We map the protein networks that build and regulate the primary cilium. Combining interaction screens (yeast two-hybrid, tandem affinity purification, BioID proximity labelling), affinity proteomics and systems biology, we and our partners have generated the first ciliary protein landscape. We now resolve these networks in space and time. With Microscoop Mint spatial optoproteomics, we capture proteins from microscopy-defined subciliary regions in cells and tissue, and we use machine learning to integrate data across molecular and cellular scales.
We study how ciliary dysfunction causes disease, with a focus on the retina and the kidney. In photoreceptors, we investigate the connecting cilium and the bulge region at its tip, where outer segment discs form, and how proteins such as lebercilin (LCA5) and PCARE shape this compartment. In close collaboration with the Akhmanova lab (Utrecht University), whose in vitro reconstitution assays reveal how ciliary tip proteins control microtubule growth, we explore how disease variants disturb this process. We also study how impaired autophagy contributes to retinal degeneration. In the kidney, we investigate how ciliary defects drive cyst formation in nephronophthisis and polycystic kidney disease. Our models include patient-derived retinal and kidney organoids, zebrafish and mice.
We translate these insights into better diagnosis and treatment of ciliopathies. Building on the ciliopathy genes we have identified, including LCA5, RPGRIP1L, ARMC9 and TOGARAM1, we work with clinical geneticists to find the genetic cause in patients who remain undiagnosed. We also develop cellular cilium phenotyping assays that functionally validate genetic diagnoses and classify patients by their cilium phenotype. In parallel, we explore therapeutic strategies with our partners: AAV gene augmentation, CRISPR-Cas9 correction and small molecules that alleviate photoreceptor cilia defects. Within international consortia, we search for druggable targets for renal ciliopathies.
Welcome to Research
We study how defects in the primary cilium, the cell's sensory antenna, cause ciliopathies, from photoreceptor degeneration to polycystic kidney disease. We map its protein networks to find targets for new treatments.
Roepman Lab
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