# Regulation of carbon utilization in gut-resident bacteria

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA BERKELEY · 2023 · $46,723

## Abstract

PROJECT SUMMARY - R35 PARENT GRANT
The microbiota of the mammalian gut is a complex community of individual strains shaped in part by microbial
competition over diet components. Despite computational analyses predicting enzymatic capacity of diverse
bacteria, this knowledge is not sufficient to determine how diet influences bacterial abundance in the gut. In
particular, little is known about regulation of carbon utilization enzymes in gut bacteria. Do they have
mechanisms similar to E. coli carbon catabolite repression to consume preferred nutrients sequentially? Or do
they consume all available nutrients simultaneously? How do these different strategies contribute to microbial
abundance in the gut? We have identified a mechanism resembling carbon catabolite repression in Collinsella
aerofaciens that may be a disadvantage when there is an abundance of secondary carbon source in the gut.
Our laboratory seeks to characterize regulatory mechanisms governing carbon consumption in Collinsella
species, in culture and in the mouse gut. Collinsella species are poorly studied Actinobacteria that are linked to
chronic human diseases including type 2 diabetes and atherosclerosis. We have studied a group of closely
related species and strains that vary in their regulation of carbon consumption. We will use this existing
variability and experimental evolution to identify a common pathway of carbon catabolite repression in these
bacteria. We will measure the heterogeneity of this pathway and related metabolic functions using single-cell
RNA-seq. Finally, we will characterize the impact of this regulation on bacterial growth and competition in the
mouse gut.
Together, this research will define regulatory pathways that contribute to advantageous strategies in the
complex nutrient environment of the mammalian intestine. Despite the vast number of correlative studies
implicating a role for the gut microbiome in human disease, there remains much to explore in identifying
bacterial metabolic pathways governing bacterial abundance and function in the gut. This gap limits both our
understanding of the basic biology of these community interactions as well as the ability to design effective
microbial therapeutics for human diseases characterized by complex microbial dysbiosis.

## Key facts

- **NIH application ID:** 10823904
- **Project number:** 3R35GM147512-02S2
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Ashley Robin Wolf
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $46,723
- **Award type:** 3
- **Project period:** 2022-09-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10823904

## Citation

> US National Institutes of Health, RePORTER application 10823904, Regulation of carbon utilization in gut-resident bacteria (3R35GM147512-02S2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10823904. Licensed CC0.

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