Research
Every neuron needs to decide which of its tens of thousands of genes to express and how much of each gene product to make. As an animal navigates the world, these neuronal gene expression decisions are continually updated based on the environment. We aim to understand how an animal’s experience alters the gene expression profiles of its neurons, and how these gene expression responses generate plasticity. To address this question, we use an ideal model system – sensory neurons of the nematode C. elegans. This system has a number of advantages: 1) These neurons can be activated by quantitatively controlled, ecologically relevant environmental stimuli; 2) C. elegans sensory circuits drive well characterized behaviors and behavioral plasticity; 3) Individual C. elegans neurons are identifiable and invariant from one animal to the next, meaning we can do experiments at true single neuron resolution; 4) We can predict, manipulate, and causally test the functions of individual gene regulatory elements, such as transcription factor binding sites,
in a fully intact and behaving worm.
We use single-neuron sequencing approaches to measure experience-dependent gene expression profiles, CRISPR-Cas9 to generate endogenous expression reporters and manipulate regulatory circuits, and calcium imaging and behavior assays to ultimately causally link experience-dependent regulation of gene expression to neuronal plasticity.