Chromatinopathies (CPs) are Mendelian disorders caused by mutations in chromatin regulators and often present with neurodevelopmental delay and intellectual disability. While many CPs have distinct clinical features, subsets show overlapping phenotypes and cluster into molecular groups. We hypothesize that within these subgroups, different CPs converge on common defects in chromatin state, 3D genome organization, and transcriptional programs, revealing shared biological vulnerabilities and potential future therapeutic entry points.
This PhD project is jointly supervised by Dr. Renske Oegema (clinical geneticist) and Dr. Peter Krijger (molecular biologist). The two research PIs combine expertise in clinical genetics and access to well-characterized patient cohorts with mechanistic gene regulation and functional genomics. You will model patient variants in chromatin regulators using genome editing and cellular disease models and apply chromatin and 3D genome profiling to determine how these variants disrupt chromatin state, genome folding, and transcription.
Your research will focus on:- Identifying chromatin regulators and pathways recurrently affected in developmental and neuropediatric disorders using patient-derived genetics and clinical data.
- Defining the molecular consequences of disruption on chromatin organization, 3D genome folding, and gene expression.
- Establishing unbiased screens to functionally test chromatin-protein variants in parallel.
- Linking molecular changes to disease-relevant cellular phenotypes to support diagnosis and lay the groundwork for future therapeutic studies.
€35000 - €45000 monthly