# Systematic Discovery and Analysis of Small Proteins and Small ORFs in Mycobacteria

> **NIH NIH R01** · WADSWORTH CENTER · 2021 · $8,913

## Abstract

The last few decades have seen the birth and maturation of the field of Molecular Biology. Initially, mutant
genes were focal points of genome exploration. Now, entire genomes are routinely sequenced, and the
resident genes are automatically identified by annotation algorithms. Alternatively, proteomic approaches
prepare proteolytic peptides of whole-cell extracts for analysis by mass spectrometry. Each of these
approaches are strongly biased for large genes: large genes are frequent targets for mutation, long-open-
reading frames are easily discerned in genomic sequence, and large proteins generate many peptides
for mass spectrometry identification. This unintended bias has also created a large gap in our
understanding of molecular biology.
Recent work in eukaryotes and prokaryotes alike have uncovered multitudes of small genes or their
encoded proteins. The numbers of small proteins (considered as 50 aa or less) rival that of traditionally
large proteins, yet only a handful have been ascribed a function. The goal of this proposal is to propel
this nascent field forward by facilitating both small protein discovery and functional characterization. We
will develop and apply our small protein approaches in mycobacteria. Mycobacteria offer many
advantages for small protein study. Foremost is that they express >1000 small proteins in standard
conditions.
The goal of this supplement is to support an outstanding undergraduate student, Lauren Fox, who aspires
to be a research scientist, with direct hands-on laboratory research experience. Lauren will focus on
dissecting the mechanism of regulation mediated by a unique set of sproteins involved in cysteine
homeostasis. She will learn new technical and analytical skills, and develop a greater understanding of
what it takes to be a research scientist. Involvement in the Wadsworth summer research program for
undergraduates will further expose Lauren to potential careers in science, future mentors and new friends
and colleagues.

## Key facts

- **NIH application ID:** 10388045
- **Project number:** 3R01GM139277-01S1
- **Recipient organization:** WADSWORTH CENTER
- **Principal Investigator:** KEITH M DERBYSHIRE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $8,913
- **Award type:** 3
- **Project period:** 2020-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10388045

## Citation

> US National Institutes of Health, RePORTER application 10388045, Systematic Discovery and Analysis of Small Proteins and Small ORFs in Mycobacteria (3R01GM139277-01S1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10388045. Licensed CC0.

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