Patients affected by hereditary ciliopathies show variable disease conditions including blindness and/or kidney cysts and mental retardation. The common defect in ciliopathies is a malfunction of the cilium. The cilium is a cellular organelle that projects from the surface of almost every polarized cell in the human body and serves as an antenna for sensing, communicating or for mechanical bridging. Cilia are essential to see, hear, smell, reproduce and breath.
The study was published in Nature Communications on May 13 2016. The team from Germany, Netherlands, United Kingdom, Italy, Ireland, USA and France working in the EU project SYSCILIA (www.Syscilia.org) for the first time comprehensively analysed the ciliary protein network. By integrating and analyzing data from multiple disciplines, the protein network was transformed into an information-rich landscape.
Lead researchers were Karsten Boldt and Marius Ueffing from Tuebingen, Ronald Roepman and Jeroen van Reeuwijk from Nijmegen, Rob Russell and Qianhao Lu from Heidelberg and Konstantinos Koutroumpas from Paris. Karsten Boldt and colleagues built on their previous study from 2011 that had pioneered the identification of altered protein complexes in a single blindness gene. They showed that LCA5 leads to childhood blindness in Leber Congenital Amaurosis by disabling the protein Lebercilin to participate in protein complexes in the cilium. For the current study of 2016, Boldt and co-workers decided to widen their approach in the EU consortium SYSCILIA. In the consortium, they present a comprehensive ciliary landscape. Karsten Boldt: “Only by combining unique expertise from different fields, we could generate a great resource for basic cilia biology and for understanding ciliopathies. We think that this will aid researchers to generate and test novel hypothesis to better understand cilia function in health and disease.“
Boldt et al analysed the complexes of 217 proteins known or suspected to possess a cilia-related function and integrated cell biological and medical sequencing data. The scale and depth of the study could only be achieved by the development of novel experimental tools and data analysis algorithms. The impact of the study derives from the fact that it bridges the gap between protein networks, basic science and human genetics.
Marius Ueffing: “SYSCILIA assembled a multidisciplinary team of excellent researchers from all over Europe. Close collaboration and stimulating discussions enabled us to do something unique, moving systems biology closer to medicine.”
Details of the publication
An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Boldt K, van Reeuwijk J, Lu Q, Koutroumpas K, Nguyen TM, Texier Y, van Beersum SE, Horn N, Willer JR, Mans DA, Dougherty G, Lamers IJ, Coene KL, Arts HH, Betts MJ, Beyer T, Bolat E, Gloeckner CJ, Haidari K, Hetterschijt L, Iaconis D, Jenkins D, Klose F, Knapp B, Latour B, Letteboer SJ, Marcelis CL, Mitic D, Morleo M, Oud MM, Riemersma M, Rix S, Terhal PA, Toedt G, van Dam TJ, de Vrieze E, Wissinger Y, Wu KM, Apic G, Beales PL, Blacque OE, Gibson TJ, Huynen MA, Katsanis N, Kremer H, Omran H, van Wijk E, Wolfrum U, Kepes F, Davis EE, Franco B, Giles RH, Ueffing M, Russell RB, Roepman R; UK10K Rare Diseases Group. Nat Commun. 2016 May 13;7:11491. doi: 10.1038/ncomms11491.