# Integrative Approach To Study Mitochondrial Aminoacyl-tRNA Synthetase Disorders

> **NIH NIH K08** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $165,240

## Abstract

PROJECT SUMMARY/ABSTRACT
CANDIDATE. Dr. Webb has drawn on her academic achievement and diverse training and experience in
clinical and basic science to develop an independent research program. She has developed laboratory skills in
molecular and cellular biology and has acquired computational skills in bioinformatics and systems biology.
Additionally, her clinical training in Medical Genetics provides her with a strong background in inherited
metabolic diseases. Recognition of Dr. Webb's potential as an investigator is reflected in her current
appointment of Assistant Professor (tenure-track position, Investigator Track) in the Departments of Genetics
and Genomic Sciences (primary) and Pediatrics (secondary) at the Icahn School of Medicine at Mount Sinai.
She has been allocated >75% protected research time. Dr. Webb's accomplishments include several first-
author publications and additional co-authored manuscripts in high quality journals.
CAREER DEVELOPMENT. Dr. Webb's overall long-term career goal is to lead a meaningful and sustainable
research program that will allow her to remain a well-established and independent investigator in the fields of
metabolism, developmental genetics, and systems biology. These goals will be accomplished through the
mentorship, collaboration, and didactic mechanisms outlined in this application.
INSTITUTIONAL ENVIRONMENT. The Department of Genetics and Genomic Sciences and the Icahn
Institute for Genomics and Multiscale Biology at the Icahn School of Medicine at Mount Sinai is the ideal
setting for carrying out the work described in this application. Faculty in the Department are experts in the
identification, treatment, and study of inborn errors of metabolism. Additionally, members of the Icahn Institute
are world-renown in the ability to use systems biology and computational techniques to study disease.
RESEARCH PROJECT. Mitochondrial aminoacyl-tRNA synthetases (mt-ARSs) are essential for protein
synthesis in mitochondria, and disruption of mt-ARS function represents a new class of mitochondrial disease.
A novel disorder caused by recessive, single nucleotide variants in methionyl-tRNA synthetase 2 (MARS2)
associated with developmental delay, growth failure, and sensorineural hearing loss has been identified by the
candidate. The proposed project will utilize an integrative approach, combining both wet-laboratory and in
silico techniques, to further study mt-ARS disorders. Pathogenic variants in MARS2 will be further
characterized biochemically by assessing aminoacylation activity, mitochondrial protein synthesis, and
mitochondrial oxygen consumption. To better understand the variable phenotypes and tissue specificity of
different mt-ARS disorders, an in vitro model system of several mt-ARS disorders will be developed using
CRISPR/Cas9 technologies. RNA-seq data will be generated and network analysis will be completed to
identify key drivers and developmental pathways involved in mt-ARS disorders.

## Key facts

- **NIH application ID:** 9938585
- **Project number:** 5K08HD086827-05
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Bryn D Webb
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $165,240
- **Award type:** 5
- **Project period:** 2016-09-20 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9938585

## Citation

> US National Institutes of Health, RePORTER application 9938585, Integrative Approach To Study Mitochondrial Aminoacyl-tRNA Synthetase Disorders (5K08HD086827-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9938585. Licensed CC0.

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