# DNA Recorder: Living biosensor for arbitrary DNA

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $182,983

## Abstract

Project Summary
Recent decades have revealed the profound impacts that gut microbiota have on human
health. Far beyond being simply pathogenic vs benign, gut microbes impact a variety of
health and disease states, including metabolic, digestive, and mental health, as well as
propensity to cancer. Adding to the complexity, gut microbes can influence the
metabolism, and thereby action, of drugs developed to promote health and treat disease.
This suggests that many conditions would benefit from a more personalized treatment
plan that takes individual gut microbiota into account. Stratifying by microbial profile
may also benefit drug development, by removing a confounding variable in clinical trials.
The current standard method of measuring the gut microbiota is via fecal samples.
However, while convenient, inexpensive, and non-invasive, these samples do not
accurately reflect the details of gut communities. Up to a third of intestinal microbes can
be effectively absent from fecal samples, which also fail to preserve information about
spatial structure. Therefore, new measurement techniques are needed to more accurately
profile gut microbiota. Here, we will develop an innovative approach that uses living
biosensors to record extracellular DNA as they traverse the gut, preserving a record of
the internal microbial composition and spatial structure. This strategy relies on naturally
competent bacteria, which we recently used to detect DNA released from colorectal
tumors in vivo. The first two aims will develop complementary strategies to store
extracellular DNA, and the third will demonstrate them in mice. In Aim 1, we will store
snippets of environmental DNA in CRISPR arrays for later readout. This aim includes the
endogenous CRISPR-Cas system, as well as alternative systems that may be better suited
for the target DNA. In Aim 2, we will test the hypothesis that environmental DNA can
instead be stored by casposases, which could allow storage of longer snippets. These two
aims serve as alternative approaches for each other, and both approaches will also encode
bio-spatial information in the order of recorded DNA sequences. In Aim 3, we will
validate the gut DNA recorder in vivo using mouse models of dysbiosis. This work will
develop highly innovative approaches, with risk appropriate for this mechanism and
ameliorated by multiple alternatives. The result of this work will be a novel diagnostic
technique that can record and measure the microbiota across the entire intestinal tract,
with no invasive prodedures required.

## Key facts

- **NIH application ID:** 10871491
- **Project number:** 1R21EB035772-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Robert M Cooper
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $182,983
- **Award type:** 1
- **Project period:** 2024-08-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10871491

## Citation

> US National Institutes of Health, RePORTER application 10871491, DNA Recorder: Living biosensor for arbitrary DNA (1R21EB035772-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10871491. Licensed CC0.

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