University of Cambridge > > Babraham Seminar > 3D genome folding, unfolding, and refolding in the mammalian brain

3D genome folding, unfolding, and refolding in the mammalian brain

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  • UserDr Jennifer E. Phillips-Cremins; University of Pennsylvania, Philadelphia USA
  • ClockWednesday 22 September 2021, 15:00-16:00
  • HouseZoom webinar.

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This webinar will be online via zoom. No registration required.

The Cremins Lab focuses on higher-order genome folding and how classic epigenetic modifications work through long-range, spatial mechanisms to govern synaptic plasticity in healthy and diseased neural circuits. Much is already known regarding how transcription factors work in the context of the linear genome to regulate brain development. Yet, severe limitations exist in our ability to engineer chromatin in neural circuits to correct synaptic defects in vivo. At the lab’s inception, it remained unclear whether and how genome folding could functionally influence cell type-specific gene expression. We have developed and applied new molecular and computational technologies to discover that nested subTADs and long-range loops undergo marked reconfiguration during neural lineage commitment, somatic cell reprogramming, neuronal activity stimulation, and in repeat expansion disorders. We demonstrated that loops induced by neural circuit activation, engineered through synthetic architectural proteins, and miswired in fragile X syndrome were tightly connected to transcription, thus providing early insight into the genome’s structure-function relationship. We are currently focused on understanding how, when, and why 3D genome folding patterns contribute to synaptic plasticity and dysfunction in neural circuits. Addressing this knowledge gap will provide an essential foundation for our long-term goal to engineer the 3D genome to reverse pathologic synaptic defects in debilitating neurological diseases.

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