# Microbial Modulation of Neuroendocrine Physiology and Aging of C. elegans

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2020 · $447,900

## Abstract

Host-microbiota interactions have been implicated in diverse effects ranging from immune system
development to metabolism and behavior. Recent studies implicate a pivotal role for microbial metabolites that
may act on the host. In the most recent funding period of our grant, we have shown that in the simple animal
host Caenorhabditis elegans, chemosensory recognition of specific virulence-associated secondary metabolites
produced by Pseudomonas aeruginosa activates a G protein-dependent signaling pathway that alters the
neuronal expression pattern of DAF-7, a neuronal TGFβ ligand with restricted expression that has previously
been shown to regulate diverse aspects of C. elegans physiology. Induction of DAF-7 expression in the ASJ
sensory neuron pair acts on specific promoters to promote behavioral avoidance by C. elegans. This behavioral
phenotype and quantitative analysis of DAF-7 expression changes is further complemented by calcium imaging
with GCaMP of ASJ neuron activation in response to bacterial metabolites. Our data have established an
experimental system in a simple, genetically tractable host with a well-defined nervous system, which we can
use to define the molecular mechanisms by which microbial metabolites can influence host physiology and
behavior. From the analysis of over twenty mutants that exhibit defective daf-7 transcriptional responses in the
ASJ neurons in response to P. aeruginosa, we have identified distinct candidate calcium-dependent signaling
pathways that regulate the host neuroendocrine response to P. aeruginosa metabolites. We have also carried
out preliminary RNA-seq of ASJ neurons that have been separated and FACS-sorted, which reveal a number of
candidate genes involved in the regulation of C. elegans neuronal responses to P. aeruginosa. We will conduct
molecular genetic analysis to establish the signaling pathways that transduce the detection of microbial
metabolites to altered DAF-7 transcription, and we will define the mechanisms by which DAF-7 expression in
the ASJ neurons in regulated. We will also test the hypothesis that microbial metabolites also modulate
neuroendocrine insulin signaling, and carry out a systematic functional analysis of the transcriptional
responses of the ASJ neuron pair to microbial metabolites. We anticipate that defining the molecular
mechanisms underlying how specific microbial metabolites can modulate the activities of conserved
neuroendocrine signaling in C. elegans will yield insights into evolutionarily conserved interactions between
microbiota and their animal hosts.

## Key facts

- **NIH application ID:** 9964840
- **Project number:** 5R01GM084477-13
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Dennis H Kim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $447,900
- **Award type:** 5
- **Project period:** 2007-09-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9964840

## Citation

> US National Institutes of Health, RePORTER application 9964840, Microbial Modulation of Neuroendocrine Physiology and Aging of C. elegans (5R01GM084477-13). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9964840. Licensed CC0.

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