Roadmap to Building a Cell: An Evolutionary Approach.

Christophe Danelon,Zhanar Abil

doi:10.3389/fbioe.2020.00927

Abstract

Laboratory synthesis of an elementary biological cell from isolated components may aid in understanding of the fundamental principles of life and will provide a platform for a range of bioengineering and medical applications. In essence, building a cell consists in the integration of cellular modules into system’s level functionalities satisfying a definition of life. To achieve this goal, we propose in this perspective to undertake a semi-rational, system’s level evolutionary approach. The strategy would require iterative cycles of genetic integration of functional modules, diversification of hereditary information, compartmentalized gene expression, selection/screening, and possibly, assistance from open-ended evolution. We explore the underlying challenges to each of these steps and discuss possible solutions toward the bottom-up construction of an artificial living cell.

Highlights

All known life forms are composed of cells as the elementary unit
How practically the myriad of components will assemble into a functional cell remains a largely unexplored area. This perspective addresses this challenge by conceptualizing an evolutionary synthetic biology route
We propose to address these difficulties of building a synthetic cell by using a system’s level evolutionary approach (Figures 1C,D), which offers an achievable alternative to the traditional rational engineering strategy

Summary

INTRODUCTION

All known life forms are composed of cells as the elementary unit. the staggering complexity of even the simplest known cells is prohibitive to our understanding of the most basic principles of life. Building a biological cell from scratch, i.e., from a minimal set of loose components, such as in vitro synthesized or purified biomolecules, would serve as a forward engineering approach, illuminating the design principles of life (Elowitz and Lim, 2010). Some of life’s functionalities, such as self-organization, self-maintenance, and information continuity, have been extensively studied and attempts have been made to at least partially reproduce them in the laboratory (Caschera and Noireaux, 2014) Integration of these functionalities in a single synthetic cell still remains far out of reach (Caschera and Noireaux, 2014). A synthetic cell will require a functional integration of multiple modules, which implies further engineering of functional orthogonality, compatibility, and cross-regulation of parts This approach traditionally involves detailed analysis of individual modules and laborious finetuning processes to make the genetic circuits, pathways, and other complex networks to function as desired.

A SYSTEM’S LEVEL EVOLUTIONARY APPROACH

CONCLUSION