Graphical abstract.
Yale researchers David Breslow and Mustafa Khokha have developed a novel CRISPR screening technology that provides unprecedented insights into cilia, tiny hair-like cellular structures whose defects are linked to a range of paediatric developmental disorders. Their work, published in the journal Developmental Cell , merges CRISPR gene editing, automated microscopy, AI image analysis, and a UV-based method to mark individual cells, enabling the scanning of millions of cells to identify mutations that alter cilia. This approach revealed hundreds of genes that control cilia formation and function and led to the discovery of a microprotein essential for both cilia development and normal embryonic growth in frog embryos, suggesting potential relevance to human genetic diseases.
The technology is designed to be accessible, allowing researchers to study cellular processes in fine detail without specialised expertise in microscopy or software. Originally connected through Yale’s Cilia Group, Breslow and Khokha focused their collaboration on understanding how ciliary mutations drive disorders affecting key bodily systems such as the skeleton, heart, and brain. The platform can also be adapted to study other organelles or disease mechanisms, accelerating gene discovery for developmental disorders and broader cellular research.
Breslow emphasises that this tool will deepen understanding of cilia’s role in disease and can be deployed widely in diverse research applications.
Image Credit: Developmental Cell (2025). DOI: 10.1016/j.devcel.2025.10.015 (Phys.org)
