# Rid family members neutralize endogenous metabolic stressors

> **NIH NIH R01** · UNIVERSITY OF GEORGIA · 2022 · $330,652

## Abstract

SUMMARY
 A fundamental feature of a living system is its integrated network of biochemical pathways that respond to
endogenous and environmental stresses. In humans, there is a strong connection between metabolic network
dysfunction and disease. Metabolic strategies are conserved across biology, and insights obtained from model
organisms provide the means to advance our understanding of general metabolic paradigms, which can often
be extrapolated to higher organisms including humans. The long-term goal of the PI's research is to
understand the robustness and redundancy of the metabolic network, and to define metabolic components and
the processes they participate in. Knowledge of metabolic processes and a mechanistic understanding of the
function of unknown proteins is critical to efforts aimed at treating metabolic diseases, and to efforts targeting
metabolism for rational drug design, synthetic biology, microbiome research, etc.
 The goal of the work proposed herein is to advance our understanding of the metabolic stress caused by the
2-aminoacrylate, an obligate intermediate in central metabolic reactions, and the protein that controls it, RidA.
Further, this study focuses on the highly conserved Rid protein family, of which RidA is the founding member.
In the current proposal we will: i) describe additional, distinct mechanisms that have evolved to deal with
similar stress; ii) explore the breadth of 2-aminoacrylate stress and how different organisms handle it, and iii)
define the molecular mechanism and cellular role of additional Rid proteins. The goals of this proposal will be
accomplished through a combination of chemical, biochemical, molecular genetic, bioinformatics and global
approaches. The work here is motivated by our desire to understand the metabolic stress generated by the
production of reactive metabolites during growth, how it can damage cellular components if it is not neutralized,
and discovering the role of additional members of the broadly conserved protein family that includes RidA.

## Key facts

- **NIH application ID:** 10469647
- **Project number:** 5R01GM095837-12
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Diana M. Downs
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $330,652
- **Award type:** 5
- **Project period:** 2011-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10469647

## Citation

> US National Institutes of Health, RePORTER application 10469647, Rid family members neutralize endogenous metabolic stressors (5R01GM095837-12). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10469647. Licensed CC0.

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