A four-track perspective for bottom-up synthetic cells

Abstract

A crucial move for the development of the bottom-up synthetic biology (SB) branch took place about 20 years ago, when Jack W. Szostak, David Bartel and Pier Luigi Luisi coauthored a Nature paper entitled "Synthesizing Life" (Szostak et al., 2001), which can be considered a sort of foundational paper for (or even the manifesto of) the modern approaches for constructing living artificial cells from scratch. Possibly as a sign of the Zeitgeist, the article was published almost simultaneously to two other foundational papers in SB (Elowitz et al., 2000;Gardner et al., 2000).The very idea of synthesizing life-the Faustian dream of all times-is not new. Several (unsuccessful) attempts to build cell-like systems of minimal complexity fill the annals of science (Hanczyc, 2009). These attempts share a common anti-vitalistic viewpoint: synthesizing (cellular) life from scratch should be possible, and it would demonstrate that the biological phenomenology follows a "continuity principle" with respect to physics and chemistry. That is, life is an emergent property of some molecular systems characterized by a very peculiar type of structural and dynamical (self-) organization. However trivial and generally taken for granted by scientists, the emergence of life from inanimate matter has never been demonstrated experimentally and it is still one of the big targets in science.What is, then, the remarkable and novel element that has been put forward in the "Synthesizing Life" article, and that can be considered as a foundational concept for bottom-up approaches in SB? The Authors actually focused on the hypothetical construction of primitive cell (protocell) models, made of catalytically active RNAs (ribozymes) (Bartel and Szostak, 1993; Eckland et al., 1995), encapsulated inside fatty acid vesicles (Hargreaves and Deamer, 1978; Bachman et al., 1992;Walde et al., 1994). The claim is that such structures would display minimal life-like behavior (reproductive and potentially evolutive) if the intravesicle ribozymes catalyze their own replication and the production of membrane molecules at the expenses of certain precursors available in the environment. The whole process would lead to a spontaneous growth-division of protocells in an allegedly primitive Earth scenario.Leaving aside, for the moment, the mechanistic details and their plausibility, the fundamental and explicit message of that paper goes beyond the apparently narrow focus on the origin of life. To a closer inspection, in fact, the Authors put forward an operational methodology for the construction of chemical reacting systems that would show the difficult-to-define property of being alive just by fulfilling a specific structural and

Visioning synthetic futures for yeast research within the context of current global techno‐political trends

“…The SynCell2020/21 conference is a good example of the nascent synthetic cell community preparing for a multi-decade research programme that will require international collaborative links spanning the globe. SynCell2023 in Minneapolis will continue to advance this agenda bringing together the core organisations that have developed (Stano, 2021(Stano, , 2022. In this context, technologies and developments derived from advances in minimal genomes, neochromosomes and synthetic yeast genomes encompassing global collaborative efforts will be shared with these 'bigger picture' projects and ultimately contribute to a wider consortium focusing on a model-agnostic platform.…”

“…Fundamental research in yeast is central to setting the boundaries of what is known about cellular life and what can be imagined about its future potential in fully synthetic systems (Stano, 2021, 2022). In this context, technologies and developments derived from advances in minimal genomes, neochromosomes and synthetic yeast genomes encompassing global collaborative efforts will be shared with these ‘bigger picture’ projects and ultimately contribute to a wider consortium focusing on a model‐agnostic platform.…”

Advancing Biomimetic Functions of Synthetic Cells through Compartmentalized Cell-Free Protein Synthesis

“…1 The top-down approach involves modifying living cells to reduce their inherent complexity, 2 while the bottom-up approach aims to recreate essential features of living cells through engineering of synthetic building blocks. 3 This Review specifically focuses on the bottom-up approach. Despite the large variability in biological cells, in terms of form and function, all living cells contain at least three essential features.…”

Light energy transduction in liposome-based artificial cells

“…The goal of building cells from scratch has got increasing attention in Synthetic Biology ( Stano, 2022 ) as confirmed by the growing number of publications and scientific networks related to this topic ( Schwille et al, 2018 ; Frischmon et al, 2021 ; Staufer et al, 2021 ). Several simplified cell models which exhibit or mimic some characteristics of natural cells, have been successfully developed ( Rampioni et al, 2014 ; Cho and Lu, 2020 ; Gaut and Adamala, 2021 ; Ivanov et al, 2021 ).…”