# Co-translational Regulation in the Vasculature of Organ Systems with Aging

> **NIH NIH R21** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2023 · $239,850

## Abstract

Project Summary/Abstract
The production of functional proteins is a multistep process whereby newly synthesized
polypeptides are enzymatically processed, folded, and assembled into oligomeric complexes. Key
maturation processes occur co-translationally by coupling mRNA translation and nascent protein
maturation on the ribosomes, assisted by a network of regulatory proteins. Despite decades of
basic research, our understanding of co-translational processes is shaped predominantly by
genetic manipulations in prokaryotic and eukaryotic cell models, but limited data exists in cells
from intact mammalian physiological systems. To overcome this hurdle, this project aims to
develop a comprehensive understanding of co-translational regulation of nascent proteins as they
reach their functional state within the angiogenic signaling pathways of the endothelium in the
heart during aging. We have recently developed an approach and tested the potential for
simultaneous isolation of proteins present within the actively translating polyribosome/mRNA
complexes within the endothelium of the heart. State-of-the-art multiplex labelling and
quantification of these proteins has permitted the identification of concordant and discordant
regulated cell-specific pathways based on actively translating mRNA and protein profiles
associated with the endothelial stress. Leveraging this innovative advancement in “functional co-
translatomics”, we aim to study the changes in co-translational complexes within endothelial cell
angiogenic ligand-receptor and cell-cell interaction signaling networks within the aging heart. In
Aim 1
, we will define changes in the co-translational regulation of concordantly regulated
angiogenic signaling pathways during neonatal and adult life with aging and gender. In
Aim 2
, we
will define the post-translational modifications of proteins within discordantly regulated angiogenic
signaling pathways which may contribute to the impairment angiogenesis in the heart during
aging. Ultimately this knowledge could aid in the development of more effective means for
diagnosing and treating the impairment of angiogenesis that occurs with aging and predisposes
the heart to cardiovascular disease and injury.

## Key facts

- **NIH application ID:** 10738940
- **Project number:** 1R21AG080316-01A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** PAUL H GOLDSPINK
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $239,850
- **Award type:** 1
- **Project period:** 2023-08-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10738940

## Citation

> US National Institutes of Health, RePORTER application 10738940, Co-translational Regulation in the Vasculature of Organ Systems with Aging (1R21AG080316-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10738940. Licensed CC0.

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