Timothy Bredy, Ph.D.
My work in cognitive neuroepigenetics has been driven by a strong interest in understanding and elucidating the molecular mechanisms of how environmental stimuli and experience translate into long-term memories. Epigenetics, broadly defined, refers to all genetic information not encoded in the DNA sequence, with the best-understood consequence of epigenetic modifications being the regulation of gene expression. Although gene transcription and protein synthesis is required for the formation of memory, the full repertoire of epigenetic mechanisms underpinning this crucial biological adaptation remain equivocal. Post-translational modification of histone proteins (i.e. acetylation, methylation etc.) and the covalent modification of DNA (i.e. methylation, hydroxymethylation and other recently discovered marks) can influence the function of the genome in a myriad of ways including the regulation of alternative splicing and transposable elements, the development of bivalent chromatin marks that render genes “poised” for transcriptional activity, and by directing nucleosome repositioning to “bookmark” recently activated genes. In addition, the majority of the genome is pervasively transcribed such that upwards of 90% of transcriptional activity is related to the production of various long non-coding RNAs (lncRNA), which possess no protein-coding capacity. The expansion of these transcriptionally active non-coding sequences in the mammalian genome appears to have occurred primarily in species with higher-order cognitive function and brain-enriched lncRNAs are expressed in both a spatiotemporal- and cell-type-specific manner. Furthermore, emerging evidence indicates that these enigmatic non-coding RNAs can function as decoys for transcription-related factors, as modular scaffolds, or as guides to direct chromatin-modifying complexes to their genomic sites of action. Thus, lncRNAs represent attractive candidates for achieving context- and stimulus-specific epigenetic regulation of gene expression; however, their role in cognition and memory remains unexplored.
Key Research Areas:
Memory, fear, extinction, PTSD, phobia, epigenetics, non-coding RNA, RNA modification, epitranscriptomics, DNA structure, activity-dependent gene expression