Biology subjects

de Ceuninck van Capelle, C.

Publications and source records attributed to de Ceuninck van Capelle, C..

3 recordsLinked to original sources

bioRxiv2026

Novel protein networks in motile cilia from human epithelial cells revealed by cryo-ET and proteomics analysis of cilia from PCD patients

In our past study on human cilia from primary ciliary dyskinesia (PCD) patients using cryo-electron tomography and mass spectrometry, defects in the DNAH5 gene were proven to cause the loss of the entire outer dynein arm along with other proteins. This phenomenon was not observed in the unicellular green alga Chlamydomonas. In this study, we examined the loss of ciliary components caused by defects in various genes, based on proteomic and structural analyses of motile cilia from multiple PCD patients. The absence of single outer arm dynein genes causes a loss or significant decrease in other inner and outer arm dyneins. Interestingly, some patients with outer dynein defects show decreased intraflagellar transport (IFT) proteins, suggesting an influence of cargo components or assembly on transport. These phenomena were not observed in Chlamydomonas, suggesting a more complex mechanism of ciliogenesis in humans despite the high similarity in the final 3D architecture of the 9+2 axoneme. Defects in certain central pair proteins unexpectedly reduced components on the doublets as well. Our results demonstrate protein-protein interactions during stages of human motile ciliogenesis that are more complex than those in unicellular organisms.

cell biology↗

bioRxiv2025

Self-Supervised Missing Wedge Correction in Soft X-Ray Tomography: Towards Accurate Cellular Morphology and Volume Quantification

Soft X-Ray tomography (SXT) is a non-invasive bio-imaging technique that enables 3D imaging of cellular structures in large volume, with a unique resolution range that bridges the gap between fluorescence and transmission electron microscopy. However, a fundamental limitation, the missing wedge artefact caused by incomplete tilt-series acquisition, introduces systematic structural elongation in the reconstructed tomograms. This artifact compromises accurate quantitative biological analysis by overestimating cellular and organelle volumes. To overcome this persistent issue, we introduce a novel, self-supervised missing wedge correction model that learns key sine-wave patterns from existing SXT sinograms of the tilt series stacks. This model can be applied to recover the missing-angle region of the sinogram, reducing distortions and elongations in the reconstructed tomograms. We demonstrate a significant quantitative improvement in artifact removal, achieving faithful recovery of the spherical morphology of lipid droplets. We further applied this method to Plasmodium falciparum hemozoin crystals, a biomarker in antimalarial drug efficacy studies. Our model successfully reduced volume overestimation, achieving up to a 16% decrease in distorted volume. This level of precision is paramount for correctly interpreting the mode of action of antimalarial drugs.

cell biology↗

bioRxiv2025

Proteomic and structural comparison between cilia from primary ciliary dyskinesia patients with a DNAH5 defect

Primary ciliary dyskinesia (PCD) is a genetic disorder that affects the motile cilia in various organs, leading to recurrent respiratory infections, subfertility, and laterality abnormalities. Traditional diagnostic methods include high-speed video microscopy, immunofluorescence staining, electron microscopy, and genetic screening. However, how different disease-causing variants in the same PCD gene affect clinical presentation, as well as ciliary composition and structure, is not well understood. We investigated the effect of various mutations in DNAH5, an axonemal dynein heavy chain, using mass spectrometry and cryo-electron tomography. We demonstrated differences in the axonemal composition for patients with dnah5 mutations. Furthermore, we showed that reductions in some ciliary components are patient specific. Some of them, KIAA1430, CFAP97, and DTHD1, were not previously recognized as components of human respiratory motile cilia. Finally, we demonstrated that some differences in protein abundance between wild-type and PCD samples can be observed in the 96-nm repeated unit of the axoneme. Our results suggest that many axonemal components are affected in the DNAH5-defective samples. Additionally, our results highlight that disparate mutations have seemingly distinctive consequences for the axonemal composition.

cell biology↗