In both Alzheimer’s disease (AD) and glioma, many molecular processes are disrupted, but the precise underlying mechanisms remain largely unknown. Recent advances in proteomic techniques have made it possible to study molecular complexity of these disorders in more detail and have revealed that distinct disease subtypes may exist in these disorders that each require subtype-specific therapy.

The aim of this project is to further understand the underlying mechanisms of subtype-specific molecular alterations in CSF by investigating protein and RNA alterations in extracellular vesicles (EVs). EVs are released from brain cells and their content reflects not only their cellular origin but also the biological (disease) state of the cells in question. In parallel, we will extract and analyze EVs released by brain cells and tumor tissues derived from the very same patients, allowing for the first time to link CSF molecular profiles to cell type- and tissue-specific pathophysiological mechanisms.

You will develop, in a team with world experts, novel techniques for EV extraction from CSF of AD patients and of patients with glioma tumors, and perform proteomic and transcriptomic profiling of EVs. With this data you will be able to further our knowledge of the common and unique aspects of these brain disorders to better understand specific pathogenic mechanisms. The project will thus significantly contribute to new insights into the underlying disease mechanisms in AD and glioma, which may translate directly into biomarkers that could have use in the clinic.

PhD position 1 (patient CSF) You will be isolating and characterizing EV populations from CSF derived from AD and glioma patients. You will analyze EV content using proteomics and transcriptomics approaches. You will use advanced bioinformatics approaches to discover AD and glioma subtypes as well as subtype-specific disease mechanisms based on EV content. You will closely collaborate with PhD student 2 in this project to reveal cell type-specific disease mechanisms based on EV content. You will explore commonalities between AD and glioma molecular and cellular pathologies based on EV content.

PhD position 2 (iPSC models) You will be isolating and characterizing EV populations from iPSC-derived brain cells and surgically resected tumor tissues from AD and glioma patients. You will analyze EV content using proteomics and transcriptomics approaches. You will use advanced bioinformatics approaches to discover cell-type specific EV profiles in relation to disease subtypes. You will study cell-type specific disease mechanisms in iPSC-derived models for AD and glioma. You will closely collaborate with PhD student 1 in this project to correlate cell type-specific EV profiles with CSF-derived EV profiles from patients. You will explore commonalities between AD and glioma molecular and cellular pathologies based on EV content.

• MSc degree in biomedical science/neuroscience;
• Background in molecular and cellular neuroscience;
• Experience with -omics techniques and data analysis;
• Experience with iPSC culture (PhD position 2);
• Affinity with translational research;
• Creative and curious, able to link scientific discoveries and formulate new concepts;
• Excellent scientific writing skills.

• A flying start to your career in scientific research.
• Plenty of room for your drive to shape tomorrow's healthcare.
• Working on large-scale and in-house research, with motivated colleagues from all over the world.
• A contract for 12 months (extension possible, subject to funding).
• Salary scale OIO: € 3.017 to € 3.824 gross based on full-time employment (depending on education and experience) and a year-end bonus of 8.3%. Calculate your net salary here.
• Holiday hours: 186,4 per year for fulltime and a possibility to save additional hours.
• Pension accrual with BeFrank, a modern, comprehensible and fairly priced pension.
• Now still a (partial) reimbursement of your public transport travel costs. From 1 October, for >7 km each way, 100% public transport reimbursement and, for private transport, €0.18 per km up to a maximum of 40 km each way.
• Do you prefer walking or cycling? Take advantage of our good bike scheme. And from 1 October, you will receive a reimbursement of €0.18 per km.

Watch this video with more information about joining Amsterdam UMC Research BV.

Amsterdam UMC

Alzheimer Center Amsterdam is an (inter)national leading center in the field of top clinical care and high-quality scientific research into dementia. The Alzheimer Center is a stimulating workplace with more than 100 employees where an informal atmosphere goes hand in hand with ambitions and attention to personal development.

The department of Molecular and Cellular Neurobioology is part of the Center for Neurogenomics and Cognitive Research (CNCR). CNCR is the operational name of the Department of Neuroscience at the Faculty of Science of the Vrije Universiteit Amsterdam. CNCR runs interdisciplinary research programs from genes to behavior, combining rodent and human studies, and coordinates multiple national and international research consortia, providing a diverse and stimulating research environment for many PhD students and postdocs. Our PhD candidates participate in the Graduate School Neurosciences Amsterdam Rotterdam.