CRISPRhistory | Reconstructing cellular histories with transcriptional recording

Summary
What are the main differences between a photograph and a video? Photographs record a single point in time and videos continuously record a sequence of events. While the content and interpretation of a photograph is heavily reliant on a single moment in time, a video is not. The tools that scientists have to understand the molecular and cellular world around them are most like film cameras – producing single snapshots to describe dynamic processes. Towards the goal of continuously recording molecular events within cells, my laboratory recently developed ‘transcriptional recording’, an approach that employs CRISPR spacer acquisition from RNA to capture and convert intracellular RNAs into DNA, permanently storing transcriptional information in the DNA of living cells. The newly acquired sequences serve as transcriptional records, which are retrievable via deep sequencing and can be leverage to reconstruct cellular histories. This technology provides an entirely new mode of interrogating dynamic biological and physiological processes and opens up numerous avenues for future work.

The overall goal of this proposal is to develop transcriptional recording sentinel cells with the capacity to continuously monitor biological and pathological processes within the mammalian gut. To achieve this goal, we will employ a variety of methods that include molecular and cellular biology, synthetic biology, protein engineering, bioinformatics, and mouse models. We will focus our efforts on improving the efficiency of transcriptional recording, combining transcriptional recording with biosensing gene circuits, and demonstrating that transcriptional recording sentinel cells facilitate interrogation of the mammalian gut environment and can be applied as a living diagnostic. In summary, this study lays the foundation for developing a fundamentally new approach to interrogating dynamic biological and pathological processes as well as engineering living diagnostics.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/851021
Start date: 01-12-2019
End date: 30-11-2024
Total budget - Public funding: 1 499 564,00 Euro - 1 499 564,00 Euro
Cordis data

Original description

What are the main differences between a photograph and a video? Photographs record a single point in time and videos continuously record a sequence of events. While the content and interpretation of a photograph is heavily reliant on a single moment in time, a video is not. The tools that scientists have to understand the molecular and cellular world around them are most like film cameras – producing single snapshots to describe dynamic processes. Towards the goal of continuously recording molecular events within cells, my laboratory recently developed ‘transcriptional recording’, an approach that employs CRISPR spacer acquisition from RNA to capture and convert intracellular RNAs into DNA, permanently storing transcriptional information in the DNA of living cells. The newly acquired sequences serve as transcriptional records, which are retrievable via deep sequencing and can be leverage to reconstruct cellular histories. This technology provides an entirely new mode of interrogating dynamic biological and physiological processes and opens up numerous avenues for future work.

The overall goal of this proposal is to develop transcriptional recording sentinel cells with the capacity to continuously monitor biological and pathological processes within the mammalian gut. To achieve this goal, we will employ a variety of methods that include molecular and cellular biology, synthetic biology, protein engineering, bioinformatics, and mouse models. We will focus our efforts on improving the efficiency of transcriptional recording, combining transcriptional recording with biosensing gene circuits, and demonstrating that transcriptional recording sentinel cells facilitate interrogation of the mammalian gut environment and can be applied as a living diagnostic. In summary, this study lays the foundation for developing a fundamentally new approach to interrogating dynamic biological and pathological processes as well as engineering living diagnostics.

Status

SIGNED

Call topic

ERC-2019-STG

Update Date

27-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.1. EXCELLENT SCIENCE - European Research Council (ERC)
ERC-2019
ERC-2019-STG