The main task of Sylics (the tradename of Synaptologics BV) within SYNSYS is to provide a smooth operation process by supporting coordination and management activities of the coordinator. Whereas the coordinator (Smit) will be responsible for the overall program, and in particular for the financial mangement, Sylics will focus on project management and logisitcs, specifically implementing optimized and customized solutions for the partner groups, e.g., providing updated timetables and budgets, providing meeting schedules and organizing conferences, drafting reports and provide reporting to the EU, engaging in data-dissemination and webhosting as well as organizing webinars enhancing networking and training activities.

Beactica will develop assays for studying the interactions between synaptic proteins and perform detailed interaction studies of selected proteins. By competition experiments and ligand interference studies followed by computational structure modelling, the interactions will be structurally mapped. The kinetic details and importance of experimental conditions for the interactions will be explored in order to determine the characteristics of the interactions and their regulation. Models for protein interaction networks will be developed.

BWD will provide contract services whereby proteins identified by the SynSys partners as potential disease candidates will be engineered in normal and/or variant form into the fly brain. They will then be profiled using an array of physiological, anatomical and behavioural tests. These technologies will provide a system whereby new candidates can be assessed very rapidly and cost-effectively (approx 5x faster and 5x cheaper than rodent models) yet sill providing real living brain information. This will reduce the overall animal use by the consortium.

The main task will be to exploit Synome’s MEA methods to study the effects of gene disruption (WP 5) on synaptic physiology and network oscillations in brain slices on MEA. These in vitro neural network assays are complementary to physiological methods either in slices or patch clamping used in other WPs.

The main areas of activity will lie in: gathering human genetic variation, quality control and co-analysis of GWAS data, contribution of cohorts Finrisk, Health 2,000 and NFBC1966 for the common consortium database (in WP2) (total n= 73,204, GWA 8,129)

The group will focus on providing the mRNP composition of the synaptosomes during development. The mRNA/RNA content will be analyzed on microarrays (in the dedicated VIB facility). In a parallel study we will isolate native mRNPs (translating and silent) through well-established sucrose gradients and the content of the two different components (RNA and protein) analyzed independently (microarray and mass spec). Finally these studies will be performed for a pathological condition such as mental retardation using three mouse models to study the Fragile X Syndrome and Autistic Spectrum Disorder.

The group will contribute to the consortium its expertise in study of intracellular signaling networks in vivo and in vitro. The work will include in vivo and in vitro studies of G proteins, protein phosphorylation pathways and other post-translational modifications in response to pharmacological and behavioural stimulation in wild type and mutant mice. They will study signaling at the synaptic and at the nuclear levels including its output on gene expression. They will closely interact with other partners and provide data for models and test hypothesis derived from these models.

The main task of this project partner is (A) the functional analysis of genes expressed in the presynaptic nerve terminal (B) generation of dynamic models for the presynaptic gene network and (C) the collective testing of genes in such networks for association of variation with human brain traits such as cognition and several brain disorders. The department has an extensive track record in the functional analysis of synaptic transmission, human genetics of cognition and secretory vesicle trafficking using a wide variety of high-end methods.

The main task of the group will be the investigation and analysis of the proteins of the synaptic proteome and the prediction of protein-protein interactions derived from conserved protein domain contacts. Putative binding sites will be further validated experimentally by the design of non-linear peptide libraries representing the interacting sites followed by the synthesis and screening of peptide microarrays. Furthermore, the experience in the design of peptidomimetics will be applied to interfere with specific protein-protein interaction or to disturb the complex formation of proteins.

The main task of the group will be the investigation and analysis of the proteins of the synaptic proteome and the prediction of protein-protein interactions derived from conserved protein domain contacts. Putative binding sites will be further validated experimentally by the design of non-linear peptide libraries representing the interacting sites followed by the synthesis and screening of peptide microarrays. Furthermore, the experience in the design of peptidomimetics will be applied to interfere with specific protein-protein interaction or to disturb the complex formation of proteins.