# Single-cell elucidation of transcriptional regulatory mechanisms that govern cell surface variation of the human symbiotic bacteria Bacteroidetes

> **NIH NIH F31** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $33,471

## Abstract

Project Summary and Abstract
Phase variation of gene expression enables bacteria to generate heterogenous populations and organize
communities that collectively can withstand diverse environmental perturbations. This discrete ON/OFF pattern
of gene expression occurs at multiple loci concurrently to create extensive phenotypic variation, but how
expression from multiple phase variable loci is coordinated is unknown. We developed a breakthrough single-
cell microfluidics technology to study phase variation at multiple loci directly, simultaneously, and over time to
track specialized bacterial sub-populations and learn fundamental principles determining their relative
abundances, rates of development, and interconnectedness. We learn these principles for Bacteroides fragilis,
a crucial human gut symbiote and master of phase variation. B. fragilis directly inhibits pathogens such as
Clostridium difficile and rapidly evolves a vast reservoir of mobile, phase variable antibiotic resistance genes.
Studying phase variation mechanisms in B. fragilis will enhance engineering of human microbiota and rational
design of symbiote-friendly antibiotics to limit evolution and subsequent mobilization of antibiotic-resistance
genes. We combine single-cell microfluidics with genomics and biochemistry to specifically dissect a two-part
regulatory system enabling coordinated phase variation: promoter inversion and termination control. To study
these fundamental principles governing phase variable gene expression, I will be trained primarily in genomics
and single-cell microfluidics by my co-mentors, Dr. Robert Landick and Dr. Ophelia Venturelli. Dr. Landick’s
decades of experience studying fundamental mechanisms of prokaryotic gene regulation combined with Dr.
Venturelli’s expertise in anaerobic bacteriology, engineering, and microfluidics provide me optimal training to
achieve my career goal. The state-of-the-art facilities and resources provided by UW-Madison and the
Departments of Biochemistry and Bacteriology provide me with the optimal environment in which I will carry out
this project.

## Key facts

- **NIH application ID:** 10464643
- **Project number:** 1F31GM142153-01A1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Johnson Jargese Saba
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $33,471
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464643

## Citation

> US National Institutes of Health, RePORTER application 10464643, Single-cell elucidation of transcriptional regulatory mechanisms that govern cell surface variation of the human symbiotic bacteria Bacteroidetes (1F31GM142153-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10464643. Licensed CC0.

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