Main task in COSYN: Patrick Sullivan was the coordinator of COSYN, and lead of WP1 and co-lead of WP2. He is a psychiatric geneticist who is involved in multiple large-scale genomics studies. He integrated the efforts of COSYN investigators and provided context with respect to the rest of the field.
PI: Professor Thomas Bourgeron, firstname.lastname@example.org
Department: Head of structure: Human Genetic and Cognitive Funtions; Center for Translational Science, research.pasteur.fr/en/member/thomas-bourgeron/
Main task in COSYN: The Bougeron group in collaboration with Prof. Delorme from the Robert Debré Hospital in Paris identified patients with autism carrying deleterious mutations in synaptic genes. The mutations were identified though whole genome/exome sequencing in a cohort of more than 3000 patients. The patients were explored at the clinical level including brain MRI and EEG. Whenever possible, the patients and their relatives were also sampled for generating induced pluripotent stem cells (iPSC) by partner Brustle. These iPSCs were then used to derive neurons from and studied using cellular assays by partners Brose, Verhage and Smit.
Max Planck Institute of Experimental Medicine
Main task in COSYN: The joint groups of Rhee and Brose were responsible for the analysis of synapse function in single iPS cell derived neurons from selected patients. For this purpose, they designed and optimized single neuron microisland (autaptic) cultures for the standardized analysis of single neurons from many different genotypes (i.e., different patients). This approach allowed to study – in a standardized fashion – many morphological and functional features of neurons. They closely collaborated with Verhage, with whom they shared the task to perform these standardized autaptic analyses.
PI: Oliver Brüstle, email@example.com
Department: Director of Reconstructive Neurobiology, www.meb.uni-bonn.de/rnb/index.php?page=institute-of-reconstructive-neurobiology
Main task in COSYN: Universitätsklinikum Bonn derived patient-specific induced pluripotent stem cells (iPSCs) for subsequent neuronal differentiation and functional characterization. To this end the group of Brüstle obtained patient blood cells from the consortium and generate iPSC lines using non-DNA-integrating reprogramming technologies. Partner Life & Brain will by using the StemCellFactory (http://www.stemcellfactory.de/index.php?page=home-en) facilitated iPSC production in both standardization and scale. CRISPR-Cas9-based genome editing was used to repair risk alleles and generate isogenic controls since it is possible that even strong risk alleles might elicit only subtle cellular or synaptic changes, which can be difficult to distinguish from intrinsic variability. Neurons derived from the iPSCs and editing were then be shipped to COSYN partners that performed cellular assays, in particular the Brose, Verhage and Smit labs.
PI: Michael O’Donovan, firstname.lastname@example.org
Department: MRC Centre for Neuropsychiatric Genetics and Genomics, www.medicine.cf.ac.uk/person/prof-michael-conlon-odonovan/
Main task in COSYN: Owen was leader of WP 2 which was responsible for identifying, evaluating and obtaining biological samples from patents with specific mutations relevant to ID, autism and schizophrenia. The research group in Cardiff has contributed cases with a diagnosis of schizophrenia. This work was instrumental for the selection of stem cell differentiation and downstream functional analysis in WP3.
Helsingin Yliopisto /University of Helsinki
PI: Professor Aarno Palotie, email@example.com
Department: Institute for Molecular Medicine Finland (FIMM) (Genomics of Neurological and Neuropsychiatric disorders), www.fimm.fi/en/research/groups/palotie
Main task in COSYN: Palotie’s group in Helsinki mainly contributed to WP2 with cases in intellectual disability (ID), and to WP 6 for case studies on precision medicine for ID. Overall, Palotie’s group also provided genetic expertise in neuropsychiatric disorders through established international networks. Like Owen, Palotti’s contribution was essential in selecting cases for which stem cell differentiation and cellular phenotyping performed in WP3.
PI: Professor and Project Vice-Coordinator Matthijs Verhage, firstname.lastname@example.org
Department: Faculty of Earth and Life Sciences (Functional Genomics)/ VU Medical Center, Clinical Genetics, www.cncr.nl
Main task in COSYN: The Verhage team was responsible for the analysis of synapse function in single iPS cell derived neurons from selected patients. To this end his lab optimized single neuron micro-dot cultures for the standardized analysis of single neurons from many different genotypes (i.e., different patients). They also optimized high content assays using electrophysiology and live cell imaging to produce extensive parameter sets on synapse function from these neurons/patients. His team was also involved in the generation of analysis algorithms for the (statistical) analysis of such complex data and for their presentation and interpretation.
PI: Professor Dr. Guus Smit, Guus.email@example.com
Department: Faculty of Earth and Life Science (Molecular and cellular neurobiology), cncr.nl/about_cncr/word_from_the_director
Main task in COSYN: The Smit laboratory was responsible for the high content screening (HCS) of human neurons derived from patient iPS cells. HCS allows this team to gather high-resolution microscopy data of neurons grown in vitro. In particular, this type of analysis should provided data on the relationship of genetic make-up of cells and their cellular phenotypes and subsequently aided the generation of assays that could be used for drug screening. HCS data was part of the larger collection of cellular data that were acquired by the Brose, Verhage and the Smit teams.
