Proposal presented herein combines methods of synthetic organic chemistry, cellular neurobiology, and chemical biology to study processes involved in neuronal differentiation and regeneration that would catalyze establishment of research environment at Masaryk University centered around the applicant’s laboratory where small-molecule tools are used to perturb biological events. Small-molecule approach is perhaps best considered complementary to the alternative methods of dissecting of biological processes. The latter include gene knock-in/knock-out, protein-specific antibodies, engineered recombinant proteins, and RNA interference. Primary advantage of such established tools, as compared to small molecules, is the existence of robust and rapid protocols for their production and selection, providing reagents with typically high selectivity for the target of interest. Limitations of these methods become however apparent when it comes to the study of dynamic and time-dependent events and also in cases where the key proteins driving biological effect are difficult to interfere with or are not known. Applicant is broadly interested in uncovering the exciting potential of small molecules in study of dynamic processes of neuronal differentiation and regeneration, even though the characterization and development of small-molecule probes is presently more challenging.

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