Towards a synthetic cell cycle

Olivi, Lorenzo; Berger, Mareike; Creyghton, Ramon; Franceschi, Nicola De; Dekker, Cees; Mulder, Bela M.; Claassens, Nico J.; Wolde, Pieter Rein ten; Oost, John van der

doi:10.1038/s41467-021-24772-8

Cited by 68 publications

(88 citation statements)

References 122 publications

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“…Such units need molecular systems that link the functional parts of a synthetic cell to a decoding mechanism that reads the genetic instructions required to autocatalytically build a new cell. They also require a molecular module that copies and reinserts a transcript of the (genetic) instruction into the synthetic daughter cell ( Olivi et al, 2021 ). This is the logical basis of self-reproduction.…”

Section: Recent Research Directions and Bottlenecksmentioning

confidence: 99%

Building a community to engineer synthetic cells and organelles from the bottom-up

Staufer

Lora

Bailoni

et al. 2021

eLife

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Employing concepts from physics, chemistry and bioengineering, 'learning-by-building' approaches are becoming increasingly popular in the life sciences, especially with researchers who are attempting to engineer cellular life from scratch. The SynCell2020/21 conference brought together researchers from different disciplines to highlight progress in this field, including areas where synthetic cells are having socioeconomic and technological impact. Conference participants also identified the challenges involved in designing, manipulating and creating synthetic cells with hierarchical organization and function. A key conclusion is the need to build an international and interdisciplinary research community through enhanced communication, resource-sharing, and educational initiatives.

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Section: Recent Research Directions and Bottlenecksmentioning

confidence: 99%

Building a community to engineer synthetic cells and organelles from the bottom-up

Staufer

Lora

Bailoni

et al. 2021

eLife

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“…These not only require a mechanism to copy the cellular architecture itself but also functionalities that allow for the copying of (genetic) information specifying cellular structure and function. Implementation of such cell-like entities requires molecular systems engineering solutions that link the (i) functional parts of a synthetic cell to (ii) a decoding mechanism that reads the genetic instructions required to autocatalytically build a new cell and (iii) a molecular module that copies and reinserts a transcript of the (genetic) instruction into the synthetic daughter cell 32 . This is the logical basis of self-reproduction.…”

Section: Recent Research Directions and Bottlenecksmentioning

confidence: 99%

Building a community to engineer synthetic cells and organelles from the bottom-up

Staufer

Lora

Bailoni³

et al. 2021

Preprint

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Empowered by emerging concepts from physics, chemistry, and bioengineering, learning-by-building approaches have found increasing application in the life sciences. Particularly, they are directed to tackle the overarching goal of engineering cellular life from scratch. The SynCell2020/21 conference brought together a diverse group of researchers to share progress and chart the course of this field. Participants identified key steps to design, manipulate, and create cell-like entities, especially those with hierarchical organization and function. This article highlights achievements in the field, including areas where synthetic cells are having socioeconomic and technological impact. Guided by input from early-career researchers, we identify challenges and opportunities for basic science and technological applications of synthetic cells. A key conclusion is the need to build an integrated research community through enhanced communication, resource-sharing, and educational initiatives. Development of an international and interdisciplinary community will enable transformative outcomes and attract the brightest minds to contribute to the field.

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“…A bottom-up assembled artificial cell should possess the ability to proliferate and evolve, which entails growth, division and information distribution. [1] The reconstitution of cell division has therefore gained growing interest. [1, 2, 3] A variety of strategies have been developed to divide lipid vesicles as synthetic cellular compartments.…”

Section: Introductionmentioning

confidence: 99%

“…[1] The reconstitution of cell division has therefore gained growing interest. [1, 2, 3] A variety of strategies have been developed to divide lipid vesicles as synthetic cellular compartments. [4, 5, 6, 7, 8, 9] Some have also succeeded in encapsulating DNA or RNA inside dividing vesicles,[4, 10, 11] however, information was distributed by random partitioning only.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, there is an undeniable call for a controlled DNA segregation module in artificial cellular systems. [1] The natural machinery for DNA segregation, namely the eukaryotic mitotic spindle or the bacterial Par system, are, for now, too intricate to be reconstituted and coordinated in a synthetic cell. [1, 12] Yet entropy-driven segregation of dense polymers in confinement, which is biologically relevant e.g.…”

Section: Introductionmentioning

confidence: 99%

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A DNA segregation module for synthetic cells

Tran

Chatterjee

Dreher

et al. 2022

Preprint

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The bottom-up construction of an artificial cell requires the realization of synthetic cell division. Significant progress has been made towards reliable compartment division, yet mechanisms to segregate the DNA-encoded informational content are still in their infancy. Herein, droplets of DNA Y-motifs are formed by liquid-liquid phase separation (LLPS). Entropy-driven DNA droplet segregation is obtained by cleaving the linking component between two populations of DNA Y-motifs. In addition to enzymatic cleavage, photolabile sites are introduced for spatio-temporally controlled DNA segregation in bulk as well as in cell-sized water-in-oil droplets and giant unilamellar lipid vesicles (GUVs). Notably, the segregation process is slower in confinement than in bulk. The ionic strength of the solution and the nucleobase sequences are employed to regulate the segregation dynamics. The experimental results are corroborated in a lattice-based theoretical model which mimics the interactions between the DNA Y-motif populations. Altogether, engineered DNA droplets, reconstituted in GUVs, could represent a strategy towards an entropy-driven DNA segregation module within bottom-up assembled synthetic cells.Table of ContentsAn entropy-driven DNA segregation module for bottom-up assembled synthetic cells is realized. It is based on DNA droplets that are engineered to segregate upon enzymatic or photocleavage inside giant unilamellar lipid vesicles (GUVs). The segregation kinetics is altered by the confinement, as confirmed by lattice-based numerical simulations. DNA segregation is further controlled by temperature, ionic strengths and nucleobase sequence.

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Towards a synthetic cell cycle

Cited by 68 publications

References 122 publications

Building a community to engineer synthetic cells and organelles from the bottom-up

Building a community to engineer synthetic cells and organelles from the bottom-up

Building a community to engineer synthetic cells and organelles from the bottom-up

A DNA segregation module for synthetic cells

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