# Molecular dissection of glia-neuron interactions

> **NIH NIH R01** · FRED HUTCHINSON CANCER CENTER · 2022 · $425,812

## Abstract

PROJECT SUMMARY
Our long-term aim is to understand glial roles in nervous system health, aging and disease in molecular detail.
The human nervous system has about equal numbers of glia cells and neurons, and interactions between
these two cell types is critical for neural functions. An important site of contact between glia and neurons is the
neuron-ending, where neurons receive input from other neurons (interneuron dendritic spine) or the
environment (sensory receptive-endings). Neuron-ending shape dictates appropriate neuron connectivity and
functions, including sensory perception and learning and memory. While it is appreciated that glia modulate
neuron-ending shapes and functions, molecular mechanisms underlying this remain poorly defined. Indeed,
many fundamental principles of glia-neuron interactions remain unclear, such as whether all glia-neuron pairs
interact using identical molecular mechanisms. It is however important to address this gap in our
understanding of glial functions, because impaired glia-neuron interactions are implicated in many neurological
diseases such as Alzheimer’s disease, Autism, epilepsy and may contribute to neural decline with age.
We propose to dissect glia-neuron interactions in molecular detail in vivo, using C. elegans as a powerful and
genetically amenable experimental platform. C. elegans glia resemble vertebrate glia, and our recent studies
have validated this as a powerful setting to rapidly probe glia-neuron molecular interactions. We previously
identified two novel molecular mechanisms by which glia interact with neurons to regulate their shape,
functions and associated animal behaviors. All molecular components of these mechanisms that we have
uncovered so far are broadly expressed, suggesting that aspects of glia-neuron interactions are evolutionarily
conserved across species. Importantly, C. elegans glia are accessible for rapid and reproducible genetic and
cellular manipulations in vivo. Effects of such manipulation can be investigated at multiple levels of inquiry,
from molecular (genetic, genomic, protein biochemistry), cell-biology (cell shape, cell-cell contacts) and circuits
(functional imaging, mapped connectome) to animal behavior and aging studies, and disease models
(Alzheimer’s, Parkinson’s). Here, we propose to dissect molecular mechanisms of glia-neuron interactions
throughout animal age in detail. For this, we will couple the experimental platform we established, and
techniques described above, with the multiple genetic mutants we recently identified to (1) determine how
multiple molecular pathways together enable interactions between a single glia-neuron pair; (2) investigate in
mechanistic detail how a single glia can differentiate associated neurons to regulate them differently, and (3)
dissect mechanisms by which different glia-neuron pairs interact to regulate neuron functions with age.
Together, these studies will build a comprehensive molecular framework of how a glia cell modula...

## Key facts

- **NIH application ID:** 10465115
- **Project number:** 5R01NS114222-04
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Aakanksha Singhvi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $425,812
- **Award type:** 5
- **Project period:** 2020-09-30 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465115

## Citation

> US National Institutes of Health, RePORTER application 10465115, Molecular dissection of glia-neuron interactions (5R01NS114222-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10465115. Licensed CC0.

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