Versioning biological cells for trustworthy cell engineering

Jonathan Tellechea-Luzardo,Leanne Hobbs,Elena Velázquez,Lenka Pelechova,Víctor De Lorenzo,Simon Woods,Natalio Krasnogor

doi:10.1038/s41467-022-28350-4

Jonathan Tellechea-Luzardo, Leanne Hobbs + Show 5 more

Open Access

https://doi.org/10.1038/s41467-022-28350-4

Copy DOI

Abstract

“Full-stack” biotechnology platforms for cell line (re)programming are on the horizon, thanks mostly to (a) advances in gene synthesis and editing techniques as well as (b) the growing integration of life science research with informatics, the internet of things and automation. These emerging platforms will accelerate the production and consumption of biological products. Hence, traceability, transparency, and—ultimately—trustworthiness is required from cradle to grave for engineered cell lines and their engineering processes. Here we report a cloud-based version control system for biotechnology that (a) keeps track and organizes the digital data produced during cell engineering and (b) molecularly links that data to the associated living samples. Barcoding protocols, based on standard genetic engineering methods, to molecularly link to the cloud-based version control system six species, including gram-negative and gram-positive bacteria as well as eukaryote cells, are shown. We argue that version control for cell engineering marks a significant step toward more open, reproducible, easier to trace and share, and more trustworthy engineering biology.

Highlights

“Full-stack” biotechnology platforms for cell lineprogramming are on the horizon, thanks mostly to (a) advances in gene synthesis and editing techniques as well as (b) the growing integration of life science research with informatics, the internet of things and automation
To demonstrate the wide applicability of CellRepo, we show how the platform—in conjunction with well-established peerreviewed protocols to genetically engineer various organisms— can be applied to six of the most important and diverse microbial species used in both academia and industry (Escherichia coli, Bacillus subtilis, Streptomyces albidoflavus, Pseudomonas putida, Saccharomyces cerevisiae and Komagataella phaffii—previously known as Pichia pastoris)
We postulate that adoption of CellRepo will improve:

Summary

Introduction

“Full-stack” biotechnology platforms for cell line (re)programming are on the horizon, thanks mostly to (a) advances in gene synthesis and editing techniques as well as (b) the growing integration of life science research with informatics, the internet of things and automation. Engineering biology is exploding with advances ranging from new genome editing tools[1], to genetically encodable materials for advanced sensing of cells physiological states, electrical fields and mechanical stresses[2,3], programmable and functional microbial-based living materials[4], environmental remediation and pollution control[5] to advanced in vivo data storage[6]. Engineering a “synthetic biology agent”[14] produces large quantities of information: published articles, protocols, notebooks, models, databases, sequencing and other types of data (e.g., metabolomics, proteomics, lipidomics, etc.) Combined, all these information sources may add up to terabytes of data but only a relatively small percentage of it is being made available when results are published in specialized outlets. It is clear that this gap in scientific practice requires a response on multiple fronts, to which this paper contributes in a number of practical ways with the introduction of CellRepo as a community resource

Methods

Results

Conclusion