Diverse phage communities are maintained stably on a clonal bacterial host.

Bacteriophages are the most abundant and phylogenetically diverse biological entities on Earth, yet the ecological mechanisms that sustain this extraordinary diversity remain unclear. In this study, we discovered that phage diversity consistently outstripped the diversity of their bacterial hosts under simple experimental conditions. We assembled and passaged dozens of diverse phage communities on a single, nonevolving strain of until the phage communities reached equilibrium.

Annotation-free prediction of microbial dioxygen utilization.

Aerobes require dioxygen (O) to grow; anaerobes do not. However, nearly all microbes-aerobes, anaerobes, and facultative organisms alike-express enzymes whose substrates include O, if only for detoxification. This presents a challenge when trying to assess which organisms are aerobic from genomic data alone.

Primitive purine biosynthesis connects ancient geochemistry to modern metabolism.

An unresolved question in the origin and evolution of life is whether a continuous path from geochemical precursors to the majority of molecules in the biosphere can be reconstructed from modern-day biochemistry. Here we identified a feasible path by simulating the evolution of biosphere-scale metabolism, using only known biochemical reactions and models of primitive coenzymes. We find that purine synthesis constitutes a bottleneck for metabolic expansion, which can be alleviated by non-autocatalytic phosphoryl coupling agents.

Protein cost minimization promotes the emergence of coenzyme redundancy.

SignificanceMetabolism relies on a small class of molecules (coenzymes) that serve as universal donors and acceptors of key chemical groups and electrons. Although metabolic networks crucially depend on structurally redundant coenzymes [e.g.

Top-down and bottom-up cohesiveness in microbial community coalescence.

Microbial communities frequently invade one another as a whole, a phenomenon known as community coalescence. Despite its potential importance for the assembly, dynamics, and stability of microbial consortia, as well as its prospective utility for microbiome engineering, our understanding of the processes that govern it is still very limited. Theory has suggested that microbial communities may exhibit cohesiveness in the face of invasions emerging from collective metabolic interactions across microbes and their environment.

Functional attractors in microbial community assembly.

For microbiome biology to become a more predictive science, we must identify which descriptive features of microbial communities are reproducible and predictable, which are not, and why. We address this question by experimentally studying parallelism and convergence in microbial community assembly in replicate glucose-limited habitats. Here, we show that the previously observed family-level convergence in these habitats reflects a reproducible metabolic organization, where the ratio of the dominant metabolic groups can be explained from a simple resource-partitioning model.

A thermodynamic atlas of carbon redox chemical space.

Redox biochemistry plays a key role in the transduction of chemical energy in living systems. However, the compounds observed in metabolic redox reactions are a minuscule fraction of chemical space. It is not clear whether compounds that ended up being selected as metabolites display specific properties that distinguish them from nonbiological compounds.

Functional genomic landscape of cancer-intrinsic evasion of killing by T cells.

The genetic circuits that allow cancer cells to evade destruction by the host immune system remain poorly understood. Here, to identify a phenotypically robust core set of genes and pathways that enable cancer cells to evade killing mediated by cytotoxic T lymphocytes (CTLs), we performed genome-wide CRISPR screens across a panel of genetically diverse mouse cancer cell lines that were cultured in the presence of CTLs. We identify a core set of 182 genes across these mouse cancer models, the individual perturbation of which increases either the sensitivity or the resistance of cancer cells to CTL-mediated toxicity.

Environmental boundary conditions for the origin of life converge to an organo-sulfur metabolism.

It has been suggested that a deep memory of early life is hidden in the architecture of metabolic networks, whose reactions could have been catalyzed by small molecules or minerals before genetically encoded enzymes. A major challenge in unravelling these early steps is assessing the plausibility of a connected, thermodynamically consistent proto-metabolism under different geochemical conditions, which are still surrounded by high uncertainty. Here we combine network-based algorithms with physico-chemical constraints on chemical reaction networks to systematically show how different combinations of parameters (temperature, pH, redox potential and availability of molecular precursors) could have affected the evolution of a proto-metabolism.

Emergent simplicity in microbial community assembly.

A major unresolved question in microbiome research is whether the complex taxonomic architectures observed in surveys of natural communities can be explained and predicted by fundamental, quantitative principles. Bridging theory and experiment is hampered by the multiplicity of ecological processes that simultaneously affect community assembly in natural ecosystems. We addressed this challenge by monitoring the assembly of hundreds of soil- and plant-derived microbiomes in well-controlled minimal synthetic media.

Genome-Scale Architecture of Small Molecule Regulatory Networks and the Fundamental Trade-Off between Regulation and Enzymatic Activity.

Metabolic flux is in part regulated by endogenous small molecules that modulate the catalytic activity of an enzyme, e.g., allosteric inhibition.

Remnants of an Ancient Metabolism without Phosphate.

Phosphate is essential for all living systems, serving as a building block of genetic and metabolic machinery. However, it is unclear how phosphate could have assumed these central roles on primordial Earth, given its poor geochemical accessibility. We used systems biology approaches to explore the alternative hypothesis that a protometabolism could have emerged prior to the incorporation of phosphate.

Unsupervised Identification of Isotope-Labeled Peptides.

In vivo isotopic labeling coupled with high-resolution proteomics is used to investigate primary metabolism in techniques such as stable isotope probing (protein-SIP) and peptide-based metabolic flux analysis (PMFA). Isotopic enrichment of carbon substrates and intracellular metabolism determine the distribution of isotopes within amino acids. The resulting amino acid mass distributions (AMDs) are convoluted into peptide mass distributions (PMDs) during protein synthesis.

Metabolic flux analysis using ¹³C peptide label measurements.

¹³C metabolic flux analysis (MFA) has become the experimental method of choice to investigate the cellular metabolism of microbes, cell cultures and plant seeds. Conventional steady-state MFA utilizes isotopic labeling measurements of amino acids obtained from protein hydrolysates. To retain spatial information in conventional steady-state MFA, tissues or subcellular fractions must be dissected or biochemically purified.