# Translational control by nutrients

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2022 · $677,298

## Abstract

The ability to adapt to environmental challenges is critical for cellular and organismal function. A frequent
challenge is dehydration which increases osmotic pressure on the cells causing water loss and cell shrinkage.
Cells respond by accumulating organic osmolytes to accommodate decreases in cell volume and ionic strength
in a process called osmoadaptation. This cellular stress response is critical for survival of all organisms and
tissues. Defects in osmoadaptation induce a pro-inflammatory program that decreases cell survival and has
implications for multiple pathologies, including inflammatory bowel disease, diabetes, cancer and dry eye
syndrome. Diabetes associated hyperglycemic hyperosmolar syndrome (HHS) is life threatening. It is therefore
important to understand the molecular mechanisms of osmoadaptation. Our application focuses on the
regulation of protein synthesis during osmoadaptation, a critical process that is poorly understood. The overall
goal of this proposal is to develop a mechanistic, transcriptome-wide understanding of translation regulation
during osmoadaptation that will lead to development of therapeutics of diseases that cause decreased tissue
osmotolerance. We will examine the function of key regulators, including the amino transporter SNAT2 for
establishing osmoadaptive mRNA translation programs using Human Corneal Epithelial Cells (HCEs). Corneal
Epithelial cells are the cells in the eye that develop the pathology of dry eye syndrome in diabetes. To develop
a mechanistic, transcriptome-wide understanding of translation regulation during osmoadaptation we
characterize the translation landscape during osmoadaptation and define the regulatory RNA features that
control the changes in mRNA translation (Aim 1). We then focus on the interplay between translation
regulation, amino acid homeostasis and liquid-liquid phase separation (LLPS) of RNA binding proteins (RBPs)
during osmoadaptation and delineate how mTOR and SNAT2 activities affect the translation landscape in
response to hyperosmotic stress (Aim 2). Finally, we examine the function of RBPs that link LLPS and
translation regulation, by determining RNA binding patterns and LLPS for specific RBPs during
osmoadaptation (Aim 3).

## Key facts

- **NIH application ID:** 10528755
- **Project number:** 2R01DK060596-20
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** MARIA HATZOGLOU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $677,298
- **Award type:** 2
- **Project period:** 2002-03-15 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10528755

## Citation

> US National Institutes of Health, RePORTER application 10528755, Translational control by nutrients (2R01DK060596-20). Retrieved via AI Analytics 2026-06-10 from https://api.ai-analytics.org/grant/nih/10528755. Licensed CC0.

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