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Content Core of the Report ANNUAL REPORT 5 Content Core of the report. .............................................................................................................................. 2 2 Project objectives, work progress and achievements, project management ............................... 2 2.1 Project objectives for the period. ........................................................................................ 2 Recommendations from our Scientific Advisory Board ............................................................ 5 2.2 Work progress and achievements for the period. ............................................................... 7 WP1 ................................................................................................................................................ 7 WP2 .............................................................................................................................................. 23 WP3 .............................................................................................................................................. 30 WP4 .............................................................................................................................................. 38 WP5 .............................................................................................................................................. 47 WP6 .............................................................................................................................................. 61 WP7 ............................................................................................................................................ 113 WP8 ............................................................................................................................................ 122 WP9 ............................................................................................................................................ 128 WP10 .......................................................................................................................................... 137 2.3 Project management during the period. .......................................................................... 141 WP11 .......................................................................................................................................... 141 Consortium management tasks and achievements per scientific component: ........................ 141 Networking and Dissemination of the Results ........................................................................ 142 Overall Management of the Project ....................................................................................... 143 Financial management ........................................................................................................... 146 SYSCILIA annual report July 29, 2015 Page 1 ANNUAL REPORT 5 Core of the report. 2 Project objectives, work progress and achievements, project management 2.1 Project objectives for the period. WP1 - Mapping the ciliome O1.2 To identify supramolecular ciliary complexes using a combination of biochemical fractionation, immunoisolation, and proteomic analysis by quantitative mass spectrometry (MS) O1.5 Development of reagents and methods (antibodies, isolation protocols, ligands) for the study of specific complexes that emerged as candidates for disease markers O1.6 Identify protein interactions perturbed in specific ciliary diseases O1.7 Determine the distinct cellular/ciliary distribution of ciliome components WP2 - Central resource for data integration O2.1 To provide a robust, accessible and seamless system for storing, querying and updating data generated in the project O2.2 To provide systems biology read data to produce a model of the ciliary system and its relation to human pathology and disease O2.4 To integrate literature data with new finding that arise from experiments performed in the project O2.5 To analyse interactome data using socioaffinity and related concepts in order to derive accurate complex and interaction sets for feeding into WP3 and WP4 O2.6 To provide a forum for dissemination of data within the consortium and to the external scientific community WP3 - Construction, comparison and application of ciliary interactomes O3.1 Generate large scale systems biology ready interaction and reaction information O3.2 Assemble ciliary interactomes, functional networks, and pathways O3.3 Apply comparative evolutionary analysis to ciliary function and disease O3.4 Make molecular models and predictions for experimental testing SYSCILIA annual report July 29, 2015 Page 2 ANNUAL REPORT 5 WP4 - Integrative modelling and predictions of ciliary system behavior O4.1 To integrate outcome from all WPs into a network view of core ciliary processes O4.2 To partition this network into functional modules O4.3 To model and simulate modular ciliary processes with explanatory or predictive purposes WP5 - Assay systems to study functional ciliary modules O5.1 Quantifying ciliary transport O5.2 Assaying ciliary polarization O5.3 Measuring ciliary signaling WP6 - Assays to distort Ciliopathy-Associated Modules (CAMs) O6.1 Employ a semi high-throughput approach in mammalian cell culture and C. elegans to validate and further interrogate the roles of candidate CAM components (informed from WP1-4, 7 and 8) in cilium formation, maintenance, function, signaling and trafficking. O6.2 Establish and functionally assess animal models (zebrafish, Xenopus, mice) of individual candidate and known CAM components, employing systematic integrated and strategic methodologies (e.g. ciliary transport, polarity, signaling) developed in WP5 and elsewhere O6.3 Employ animal models (C. elegans, zebrafish, mice) to determine the genetic interrelationships between known/candidate components of individual and different CAMs WP7 - Systematic RNAi screens to distort and identify ciliopathy-associated modules O7.1 to distort the expression of known CAM genes in small- and medium-scale ciliome-wide screens O7.2 to confirm known and to identify novel CAM genes using large-scale genome-wide screens O7.3 integrate a high confidence list of validated known and novel CAM genes with other WPs to prioritize targets of interest O7.4 integrate RNAi screening data with outputs from other WPs and the central SYSCILIA resource to create a public database of validated CAM genes WP8 - Assessment of the involvement of the predicted ciliary molecular machines in the pathogenesis of ciliopathies O8.4 To integrate data on functional sequence variants and clinical information with information on CAMs to come to a system model for explaining and predicting phenotypes and their variability WP9 - Translational systems biology: ciliotherapeutics O9.3 Lead compound characterization SYSCILIA annual report July 29, 2015 Page 3 ANNUAL REPORT 5 WP10 - Dissemination and translation of knowledge O10.1 Coordinate training activities – workshops, webinars, etc. - inside the project to ensure more efficient collaborations. O10.2 Manage outreach in the form of external conferences, to ensure efficient dissemination of knowledge, impact and intellectual property to the external scientific community and relevant industries in Europe O10.3 Dissemination and outreach to the scientific community of SYSCILIA results, methods, standards and models O10.4 Translation of results and knowledge to industrial application O10.5 Monitor intellectual property rights (IPR) issues as they arise O10.6 Stipulate and update internal confidentiality agreements and external know-how agreements O10.8 Determine the appropriate time point for the dissemination of result from the consortium to the public O10.9 Assist in identifying of and liasing with industrial partners for the further exploitation of results WP11 - Overall Management of the Project O11.1 Proper conductance of the RTD specifically steering the conductance of the detailed implementation plan O11.2 Financial management O11.3 Managing seamless integration of all WP activities O11.4 Communication and progress monitoring, O11.5 Organisation of training activities, committee meetings, retreats O11.6 Management and delivery of progress reports to the commission O11.7 Management of Conflict resolution O11.8 Quality assurance and control O11.9 Risk Management O11.10 Dissemination and translation of results SYSCILIA annual report July 29, 2015 Page 4 ANNUAL REPORT 5 Recommendations from our Scientific Advisory Board April 23, 2015, Pozzuoli, Italy Scientific Advisory Board (SAB) on the 2015 meeting of the SYSCILIA consortium SAB members present: Alfred Wittinghofer, Martijn H. Breuning and Erich E. Wanker The fifth annual meeting of the SYSCILIA consortium was held from 22-24 April at the TIGEM in Pozzuoli, Italy. It was the fourth meeting at which SAB members were present. Once again we were impressed with the constructive atmosphere, the enormous enthusiasm of all participants, the readiness to share ideas, data and tools, and the willingness to collaborate closely in order to realise project goals. After having experienced several EU-funded projects, the SAB members find SYSCILIA exceptional. The consortium is highly integrated and clearly follows a common research goal. In previous meetings, research plans and future experiments were presented. Now, in this final meeting many researchers reported very interesting results at a very mature stage. This includes the mapping of the ciliome, the sequencing of patient DNAs, and the
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