# Ribosomes and Regeneration: Defining the Role of Protein Synthesis in Tissue Development, Homeostasis and Repair.

> **NIH NIH K99** · STANFORD UNIVERSITY · 2020 · $111,916

## Abstract

PROJECT SUMMARY/ABSTRACT
Translation has emerged as a new and important layer of regulation at the last step in the journey from gene to
gene product. This regulation is conferred in part through the activity of specialized ribosomes which vary in their
complement of ribosomal proteins and have the capacity to selectively translate specific subsets of mRNAs.
While this mechanism may offer cells an unparalleled ability to rapidly adjust protein output, the extent and impact
of ribosome-mediated translational regulation has not yet been addressed in terminally differentiated cells and
tissues or at the organismal level. My preliminary studies demonstrate that translational regulation may be of
particular importance in promoting tissue regeneration in the axolotl - a species of highly regenerative
salamander. Using axolotl limb amputation as a model, I demonstrate that unlike in mammals, severe injury in
this species triggers a rapid translational response which selectively targets translation of ribosomal proteins. In
this proposal I examine the role of regulated protein synthesis in the axolotl and mouse; I establish the role of
specialized ribosomes in the process of axolotl limb regeneration and I extend the scope of this research to
murine chondrocytes and a novel human cartilage organoid system, in order to define the role of specialized
ribosomes in the development, regeneration and repair of vertebrate tissues. The long-term goal of this work is
to utilize in vitro and in vivo models, including micromass murine chondrocyte culture and human cartilage
organoids, genetic modeling in mice and regeneration modeling in axolotls, coupled with state-of-the-art mass
spectrometry and ribosome/polysome profiling methods to define the role of ribosome-mediated translational
regulation in tissue development and disease and to identify new genes and factors with therapeutic potential in
tissue regeneration, with a particular emphasis on cartilage health. The research proposed in this application will
be carried out within the highly collaborative environment of Stanford University and supported by a
multidisciplinary advisory committee with expertise in translation control, glycobiology, axolotl regeneration and
stem cell differentiation. Upon completion of the K99 phase, the candidate’s goals are to continue this work as
an independent investigator in an academic research setting.

## Key facts

- **NIH application ID:** 10003375
- **Project number:** 5K99HD099787-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Olena Zhulyn
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $111,916
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003375

## Citation

> US National Institutes of Health, RePORTER application 10003375, Ribosomes and Regeneration: Defining the Role of Protein Synthesis in Tissue Development, Homeostasis and Repair. (5K99HD099787-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10003375. Licensed CC0.

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