Main task in COSYN: The Posthuma team was co-responsible for selecting genetically informative patients for iPSC and functional follow-up and will provide the main statistical genetic analyses and bioinformatics tools and analyses pipelines to (i) determine the most plausible genetic drivers of comorbidity between ID, autism and schizophrenia (ii) prioritize gene targets and pathways for functional follow up in other WPs (iii) conduct multilevel statistical analysis on produced data on the level of the cellome, proteome and transcriptome. This type of analysis was instrumental to arrive at a higher level of integration of genetic and experimental data within COSYN.
PI: Thomas Werge, firstname.lastname@example.org
Department: Mental Health Centre Sct. Hans, http://ipsych.au.dk/about-ipsych/research-groups/thomas-werge-group/
Main task in COSYN: Werge’s Lab main task was to recruit carries with the 22q11 deletion syndrome and provide samples for IPSC generation. They have been working extensively with this particular group of deletion carriers, and a subset of the subjects has been deeply phenotyped (psychopathology, EEG, MRI, metabolomics, RNA-seq, and 3D facial imaging) and genomic characterized (have GWA genotyping, CNVs and WES).
PI: Maarten Loos PhD, email@example.com
Department: CEO, www.sylics.com
Main tasks in COSYN: The team at Sylics assessed the effects of selected compounds in preclinical mouse models of human diseases. The effect of these compounds were measured using automated home-cage based testing protocols developed by Sylics, avoiding stressful human-mouse interactions that are normally required for preclinical testing. In addition, the team at Sylics contributed to administrative management and as WP7 leader.
PI: Saskia Biskup MD PhD, firstname.lastname@example.org
Department: Managing Director, http://www.cegat.de/en/company/
Main task in COSYN: CeGaT GmbH is a global provider of genetic diagnostics and mutation-related disease analyses. CeGaT has specialized in the use of next-generation sequencing since its foundation and already uses this technology as a service for customer-oriented research projects. Within COSYN CeGaT was responsible for the performance of genetic sequencing analyses. This included the identification of genomic rearrangements and off target effects of genome editing. CeGaT also performed quality control testing to ensure the genomic stability and cell identity of cultured patient-derived cells. As such CeGaT generated data that essentially supported decision-making between the first genetic selection and the follow-up at the cellular phenotyping level.
LIFE & BRAIN GmbH
PI: Simone Haupt, email@example.com
Department: Cellomics Platform, http://lifeandbrain.com/
Main task in COSYN: LIFE&BRAIN employed protocols for the in vitro differentiation and cryopreservation of iPSC-derived mature neurons with properties specific for different layers of the neocortex. Standardized cell preparations from large iPSC collections were provided to partners involved in functional analyses and other phenotypic read-outs. For iPSC generation from patient sample collections LIFE&BRAIN contributed bioreactor technologies and automated cell culture systems tailored for the automated reprogramming and expansion of human iPSCs (www.stemcellfactory.de). In close collaboration with Universitätsklinikum Bonn LIFE&BRAIN safeguarded the production of high-quality iPSC lines and iPSC-derived cortical neurons for comparative studies performed by COSYN partners. This activity was at the basis of all the cellular phenotyping performed in WP3, and 4, by the Brose, Verhage and Smit teams.
H. Lundbeck A/S
PI: Michael Didriksen PhD, firstname.lastname@example.org
Department: Disease Biology Research, www.lundbeck.com/global/about-us
Main task in COSYN: Lundbeck A/S is a drug development company of approximately 5000 employees. Lundbeck A/S has facilities to conduct research covering the entire value chain from basic molecular in vitro studies, over advanced behavioral in vivo studies to full clinical development and marketing of CNS acting drugs. They were involved in optimizing assays developed in COSYN for large scale screening and utilize their capabilities to conduct screening of compound libraries to identify novel drug targets. As such, the Lundbeck activities assisted in bridging the COSYN academic efforts with the applications in drug discovery.
F. Hoffmann-LA Roche
PI: Dheeraj Malhotra, email@example.com
Department: Synapse and Circuits, http://www.roche.ch/en/standorte/basel-hq.htm
Main task in COSYN: Roche’s Neuroscience department combines world-leading science in neurodevelopmental, neuropsychiatric and neurodegenerative disease areas where they have a long and successful track record with new avenues of research that hold tremendous promise for millions of patients and their caregivers worldwide. Roche was involved in supporting the generation and functional characterization of patient specific iPSC cell lines and neurons in WP3 and 4. Roche also supported optimizing cellular assays developed in COSYN. This step was essential as a fundament of future large-scale compound screening campaigns.
3. Patient Organisation
Main task in COSYN: VSOP has set up the Patient Advisory Board (PAB), consisting of expert-patients who interact with, and advice, the scientific project partners on any scientific, ethical, communicational and implemental issue that may affect the lives of people living with an intellectual disability, autism or schizophrenia. PAB-members were consulted regularly before and during project meetings, and were available on an ad hoc basis when issues arose that require the patient’s perspective.
4. Ethical advisor
Eline Bunnik – External Ethics Advisor, firstname.lastname@example.org
Main task in COSYN: As an external Ethics Advisor she identified and addressed ethical issues that arose throughout the research project. She promoted compliance of the consortium with international and national research ethics guidelines, provided independent advice to the consortium, and reported to the EC policy officer of the project.