# Genetic analyses of complete circuit formation in Caenorhabditis elegans

> **NIH NIH F32** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 2021 · $34,281

## Abstract

Project Summary / Abstract
Despite the central importance of neural circuit development to brain function and behavior, we lack the genetic
information required to assemble a complete circuit. To address this knowledge gap we propose to develop
novel synaptic and neuronal-neighborhood techniques to label a complete circuit in live animals. Using these
tools we will genetically dissect a complete neural circuit for the first time, providing fundamental genetic insight
into how circuits are built. We will take advantage of C. elegans biology - its available ultrastructural
connectome and facile genetics, to address questions of synaptic wiring throughout a complete circuit. We will
leverage the extensive genetic and anatomical knowledge of the C. elegans pharynx, a small but functionally
independent circuit, as a model. We will for the first time create an expression map of all neurons in a circuit
using neuron-specific FACS and transcriptomic profiling. We will then correlate these new gene expression
maps to the ultrastructural connectome to reveal how patterns of gene expression correlate with connectivity.
Next, we will construct fluorescent reporter systems to (1) label the entire pharyngeal circuit using GFP
Reconstitution Across Synaptic Partners (GRASP) and (2) label the neighborhoods of adjacent neuronal
processes using CD4-based in vivo Biotin Labeling of INtercellular Contacts (iBLINC). Using these tools, we
will perform a genome-wide RNAi screen of cell surface proteins to determine their role in all major steps of
circuit formation – neuronal outgrowth, neighborhood, and synaptic choice. The results from this proposal will
identify and validate genetic factors controlling wiring that can be further evaluated in complex vertebrate
nervous systems and humans. This proposal will not only improve methodologies for fluorescent labeling of
synapses and neuronal neighborhoods, but will provide an exquisitely detailed map-based understanding of a
circuit in live animals. Furthermore, our approach and results will be useful in the broad context of
understanding fundamentals of circuit formation applicable across brain complexity.

## Key facts

- **NIH application ID:** 10347165
- **Project number:** 5F32MH115438-04
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **Principal Investigator:** STEVEN JAY COOK
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $34,281
- **Award type:** 5
- **Project period:** 2017-09-27 → 2021-03-26

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10347165

## Citation

> US National Institutes of Health, RePORTER application 10347165, Genetic analyses of complete circuit formation in Caenorhabditis elegans (5F32MH115438-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10347165. Licensed CC0.

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