# Deep cell history tracking: engineering cells that write their detailed life stories into their DNA to study DNA damage

> **NIH NIH R00** · RICE UNIVERSITY · 2024 · $249,000

## Abstract

Project Summary
DNA recording is a recently developed technology that allows cellular signaling events of interest to be followed
over time without removing cells from their physiological context. During a DNA recording experiment, genetically
engineered cells expressing the DNA recorder acquire mutations at a “recording locus” as the result of transient
cellular events, without perturbing their normal phenotype. At the end of the experiment, once their eventual
phenotype is known, cells can be collected and their histories determined by sequencing the recording locus.
The work proposed here will lead to a DNA recorder that is not limited, as current technology is, to recording one
or two cellular events per experiment, but can record dozens of events in parallel, allowing an unbiased
examination of cell history in any context compatible with genetically engineered cells. In this project, the new
DNA recorder will be used to study long-term effects for a cell of experiencing significant spontaneous DNA
damage. Although DNA damage is very well-studied, it has not previously been possible to follow the rare cells
that experience significant spontaneous damage, especially in an in vivo mammalian context. The new DNA
recorder will be developed in stages: First, intracellular recording machinery, based on a pre-existing recorder,
will be created for a small number of cellular events associated with the DNA damage response. Next, the fidelity
of this new recording machinery will be extensively validated in cultured cells and cancer xenografts. Finally, a
new recording architecture will be developed and validated, before being introduced into a transgenic mouse to
identify how spontaneous DNA damage affects cell fate determination during normal development.

## Key facts

- **NIH application ID:** 10913635
- **Project number:** 5R00GM140254-04
- **Recipient organization:** RICE UNIVERSITY
- **Principal Investigator:** Theresa Berens Loveless
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2021-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10913635

## Citation

> US National Institutes of Health, RePORTER application 10913635, Deep cell history tracking: engineering cells that write their detailed life stories into their DNA to study DNA damage (5R00GM140254-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10913635. Licensed CC0.

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