Ph.D. Student for experimental and clinical neuropathology: Alzheimer's disease
Posted 11 Jul 2017
The Laboratory of Neuropathology focuses on the pathogenesis of neurodegenerative disorders. The main focus is on Alzheimer’s disease.
Funding will be received for the next four years from an FWO Odysseus grant for a project focusing on the composition of protein aggregates in Alzheimer’s disease and other neurodegenerative disorders throughout the evolution of the disease and their maturation steps over time. To identify such steps in protein aggregate maturation human brain samples will be analyzed biochemically and neuropathologically. The pathogenic potential of such aggregates will be tested in animal models of the disease.
The diagnostic impact of such changes will be established in tracer binding studies with PET ligands.
These observations will be used to improve detection of preclinical Alzheimer’s disease patients and to identify novel targets for disease treatment.
Project: Alzheimer's disease is histopathologically characterized by the deposition of the Aβ protein in senile plaques and by the generation of neurofibrillary tangles composed of abnormal phosphorylated tau protein. A third protein that is found to be aggregated in the Alzheimer’s disease brain is TDP43. Recently, it has been shown that the composition of Aβ protein aggregates changes throughout the pathogenesis of Alzheimer's disease from aggregates consisting mainly of non-modified Aβ peptides into aggregates that contain numerous modified forms of Aβ.
This project will address the hypothesis that other proteins such as TDP43 aggregates in AD show similar signs of aggregate maturation as Aβ. It will test whether these aggregates have a cross-seeding capacity in mouse models for Aβ and tau-pathology, and intends to clarify at which stage of the disease (biochemical stage of aggregation) protein aggregates are capable of triggering or enhancing disease progression just by their presence. That could define at which stage of the disease it will convert into a self-propagating disorder. This point in the disease pathogenesis may be an ideal point to interfere pharmacologically.
Offer: The position is for four years (financed by FWO). It includes promotion of the Ph.D. thesis to be written within the term, participation in an individually shaped Ph.D. program, and presentation of valuable findings at international conferences.
- Animal experiments with transgenic mice (stereotactic injections into the brain).
- Biochemical protein analysis of human and mouse brain samples (western blot analyses, SDS-PAGE, immunoprecipitation, mass spectrometry).
- Pathological analysis of mouse and human brain tissue.
The candidate should be experienced in the following techniques:
- Sample preparation for biochemical analysis.
- Western blot analysis.
- PCR analysis.
- Mass spectrometry (not mandatory).
- Master's degree according to EU standards.
- FELASA B certificate for carrying out animal experiments (or follow the FELASA B course within the first three months).