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ABSTRACT Many microscopic images and simulations of cells give results in different kinds of formats, making it difficult for people lacking computational skills to visualize and interact with them. Minecraft—known for its three-dimensional, open-world, voxel-based environment—offers a unique solution by allowing the direct insertion of voxel-based cellular structures from light microscopy and simulations into its worlds without modification. This integration enables Minecraft players to explore the ultrastructure of cells in a highly immersive and interactive environment. Here, we demonstrate several workflows that can convert images and simulation results into Minecraft worlds. Using the workflows, students can easily import and interact with a variety of cellular content, including bacteria, yeast, and cancer cells. This approach not only opens new avenues for science education but also demonstrates the potential of combining scientific visualization with interactive gaming platforms for facilitating research and improving appreciation of cellular structure for a broad audience. 

Abstract Possessing only essential genes, a minimal cell can reveal mechanisms and processes that are critical for the persistence and stability of life^1,2. Here we report on how an engineered minimal cell^3,4contends with the forces of evolution compared with theMycoplasma mycoidesnon-minimal cell from which it was synthetically derived. Mutation rates were the highest among all reported bacteria, but were not affected by genome minimization. Genome streamlining was costly, leading to a decrease in fitness of greater than 50%, but this deficit was regained during 2,000 generations of evolution. Despite selection acting on distinct genetic targets, increases in the maximum growth rate of the synthetic cells were comparable. Moreover, when performance was assessed by relative fitness, the minimal cell evolved 39% faster than the non-minimal cell. The only apparent constraint involved the evolution of cell size. The size of the non-minimal cell increased by 80%, whereas the minimal cell remained the same. This pattern reflected epistatic effects of mutations inftsZ, which encodes a tubulin-homologue protein that regulates cell division and morphology^5,6. Our findings demonstrate that natural selection can rapidly increase the fitness of one of the simplest autonomously growing organisms. Understanding how species with small genomes overcome evolutionary challenges provides critical insights into the persistence of host-associated endosymbionts, the stability of streamlined chassis for biotechnology and the targeted refinement of synthetically engineered cells^2,7–9. 

All known life is homochiral. DNA and RNA are made from “righthanded” nucleotides, and proteins are made from “left-handed” amino acids. Driven by curiosity and plausible applications, some researchers had begun work toward creating lifeforms composed entirely of mirror-image biological molecules. Such mirror organisms would constitute a radical departure from known life, and their creation warrants careful consideration. The capability to create mirror life is likely at least a decade away and would require large investments and major technical advances; we thus have an opportunity to consider and preempt risks before they are realized. Here, we draw on an indepth analysis of current technical barriers, how they might be eroded by technological progress, and what we deem to be unprecedented and largely overlooked risks. We call for broader discussion among the global research community, policy-makers, research funders, industry, civil society, and the public to chart an appropriate path forward. 

The bacterial strain JCVI-syn3.0 stands as the first example of a living organism with a minimized synthetic genome, derived from the Mycoplasma mycoides genome and chemically synthesized in vitro. Here, we report the experimental evolution of a syn3.0- derived strain. Ten independent replicates were evolved for several hundred generations, leading to growth rate improvements of > 15%. Endpoint strains possessed an average of 8 mutations composed of indels and SNPs, with a pronounced C/G- > A/T transversion bias. Multiple genes were repeated mutational targets across the independent lineages, including phase variable lipoprotein activation, 5 distinct; nonsynonymous substitutions in the same membrane transporter protein, and inactivation of an uncharacterized gene. Transcriptomic analysis revealed an overall tradeoff reflected in upregulated ribosomal proteins and downregulated DNA and RNA related proteins during adaptation. This work establishes the suitability of synthetic, minimal strains for laboratory evolution, providing a means to optimize strain growth characteristics and elucidate gene functionality. 

Computational models of cells cannot be considered complete unless they include the most fundamental process of life, the replication and inheritance of genetic material. By creating a computational framework to model systems of replicating bacterial chromosomes as polymers at 10 bp resolution with Brownian dynamics, we investigate changes in chromosome organization during replication and extend the applicability of an existing whole-cell model (WCM) for a genetically minimal bacterium, JCVI-syn3A, to the entire cell-cycle. To achieve cell-scale chromosome structures that are realistic, we model the chromosome as a self-avoiding homopolymer with bending and torsional stiffnesses that capture the essential mechanical properties of dsDNA in Syn3A. In addition, the conformations of the circular DNA must avoid overlapping with ribosomes identitied in cryo-electron tomograms. While Syn3A lacks the complex regulatory systems known to orchestrate chromosome segregation in other bacteria, its minimized genome retains essential loop-extruding structural maintenance of chromosomes (SMC) protein complexes (SMC-scpAB) and topoisomerases. Through implementing the effects of these proteins in our simulations of replicating chromosomes, we find that they alone are sufficient for simultaneous chromosome segregation across all generations within nested theta structures. This supports previous studies suggesting loop-extrusion serves as a near-universal mechanism for chromosome organization within bacterial and eukaryotic cells. Furthermore, we analyze ribosome diffusion under the influence of the chromosome and calculatein silicochromosome contact maps that capture inter-daughter interactions. Finally, we present a methodology to map the polymer model of the chromosome to a Martini coarse-grained representation to prepare molecular dynamics models of entire Syn3A cells, which serves as an ultimate means of validation for cell states predicted by the WCM. 

The ultimate microscope, directed at a cell, would reveal the dynamics of all the cell’s components with atomic resolution. In contrast to their real-world counterparts, computational microscopes are currently on the brink of meeting this challenge. In this perspective, we show how an integrative approach can be employed to model an entire cell, the minimal cell, JCVI-syn3A, at full complexity. This step opens the way to interrogate the cell’s spatio-temporal evolution with molecular dynamics simulations, an approach that can be extended to other cell types in the near future. 

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.