# Identifying molecular mechanisms of responding to gravity using the nematode C. elegans

> **NIH NIH R21** · UNIVERSITY OF PENNSYLVANIA · 2024 · $235,938

## Abstract

ABSTRACT
Impaired ability to respond to the earth’s gravitational field and loss of balance results in high risk of falls with
adverse consequences for one’s health, quality of life, and health care costs to society. Falls are a particular
risk for individuals with Parkinson’s disease as well as elderly humans in general. Despite the importance of
gravity sensing to daily activities, the molecular, cellular, and circuit gravity sensing mechanisms are
incompletely understood. To understand gravity sensing mechanisms at the molecular and neural circuit level,
we use the simple microscopic nematode Caenorhabditis elegans. C. elegans offers many experimental
advantages, including a small and simple nervous system, accessibility to rapid genetic manipulation and to
optogenetic tools, and ease of cultivation. We have demonstrated that C. elegans senses and responds to
gravity, and have used mutant analysis and pharmacology to show that one or more types of ciliated sensory
neurons, as well as dopamine, play a role in gravitytaxis. Our preliminary data leads to the hypothesis, which
we will test, that one or more of the three ciliated dopaminergic neurons types—CEP, ADE, and/or PDE—
mediates the response to gravity. We will use genetically-encoded synaptic transmission toxins as well as
genetically-encoded chemogenetic experiments to determine which of these 3 neuron types is required for the
response to gravity. We will identify additional neurotransmitters required for gravitaxis by testing animals
mutant for each of 4 neurotransmitter systems. We will test each of 58 C. elegans genes predicted to encode
mechanosensitive ion channels for a role in gravitaxis. Finally, we will make use of the million mutation project
to perform a pilot unbiased genetic screen for gravitaxis-defective mutants. In addition, we will develop a high
throughput sorter to isolate gravitaxis – deficient mutants for a future high throughput genetic screens for
additional gravitaxis defective mutants. At the completion of these studies, we will have identified one or more
dopaminergic neuron type as well as other neurotransmitters required for gravitaxis and we will have
developed the tools needed for further studies consistent with the objectives of this R21
exploratory/development funding mechanism. Our work will contribute to a comprehensive molecular
understanding of animals’ response to gravity and set the stage for the development of novel therapeutics to
reduce falls.

## Key facts

- **NIH application ID:** 10988638
- **Project number:** 1R21AG085030-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Haim H Bau
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $235,938
- **Award type:** 1
- **Project period:** 2024-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10988638

## Citation

> US National Institutes of Health, RePORTER application 10988638, Identifying molecular mechanisms of responding to gravity using the nematode C. elegans (1R21AG085030-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10988638. Licensed CC0.

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