PiN Faculty Member - Jesse Gray, PhD

Jesse Gray, PhD

Assistant Professor in Genetics

Harvard Medical School
Department of Genetics
New Research Building, Room 0356
77 Avenue Louis Pasteur
Boston, MA 02115
Tel: 617-432-7667
Fax: 617-432-7595
Email: gray@genetics.med.harvard.edu
Visit my lab page here.



The genome responds to experience by unleashing bursts of new gene expression that rewire circuits to store long-term memories. These bursts rely on a network of neuronal activity-regulated transcription factors that bind genomic regulatory sequences. How these regulatory sequences translate specific patterns of neural activity into corresponding gene expression states remains unknown. We are applying genomics and systems biology approaches to address this question. At the same time, we are investigating the contribution of activity-regulated transcription to plasticity and associative memory formation in the mouse neocortex.

We are addressing the following more specific questions:

What does it mean when Fos is expressed in a neuron? Fos and other neuronal activity-regulated genes are transcribed in response to increases in neuronal activity and have long been used as activity reporters. Yet  the so-called "transfer function" between neural activity and gene expression has not been defined. In other words, what the expression of Fos conveys about the activity history of a neuron is not known. We are defining the transfer function in mouse cortical neurons, where we can control neuronal firing rates optogenetically and measure gene expression using multiplexed RNA-Seq.

How are transcriptomic computations encoded in signaling pathways and regulatory sequences? We have found that different activity-regulated genes interpret patterned neuronal activity differently, raising the question of how particular response properties or transfer functions are encoded in genomic regulatory sequences. To address this question, we manipulate activity-regulated transcription factors genetically and assess transcriptional responses using chromatin immunoprecipitation sequencing and RNA sequencing. We also interrogate activity-regulated genomic DNA elements functionally, using a high-throughput screening approach built on viral libraries of barcoded reporter genes.

How does activity-regulated transcription contribute to long-term memory formation in the neocortex? Neuronal activity-regulated transcription has long been implicated pharmacologically and genetically in long-term memory formation. Yet its specific contribution is unknown, in part because the the physical substrate of associative memory in the brain -- the so-called memory trace -- has yet to be defined. We manipulate activity-regulated transcription to investigate which of the cell biological forms of plasticity that occur during learning are transcription-dependent, with the ultimate goal of understanding how activity-regulated transcription stabilizes a memory trace.



Last Update: 8/18/2016



Publications

For a complete listing of publications click here.

 


 



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