# Creating a niche for engineered live biotherapeutics

> **NIH NIH R35** · IOWA STATE UNIVERSITY · 2022 · $290,679

## Abstract

PROJECT SUMMARY
The long-term goal of this proposal is to improve outcomes of delivery of small molecules,
peptides, and proteins to the human gut by engineered live biotherapeutic bacteria. To
accomplish this, we will use two strategies to optimize biotherapeutic growth in the gut
environment. First, we will match prebiotic compounds (complex carbohydrates not digested by
the body) with heterologous expression of enzymes that allow cells to utilize these privileged
carbon sources. Second, we will create genome-scale libraries in our candidate biotherapeutics,
E. coli Nissle 1917 and Lactococcus lactis, to identify gene products that increase fitness in the
gut and gut-like environments. The methods will be tested in in vitro culture, small intestinal
organoid co-culture, and in vivo in the mouse gut to determine enrichment of the biotherapeutic
population, enhanced production of the therapeutic small molecule, peptide, or protein of
interest, and phenotypic outcome in systems of increasing verisimilitude to the human gut.

## Key facts

- **NIH application ID:** 10427447
- **Project number:** 5R35GM143074-02
- **Recipient organization:** IOWA STATE UNIVERSITY
- **Principal Investigator:** Thomas J Mansell
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $290,679
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10427447

## Citation

> US National Institutes of Health, RePORTER application 10427447, Creating a niche for engineered live biotherapeutics (5R35GM143074-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10427447. Licensed CC0.

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