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Genomically minimal cells, such as JCVI-syn3.0 and JCVI-syn3A, offer an empowering framework to study relationships between genotype and phenotype. With a polygenic basis, the fundamental physiological process of cell division depends on multiple genes of known and unknown function in JCVI-syn3A. A physical description of cellular mechanics can further understanding of the contributions of genes to cell division in this genomically minimal context. We review current knowledge on genes in JCVI-syn3A contributing to two physical parameters relevant to cell division, namely, the surface-area-to-volume ratio and membrane curvature. This physical view of JCVI-syn3A may inform the attribution of gene functions and conserved processes in bacterial physiology, as well as whole-cell models and the engineering of synthetic cells.
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Meeting Proceedings from 4th Minimal Cell Workshop: Exploring JCVI Minimal Cell Fundamental Insights and Integrative Applications
The annual Minimal Cell Workshop, hosted by the J. Craig Venter Institute (JCVI), is an international virtual seminar that brings together over 80 academic, industrial, and government laboratories. Researchers use the JCVI’s minimal bacterial cell platform to explore the principles of cellular life and integrate new chemical pathways. Since its creation in 2016, this platform has fostered global collaborations. The fourth workshop featured 26 talks on ongoing research with minimal cell strains, including JCVI-syn1.0, JCVI-syn3.0, JCVI-syn3A, and JCVI-syn3B. Topics included innovative imaging techniques like super-resolution microscopy and cryotomography, DNA replication assays, and minimal cell division. New approaches for ATP synthesis and the role of moonlighting proteins were also discussed. JCVI-syn3B applications explored its potential in understanding persistent pathogens and as an anticancer therapeutic. The workshop encouraged sharing techniques for cell culture and genetic manipulation, fostering collaboration and advancing efforts to develop genome-scale algorithms for understanding and manipulating cellular functions.
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- PAR ID:
- 10630765
- Publisher / Repository:
- American Chemical Society
- Date Published:
- Journal Name:
- ACS Synthetic Biology
- Volume:
- 14
- Issue:
- 6
- ISSN:
- 2161-5063
- Page Range / eLocation ID:
- 1905 to 1911
- Subject(s) / Keyword(s):
- JCVI-syn3, minimal cell, synthetic cell
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Data from genomics, proteomics, structural biology and cryo-electron microscopy are integrated into a structural illustration of a cross section through an entire JCVI-syn3.0 minimal cell. The illustration is designed with several goals: to inspire excitement in science, to depict the underlying scientific results accurately, and to be feasible in traditional media. Design choices to achieve these goals include reduction of visual complexity with simplified representations, use of orthographic projection to retain scale relationships, and an approach to color that highlights functional compartments of the cell. Given that this simple cell provides an attractive laboratory for exploring the central processes needed for life, several functional narratives are included in the illustration, including division of the cell and the first depiction of an entire cellular proteome. The illustration lays the foundation for 3D molecular modeling of this cell.more » « less
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Abstract Minimal bacterial cells such as JCVI‐Syn3A provide a powerful system for uncovering the essential mechanisms of chromosome organization and segregation. Lacking canonical systems such as Min and ParABS, JCVI‐Syn3A relies primarily on structural maintenance of chromosomes (SMC) protein complexes for partitioning. Here, we investigate a four‐dimensional (4D; three spatial dimensions plus time) polymer‐based model of the JCVI‐Syn3A chromosome (543 kbp) that captures replication and partitioning dynamics across the full cell cycle. Our simulations reproduce chromosome segregation mediated by SMC‐driven loop extrusion and reveal how segregation depends on the number of SMC complexes, their translocation speed, and their dwell time on DNA. A systematic parameter scan shows that segregation is strongly predicted by the effective loop coverage, which represents the expected fraction of the chromosome extruded into loops. We generate contact maps for stationary‐phase cells to directly connect our simulations with 3C experiments, and for replicating chromosomes throughout the cell cycle to provide new, testable predictions for synchronized cell populations. Our results suggest that SMC protein complexes and topoisomerases can drive chromosome segregation in minimal cells without additional partitioning systems provided loop extrusion achieves sufficient genomic coverage.more » « less
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This article written in the popular journal The New Yorker takes a look at how the world's first minimal bacterial cell, which was made by a team from the J. Craig Venter Institute (JCVI) in 2016 has been used by both JCVI biologists and many other research groups to investigate the first principles of cellular life. The author, James Somers, writes much of the article using information obtained in his extended interview with JCVI scientist and minimal cell creator John Glass. The article introduces the public to ideas in synthetic biology, evolution, and the history of modern biology.more » « less
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null (Ed.)JCVI-syn3A is a genetically minimal bacterial cell, consisting of 493 genes and only a single 543 kbp circular chromosome. Syn3A’s genome and physical size are approximately one-tenth those of the model bacterial organism Escherichia coli ’s, and the corresponding reduction in complexity and scale provides a unique opportunity for whole-cell modeling. Previous work established genome-scale gene essentiality and proteomics data along with its essential metabolic network and a kinetic model of genetic information processing. In addition to that information, whole-cell, spatially-resolved kinetic models require cellular architecture, including spatial distributions of ribosomes and the circular chromosome’s configuration. We reconstruct cellular architectures of Syn3A cells at the single-cell level directly from cryo-electron tomograms, including the ribosome distributions. We present a method of generating self-avoiding circular chromosome configurations in a lattice model with a resolution of 11.8 bp per monomer on a 4 nm cubic lattice. Realizations of the chromosome configurations are constrained by the ribosomes and geometry reconstructed from the tomograms and include DNA loops suggested by experimental chromosome conformation capture (3C) maps. Using ensembles of simulated chromosome configurations we predict chromosome contact maps for Syn3A cells at resolutions of 250 bp and greater and compare them to the experimental maps. Additionally, the spatial distributions of ribosomes and the DNA-crowding resulting from the individual chromosome configurations can be used to identify macromolecular structures formed from ribosomes and DNA, such as polysomes and expressomes.more » « less
- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.1021/acssynbio.5c00159
