Postdoctoral Researcher in Alzheimer’s Drug Discovery

APOE is the strongest genetic risk factor for Alzheimer’s disease. People carrying the APOE4 variant have a substantially increased risk of developing the disease. In this project, you will work on a novel therapeutic strategy aimed at blocking the uptake of APOE4 and reducing its toxic effects in the brain.

You will develop a biochemical assay to study the interaction between APOE4 and its receptor and apply this assay in different drug screening approaches, including fragment screening and DNA-encoded library (DEL) screening. Candidate compounds will subsequently be validated using biophysical assays and further optimized for preclinical development.

The project is embedded within a larger drug discovery program focused on neurodegenerative diseases and is carried out at the Candidate Center at Amsterdam UMC. You will closely collaborate with the group of prof. dr. Iwan de Esch at the AIMMS institute of VU Amsterdam, where complementary expertise in medicinal chemistry and structure-based modelling is available.

As a postdoctoral researcher, you will contribute to the development of novel therapeutic compounds targeting APOE-related disease mechanisms in Alzheimer’s disease. You combine biochemical assay development with translational drug discovery research in a multidisciplinary collaboration.

Your work includes:

• establishing biochemical assays that model APOE-receptor interactions using recombinant proteins;
• performing fragment screening and DEL screening to identify compounds that disrupt APOE-receptor binding;
• developing and applying orthogonal biophysical assays to validate candidate compounds;
• contributing to the preclinical characterization and optimization of identified compounds;
• collaborating with researchers in biochemistry, medicinal chemistry, and neurodegeneration research across Amsterdam UMC and VU Amsterdam.

In addition, you will contribute to scientific publications, present your work at meetings and conferences, and actively participate in collaborative research activities within the consortium.

We are looking for an independent and motivated researcher with a strong interest in translational neuroscience and drug discovery.

You have:

• a PhD degree, or are close to completing a PhD, in biochemistry, medicinal chemistry, drug development, pharmaceutical sciences, or a related field;
• experience with biochemical assays and preferably affinity with in vitro drug screening approaches;
• knowledge of, or experience with, high-throughput screening technologies and protein-protein interaction assays;
• strong analytical skills and the ability to work independently within multidisciplinary collaborations;
• excellent written and spoken English communication skills.

Experience with fragment-based drug discovery, DEL screening, or medicinal chemistry approaches is considered an advantage.