# Translational Control: Discovery and Mechanisms

> **NIH NIH R35** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2024 · $222,251

## Abstract

Andrei A. Korostelev
PROJECT SUMMARY
Ribosomes are a central hub for controlling gene expression. They not only synthesize proteins, but also regulate
bacterial stress responses, human neurodevelopment and synaptic plasticity. Understanding how ribosomes
control gene expression requires high-resolution structural and accurate biochemical characterization of
ribosome dynamics and interactions, both in vitro and in complex cellular environments. We are uniquely
positioned to address these key challenges by investigating the following questions:
 How do ribosomes regulate bacterial stress responses? In bacteria, ribosomes sense cellular stress via
several pathways, which control the transcriptional adaptation to stress. The direct and indirect pathways that
couple translation with transcription are promising antibiotic targets. We will dissect the structural and cellular
mechanisms of using novel biochemical approaches and ensemble cryo-EM.
 How do ribosomes rapidly and accurately synthesize proteins? Translation is a major pathway for
sensing problematic mRNAs in eukaryotes, and dysregulation of stress-response mechanisms leads to disease.
To determine how the ribosome recognizes dysfunctional mRNAs with premature nonsense codons, we will use
cellular, biochemical and structural (time-resolved cryo-EM) methods to visualize ribosome interactions with
problematic mRNAs.
 How does translation regulate neurodevelopment and neuroplasticity and contribute to neurological
disorders? Translation regulation in neurons is essential for neurodevelopment, memory consolidation, and
learning, whereas translation dysregulation drives neurological diseases, such as amyotrophic lateral sclerosis.
The synaptic proteome—far from the nucleus—is controlled by local translation and requires brain-specific
translation factors and auxiliary proteins. To elucidate the molecular mechanisms of neuronal translation
regulation, we will use genetic, biochemical, and structural approaches, including cellular EM at Ångström-level
detail in functional neurons.

## Key facts

- **NIH application ID:** 11100797
- **Project number:** 3R35GM127094-07S1
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Andrei Korostelev
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $222,251
- **Award type:** 3
- **Project period:** 2018-05-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11100797

## Citation

> US National Institutes of Health, RePORTER application 11100797, Translational Control: Discovery and Mechanisms (3R35GM127094-07S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11100797. Licensed CC0.

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