# High Resolution Characterization of Bacterial Epigenomes and Microbiome

> **NIH NIH R35** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $825,990

## Abstract

PROJECT SUMMARY/ABSTRACT
My long term goal is to comprehensively understand the diversity, heterogeneity and functions of bacterial
epigenomes both in terms of basic science and biomedical impact. In the bacterial world, methylated adenine
and cytosine residues was previously thought to be only associated with restriction-modification systems that
provide a defense mechanism against invading foreign genomes. However, increasing evidence supports that
they also play important roles in the regulation of cell cycle, gene expression, virulence, sporulation, biofilm
formation, microbe-host interaction and antibiotic resistance. Efficient and high resolution profiling of bacterial
DNA methylation events has not been possible until the advent of Single Molecule Real-Time (SMRT)
sequencing. This technique enabled us to characterize the first bacterial methylome at single nucleotide
resolution. A fast growing number of bacteria are being characterized, from which exciting discoveries have
been made. However, these studies have also revealed unexpected complexity and diversity in bacterial
methylomes, calling for the development new technologies, analytical and experimental methods in order to
more comprehensively understand bacterial epigenomes. In this R35 project, we will build on the progress we
have made in the past five years to further develop an integrated research program with a broader scope
integrating two ongoing focused R01 projects. The overarching theme is focused on the mapping,
characterization and exploitation of bacterial methylomes to better understand individual bacteria and
microbiome community. We will develop this research program along four complementary themes. First, to
more comprehensively map bacterial methylome, we will continue to innovate on technology development to
make significant improvements both in terms of in terms of completeness and resolution. Second, to better
elucidate epigenetic regulation in bacteria, we will combine computational and experimental approaches to
prioritize and functionally characterize specific methylation events across different bacterial organisms. Third,
to systematically expand bacterial methylome research from cultured individual bacteria to microbiome, we will
characterize bacterial epigenetics in response to different types of perturbations. Last, we will provide the
software we develop as an integrated package to ease broad usage, and organize relevant conference
tutorials to help the broader community. Combined together, we expect this project to provide broadly
applicable methods to the microbiology and microbiome community, and discover novel biological insights into
epigenetic regulation in individual bacteria and microbiome.

## Key facts

- **NIH application ID:** 10337240
- **Project number:** 5R35GM139655-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Gang Fang
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $825,990
- **Award type:** 5
- **Project period:** 2021-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10337240

## Citation

> US National Institutes of Health, RePORTER application 10337240, High Resolution Characterization of Bacterial Epigenomes and Microbiome (5R35GM139655-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10337240. Licensed CC0.

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