# Research Resources for Model Amphibians

> **NIH NIH R24** · UNIVERSITY OF KENTUCKY · 2022 · $499,886

## Abstract

This application proposes to develop fundamental genomic and bioinformatic resources that will better enable
studies of the axolotl (Ambystoma mexicanum). The axolotl provides the best model for identifying mechanisms
of regeneration that can translate to humans. This is because it can regenerate multiple damaged body parts,
including whole limbs, spinal cord, and brain, and because it shares tetrapod biology with human. Understanding
how axolotls regenerate complex tissues may reveal mechanisms to activate stem cells within human tissues to
organize and reform damaged tissues. Beyond regeneration, the axolotl presents many untapped disease
models that were identified and rigorously examined with traditional developmental approaches before the
genetics/genomics era. With our recent development of the first chromosome-scale assembly of the axolotl
genome, these and new models that will be created in coming years through genome editing, can be advanced
for the first time to significantly impact biomedical research. However, to advance these models, improvements
of the genome assembly are needed along with new datasets to enable genome-wide studies of the large axolotl
genome. To accomplish these objectives, we propose three specific aims. In Aim 1, we will resolve inter- and
intra-specific variation within the current assembly and resolve complex repetitive regions that have hampered
the placement of ~6 Gb of the 32 Gb genome. Specifically, we will employ a powerful trio binning strategy that
takes advantage of long read sequencing of DNA from axolotl x tiger salamander (A. tigrinum) hybrids. This
approach leverages decades of experience in generating interspecific hybrids to resolve assembly gaps/errors
and accurately place gene models within their non-coding regulatory environments. Additionally, we will analyze
sequence data from 10 AGSC axolotls from branches of the pedigree that optimally sample laboratory genetic
diversity. In Aim 2, we will perform Chip-Seq to identify changes in histone post-translational modifications during
tail and limb regeneration. Characterization of epigenetic marks for embryo, larval, and adult models of
regeneration will provide new resources for regeneration research and advance community efforts in performing
genome wide studies. Aim 3 will address significant community needs, user-friendly access to large scale
genomic datasets and improvement of genomic and bioinformatic capabilities of investigators in the axolotl
community. Accomplishment of these aims will significantly advance axolotl as an animal model for biomedical
research.

## Key facts

- **NIH application ID:** 10408992
- **Project number:** 2R24OD010435-20A1
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Jeramiah James Smith
- **Activity code:** R24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $499,886
- **Award type:** 2
- **Project period:** 2001-10-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10408992

## Citation

> US National Institutes of Health, RePORTER application 10408992, Research Resources for Model Amphibians (2R24OD010435-20A1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10408992. Licensed CC0.

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