The science of connections: Bridging chromatin, synaptic plasticity, and neurophysiology

In this talk, Jennifer E. Phillips-Cremins provides insight into the work at the Cremins Laboratory, working at the spatial biology-technology interface to investigate the structure-function relationship of connections across the scales of chromatin, synapses, and circuits in the developing and diseased mammalian brain. They have thus far focused in the nucleus to understand how classic epigenetic modifications work through long-range physical folding mechanisms to govern genome function. At the lab’s inception, it was unknown how genomes fold in the mammalian brain below the resolution of a Megabase (Mb), and whether and how higher-order chromatin structure could deterministically influence genome function. 

The lab has developed and applied new molecular and computational technologies to elucidate chromatin folding patterns at kilobase-resolution genome-wide, thus discovering that long-range loops in cis and inter-chromosomal interactions in trans change substantially and functionally contribute to new gene expression patterns during neural lineage commitment, somatic cell reprogramming, neural maturation during brain development in vivo, stimulation of neural circuits in vitro, and in neurological disorders of fragile X syndrome (FXS) and familial Alzheimer’s disease (FAD). The long-term goal is to elucidate how the genome’s structure-function relationship influences synaptic plasticity during memory encoding and consolidation and how this goes awry in intractable neurological disorders. 

Phillips-Cremins will be hosted by Kristen Brennand (Psychiatry, Genetics).