Postdoc Parkinson’s disease (PD) IPSC model systems

Parkinson’s disease (PD) encompasses a spectrum of motor and cognitive/psychiatric symptoms. Dementia may occur early, before parkinsonism, as in Dementia with Lewy bodies (DLB), or later in the course of the disease (PDD). Mutations in GBA1 and LRRK2 are the most common genetic risk factors. Up to 80% of cases are genetically sporadic. Although many upstream pathways may cause PD, the downstream consequence will be an end-stage α-synucleinopathy in most cases.

To overcome the heterogeneity dilemma that hampers drug development, here, we implemented a translational approach that integrates within-subject clinical and pathological information with morphological and molecular knowledge of induced pluripotent stem cells (iPSC) of PD(D)/DLB patients to identify molecular profiles and drug targets.

We will collect skin biopsies from PD patients of whom brain pathological confirmation is available. In parallel, we prospectively collect skin biopsies from well-phenotyped Parkinson patients (ProPARK cohort). We generate well-defined iPSC. Using advanced genomics and proteomics we aim to identify molecular profiles in these iPSC lines and brains. This will eventually help us to identify and validate druggable targets for molecular subtypes in PD(D) using a disease subtype classification based on pathology or dysregulated cell biology.

WP1. To generate well-defined iPSC and differentiate into neural cells that can be used for FTD and PD(D)/DLB subtype-tailored compound testing.

WP2. To identify molecular profiles and novel drug targets in iPSC and human post-mortem brain tissue from well-characterized PD(D) patients using advanced genomic, proteomic and proteomic techniques.

WP3. To aid identification/validation of druggable targets and biomarkers in post-mortem brain tissues and iPSC of FTD and PD(D)/DLB patients using a disease subtype classification based on pathology or dysregulated cell biology.

Techniques: neuropathology neurodegenerative disorders, fibroblast and IPSC cell culture, protoeomics, genomics, cellomics and high-end 3D microscopy.

We are looking for a candidate who has experience with the characterisation of IPSC-derived dopaminergic or cortical neurons.

• You have a recent PhD degree in Biomedical Science, Molecular/Cellular Biology, Neuroscience, or a related field with a keen interest in molecular and cellular mechanisms of neurodegenerative movement disorders.
• Experience with cell culture and molecular biology methods, as well as bioinformatics (R, etc.) are required;
• Programming skills in different languages (Matlab, R) and experience with analysis of proteomics data is essential.
• You are highly motivated, creative and willing to work with human postmortem brain tissue and Parkinson model systems.
• Within this project most communication will be in English, so fluency in English and excellent communication and organizational skills are essential.
• You are communicative, well organized, independent and willing to supervise PhD and Msc students.

As postdoc, you will work in the section Clinical Neuroanatomy and Biobanking (CNAB) at the department of Anatomy and Neurosciences, Amsterdam UMC, location VUmc, Amsterdam. Our mission is to unravel cellular disease mechanisms in Parkinson's and related disorders in order to develop early diagnostics tools and identify drug targets for novel treatment paradigms.

Clinical Neuroanatomy & Biobanking – Anatomie en Neurowetenschappen (anatomy-neurosciences.com)
You will contribute to the program Neurodegeneration and Amsterdam Parkinson and Movement Disorder Centre.

Neurodegeneration (amsterdamumc.org)