# Starvation resistance and resilience of metabolic dysfunction in cavefish

> **NIH NIH DP2** · STOWERS INSTITUTE FOR MEDICAL RESEARCH · 2020 · $2,475,000

## Abstract

Project Summary
The overarching goal is to understand the complex genetic network regulating energy metabolism. This is a
critically important problem from the standpoint of human health, and a great deal has already been learned
through previous physiological and genetic studies of normal and disease conditions, primarily in humans and
rodents. Many of these studies have taken advantage of patients or laboratory animals with extremely impaired
metabolic responses. In these cases, errors in metabolic pathways result in severe deleterious consequences,
leading to morbidity and mortality. In nature, however, there is a second kind of extreme variation: there are
many cases where animals have adapted to extreme environments or extreme lifestyles through changes in
metabolic regulation. In these instances, the metabolic changes are adaptive, not pathological, meaning they
occur in such a way that the effects are not deleterious and/or other physiological changes occur to
compensate for any detrimental consequences. In principle, this provides an opportunity for identifying
resilience mechanisms that may have escaped notice through study of the circuits disrupted in disease.
However, to fully harness this natural variation for gene discovery, one wants to be able to compare metabolic
regulation in such animals with related organisms that have not undergone such extreme adaptation. Yet, in
many cases there is no closely related animal with a more “normal” metabolism for comparison. An important
exception is the cave-dwelling Mexican cave tetra, Astyanax mexicanus, which thrives under essentially
starvation conditions, and its river cousins who are of the same species. Together they offer a unique and
exciting opportunity to examine the metabolic adaption to an extreme living condition in an organism ripe for
genetic and genomic analysis. This proposal builds on published data showing that cavefish have evolved a
dramatically altered metabolism, including accumulation of high body fat levels and fatty livers, insulin
resistance and unstable blood glucose levels, without apparent adverse effects on their health. Use of state of
the art genomic, genetic and gene editing technologies now offers the possibility of identifying signaling
pathways that underlie starvation resistance and resilience mechanisms under extreme nutritional situations.
The proposal leverages the practical advantages of the model system to be amenable to comparative
approaches such as RNA-Seq, chromatin architecture analysis, mapping strategies such as QTL-analysis,
gene modification techniques such as CRISPR/Cas9, and novel transgenic lines, all combined with its unique
ecological adaptation scenario. This research proposal, therefore, aims to take advantage of this resource to
understand more fully the metabolic changes that allow the cavefish to survive in their bleak environment and
to start to dissect the regulatory changes that underlie the resilience mechanisms allowing these f...

## Key facts

- **NIH application ID:** 9999788
- **Project number:** 1DP2AG071466-01
- **Recipient organization:** STOWERS INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** Nicolas Rohner
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,475,000
- **Award type:** 1
- **Project period:** 2020-09-11 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999788

## Citation

> US National Institutes of Health, RePORTER application 9999788, Starvation resistance and resilience of metabolic dysfunction in cavefish (1DP2AG071466-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9999788. Licensed CC0.

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