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Small-Molecule Probes of Neuronal Differentiation (SMOLDIF)
Date du début: 1 nov. 2012, Date de fin: 31 oct. 2016 PROJET  TERMINÉ 

"Proposal presented herein combines methods of synthetic organic chemistry, cellular neurobiology, and chemical biology to study processes involved in neuronal differentiation. The primary objective of the project is to discover, characterize, and make broadly available high-quality research tools useful in studies of the dynamic processes of differentiation. The outcome of the project is expected to be of immediate value to the basic research in neurobiology, with potential for clinical applications.To perturb the dynamic process of neuronal differentiation, a small-molecule approach will be pursued. Chemical synthesis will play a central role in providing access to structurally complex molecules that are nontrivial to prepare and, partly as a consequence, underrepresented in the commercial vendor libraries. Ability of the prepared molecules to affect neuronal differentiation will be assessed in phenotype-based assay employing physiologically relevant neuronal cultures. Identification of cellular targets binding to the active small molecules will be an integral part of the project and will make use of small molecule-derived reagents and proteomic analysis. A link between the small-molecule structure, neuronal phenotype, and cellular proteins affected by the small molecule, will be instrumental en route to the small-molecule probes of neuronal differentiation.The multidisciplinary nature of the project necessitates interaction among several laboratories, including the applicant’s laboratory for organic synthesis, in order to realize the objectives of the proposal. Establishment of such research environment will catalyze applicant’s integration into the scientific community of Masaryk University in the Czech Republic and development of lasting scientific connections within the region (“centers of excellence” FNUSA-ICRC and CEITEC) and Europe-wide (Max Planck Institute of Molecular Physiology)."