disease. The PhD project will be focused on the disease mechanism, trying to further elucidate how mutations in the y-secretase complex cause early onset Alzheimer’s disease. γ-Secretase proteolytic complexes cleave the amyloid precursor protein and produce amyloid-beta (A-beta) peptides of which accumulation is one of the hallmark of Alzheimer’s disease. γ-Secretases are fascinating intramembrane proteases, unravelling their molecular mechanisms will be the crucial step on the path to develop efficient and safe medication for Alzheimer’s disease. 
The goal of the PhD project will be to reveal the molecular mechanism of γ -secretase complexes at the atomic level using combination of biochemistry, high-resolution single particle cryo-EM and molecular biology.  The candidate will investigate mutations associated with disease and explore their underlying mechanisms to move towards rational development of drugs against Alzheimer’s disease.
The biochemical and functional part of the project will be conducted in the Switch Lab at the University of Leuven. The structural work will be performed in the Laboratory of Prof. Rouslan Efremov at the Structural Biology Research Center of Free University of Brussels (VUB), who is internationally respected for his research in structural biology of membrane bound receptors. A newly created cryo-EM facility including state-of-the-art cryogenic electron microscope equipped with direct electron detector for high-resolution single particle analysis will be available at VUB.

Keywords
single particle cryo-EM, Alzheimer’s disease, gamma-secretase, neurodegeneration, drug development

Supervisors
Rouslan Efremov, VIB Structural Biology Research Center, VUB, Brussels
Joost Schymkowitz/Frederic Rousseau, VIB SWITCH Lab, KU Leuven, Leuven