# Biochemical and functional investigation of the novel enzymatic activities of MESH1

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $70,500

## Abstract

Abstract
The main strategy for bacteria to cope with metabolic stresses is through the stringent response
triggered by the accumulation of the alarmone (p)ppGpp. While metazoan genomes also
encode a homologue of the (p)ppGpp hydrolase SpoT (MESH1), neither a homologue of the
(p)ppGpp synthetase nor (p)ppGpp itself has been found in metazoa. Therefore, the stringent
response was thought to be absent in metazoa. Unexpectedly, we found that the silencing of
MESH1 in mammalian cells triggered a cellular response highly similar to the bacterial stringent
response characterized by the short-term stress survival, reversible proliferation arrest as well
as extensive transcriptional and metabolic reprogramming. Therefore, we investigate the in vivo
function of MESH1 during disease-relevant stresses in liver and kidney. Therefore, the MESH1
plays an intriguing function in the mammalian stress adaptations. However, the bulk cell
analysis of the liver and kidney limited our understanding of the relevant affected cell types and
association with the enzymatic activities of MESH1. Therefore, we are seeking support to obtain
a 10X Genomics Chromium controller that will enable single cell RNA-Seq to elucidate the
underlying mechanisms of MESH1 during the injury of kidney and liver. The availability of such
instrument will allow us to conduct reliable and reproducible RNA-Seq experiments to elucidate
the biochemical basis and functional relevance of the MESH1 in the mammalian stresses
response.

## Key facts

- **NIH application ID:** 10131669
- **Project number:** 3R01GM124062-03S1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Jen-Tsan Ashley Chi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $70,500
- **Award type:** 3
- **Project period:** 2018-07-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10131669

## Citation

> US National Institutes of Health, RePORTER application 10131669, Biochemical and functional investigation of the novel enzymatic activities of MESH1 (3R01GM124062-03S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10131669. Licensed CC0.

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