# Mapping cellular communication at single-cell resolution through novel CRISPR systems

> **NIH NIH R35** · J. DAVID GLADSTONE INSTITUTES · 2021 · $472,500

## Abstract

Project Summary/Abstract
Mapping cellular communication at single-cell resolution through novel CRISPR systems
The Fellmann lab focuses on decoding principles of cellular signaling in disease progression and therapy, and
pioneering of CRISPR-Cas and RNA interference (RNAi) systems. For over a decade, my research has centered
on better understanding RNA-guided immune systems and establishing innovative strategies to dissect disease,
many of which have found broad application among the scientific community. My lab currently studies the
interplay between Cas enzymes and DNA repair pathways to develop novel approaches for genome editing and
precision medicine. We apply these quantitative, high-throughput methods to study the plasticity of signaling
networks in health and disease, with the goal of translating insights into breakthrough therapies for patients.
A persisting challenge in biology is recording molecular information in a cell-specific manner without disrupting
the system under study. To overcome this, we propose transformative CRISPR platforms to track host-pathogen
interactions and map pathway deregulation in human disease. The approaches rest on the development of Cas9
and guide RNA systems that are responsive to 1) pathogen-specific proteases (“ProCas9s”) or 2) mammalian
cell-signaling events (“CRISPR-capture”), thereby enabling the recording of a cell’s history by inscribing marks
at predetermined loci in the genome. As rapid response to emerging viral threats, we will develop a ProCas9
that can autonomously record SARS-CoV-2 infections and label respective cells. We will use this strategy to
dissect long-term consequences of viral infection in cardiomyocytes. To enable general mapping of cellular
communication, we propose a novel data recording methodology termed CRISPR-capture that places the
expression of sgRNAs under the control of RNA polymerase II promoters, rather than the conventionally used
RNA Pol-III promoters. Since mammalian signaling outputs are largely based on transcription factors regulating
Pol-II promoters, CRISPR-capture tunes Cas activity to a cell’s state, providing the unique ability to map cellular
signaling at single-cell resolution and monitor key biological events over the lifetime of a cell for the first time.
Ultimately, we will leverage CRISPR-capture to monitor individual cells in four dimensions (space-time) during
disease progression and treatment, to uncover organizational principles of tissue heterogeneity and establish
new therapeutic strategies for patients. My multidisciplinary training in genome editing with Dr. Jennifer Doudna
(University of California, Berkeley), functional genomics with Dr. Scott Lowe (Cold Spring Harbor Laboratory),
and in-vivo animal models of human disease, allows me to bridge fundamental biology and patient-centered
research. Moreover, my experience as co-founder and Chief Scientific Officer of a successful start-up company
taught me invaluable lessons that will serve me wel...

## Key facts

- **NIH application ID:** 10277350
- **Project number:** 1R35GM143124-01
- **Recipient organization:** J. DAVID GLADSTONE INSTITUTES
- **Principal Investigator:** Christof Fellmann
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $472,500
- **Award type:** 1
- **Project period:** 2021-09-18 → 2022-08-21

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10277350

## Citation

> US National Institutes of Health, RePORTER application 10277350, Mapping cellular communication at single-cell resolution through novel CRISPR systems (1R35GM143124-01). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10277350. Licensed CC0.

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