Systems biology approach reveals new insights in disease mechanisms and functions related to the cell’s antenna
As part of an international team of researchers, RIMLS scientists have systematically identified and mapped new protein components related to cilia (dys)function.
Cilia project from the surface of most cells in our body, acting either as the cell’s fluid propellors (motile cilia), or as the cell’s antenna for signal reception and transmission (primary, immotile cilia). Improper cilia development due to genetic defects can result in a range of hereditary disorders called ciliopathies. Around 1 in 1000 people suffer from a ciliopathy. Common complications of ciliopathies are kidney failure, a significant cause of childhood disease and death, hearing loss, blindness, skeletal abnormalities, and even cancer, occurring often in combinations.
The study, published in Nature Communications, gives detailed insights into the connections made by over 1300 proteins as part of ciliary protein complexes, networks or signaling pathways. Using these datasets and new bioinformatic algorithms to model them, the researchers defined new molecular machines that determine proper functioning of the cilia. Dysfunction of these machines resulting from genetic mutations may result in defective cilia and cause ciliopathies.
RIMLS researcher Ronald Roepman, professor of Molecular Biology of Ciliopathies at the Radboudumc, Dept. of Human Genetics, theme Renal disorders was one of the leaders of this collaborative study: “By combining different scientific expertise and sharing research data between 18 research groups involved in SYSCILIA, we undertook a systems biology approach to scrutinize this biologically isolated system that a cilium is. Thereby we were able to develop computer models that predict which proteins work together in cilium function. In addition we were able to classify known inherited disorders, like the 3M syndrome, as ciliopathies, which is essential knowledge for translational research towards therapies.”
Reference: An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nature Communications.
(Photo: Jeroen van Reeuwijk (Dept. of Human Genetics, Radboudumc and RIMLS), shared first author on the paper)
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