PiN Faculty Member - Jesse Gray, PhD

Jesse Gray, PhD

Assistant Professor in Genetics

Harvard Medical School
New Research Building, Room 0356
77 Avenue Louis Pasteur
Boston, MA 02115
Tel: 617-432-1877
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 neuronal circuits. We are applying genetics and genomics to understand how signaling pathways and genomic regulatory sequences translate patterns of neuronal activity into gene expression states and cellular outcomes.

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 what does the expression of Fos or other genes convey about the activity history of a neuron? We recently took a step toward defining the neuronal-activity-to-gene-expression coupling map in mouse cortical neurons using multiplexed RNA-Seq. The coupling map is a practical tool in analyzing single cell RNA-seq data, since it enables inference of activity history from gene expression alone.

Our finding that different activity-regulated genes interpret patterned neuronal activity differently raises the question of how the neuronal-activity-to-gene-expression coupling map is 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.

Neuronal activity-regulated transcription can prevent runaway excitation, and we hypothesize that it is a key component of a control circuit for neuronal excitability, one that controls neuronal activity much like a thermostat maintains temperature. We are investigating this idea by directly tracking the ability of neurons to homeostatically adapt to firing rate perturbations. Another major function of neuronal activity-regulated transcription may be to promote dynamic axonal myelination during learning. We are investigating this idea by assessing experience-dependent myelination during motor learning.



Last Update: 12/5/2018



Publications

For a complete listing of publications click here.

 


 



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