# Molecular recording to predict cell fate decisions and animal behavior

> **NIH NIH RF1** · WASHINGTON UNIVERSITY · 2021 · $3,693,282

## Abstract

Abstract
 The brain is remarkably complex, and our understanding of this organ is still in its infancy. Many
fundamental questions about brain development and function remain. Single cell genomics promises new ways
to answer these questions, but nearly all single-cell methods share shortcoming – cells are destroyed when their
molecular states are measured. This “destruction upon observation” makes it impossible to correlate molecular
events that have occurred in the past with the final outcomes: if you destroy an intermediate progenitor in the
brain to profile its epigenome, you have no way to know what cell fate the progenitor would have adopted.
Likewise, profiling an animal after an experience is going to conflate the molecular consequences of the
experience with any molecular predispositions that were there before exposure. And if you profile before the
experience, you have no way of know of the animal's outcome – e.g. if the animal would have been a learner or
not. This shortcoming is inherent to nearly all existing genomic methods and impedes a wide variety of interesting
analyses. We have recently developed a platform technology, single-cell `Calling Cards' (CC) that uses
transposons to capture molecular events at one instant in time and then read them out at a later time with single
cell resolution. We now propose to build upon this foundation to develop a robust, easy to use technology
platform to record molecular events at single cell resolution in the mouse brain and connect them with cell fate
decision, behavioral outcomes, neuronal activity profiles, and anatomical location. We will develop a set of widely
applicable reagents and methods, apply them to a series of high-impact “test cases” to demonstrate their utility,
and rapidly distribute them to the broader community.

## Key facts

- **NIH application ID:** 10260139
- **Project number:** 1RF1MH126723-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** JOSEPH D DOUGHERTY
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $3,693,282
- **Award type:** 1
- **Project period:** 2021-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10260139

## Citation

> US National Institutes of Health, RePORTER application 10260139, Molecular recording to predict cell fate decisions and animal behavior (1RF1MH126723-01). Retrieved via AI Analytics 2026-08-11 from https://api.ai-analytics.org/grant/nih/10260139. Licensed CC0.

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