Publications by authors named "Terence Hwa"

Unlabelled: The physiology and ecology of particle-associated marine bacteria are of growing interest, but our knowledge of their aggregation behavior and mechanisms controlling their association with particles remains limited. We have found that a particle-associated isolate, sp. ALT199 strain 4B03, and the related type-strain 27126 both form large (>500 μm) aggregates while growing in rich medium.

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Microbial ecosystems are commonly modeled by fixed interactions between species in steady exponential growth states. However, microbes often modify their environments so strongly that they are forced out of the exponential state into stressed or non-growing states. Such dynamics are typical of ecological succession in nature and serial-dilution cycles in the laboratory.

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Microbial ecosystems are commonly modeled by fixed interactions between species in steady exponential growth states. However, microbes often modify their environments so strongly that they are forced out of the exponential state into stressed or non-growing states. Such dynamics are typical of ecological succession in nature and serial-dilution cycles in the laboratory.

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Many biogeochemical functions involve bacteria utilizing solid substrates. However, little is known about the coordination of bacterial growth with the kinetics of attachment to and detachment from such substrates. In this quantitative study of Vibrio sp.

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Quantifying the contribution of individual molecular components to complex cellular processes is a grand challenge in systems biology. Here we establish a general theoretical framework (Functional Decomposition of Metabolism, FDM) to quantify the contribution of every metabolic reaction to metabolic functions, e.g.

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Metabolic cross-feeding plays vital roles in promoting ecological diversity. While some microbes depend on exchanges of essential nutrients for growth, the forces driving the extensive cross-feeding needed to support the coexistence of free-living microbes are poorly understood. Here we characterize bacterial physiology under self-acidification and establish that extensive excretion of key metabolites following growth arrest provides a collaborative, inter-species mechanism of stress resistance.

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While Vibrio splendidus is best known as an opportunistic pathogen in oysters, Vibrio splendidus strain 1A01 was first identified as an early colonizer of synthetic chitin particles incubated in seawater. To gain a better understanding of its metabolism, a genome-scale metabolic model (GSMM) of V. splendidus 1A01 was reconstructed.

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Bacterial fitness depends on adaptability to changing environments. In rich growth medium, which is replete with amino acids, Escherichia coli primarily expresses protein synthesis machineries, which comprise ~40% of cellular proteins and are required for rapid growth. Upon transition to minimal medium, which lacks amino acids, biosynthetic enzymes are synthesized, eventually reaching ~15% of cellular proteins when growth fully resumes.

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Protein concentrations are set by a complex interplay between gene-specific regulatory processes and systemic factors, including cell volume and shared gene expression machineries. Elucidating this interplay is crucial for discerning and designing gene regulatory systems. We quantitatively characterized gene-specific and systemic factors that affect transcription and translation genome-wide for across many conditions.

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Networks of molecular regulators are often the primary objects of focus in the study of gene regulation, with the machinery of protein synthesis tacitly relegated to the background. Shifting focus to the constraints imposed by the allocation of protein synthesis flux reveals surprising ways in which the actions of molecular regulators are shaped by physiological demands. Using carbon catabolite repression as a case study, we describe how physiological constraints are sensed through metabolic fluxes and how flux-controlled regulation gives rise to simple empirical relations between protein levels and the rate of cell growth.

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To swim and navigate, motile bacteria synthesize a complex motility machinery involving flagella, motors, and a sensory system. A myriad of studies has elucidated the molecular processes involved, but less is known about the coordination of motility expression with cellular physiology: In , motility genes are strongly up-regulated in nutrient-poor conditions compared to nutrient-replete conditions; yet a quantitative link to cellular motility has not been developed. Here, we systematically investigated gene expression, swimming behavior, cell growth, and available proteomics data across a broad spectrum of exponential growth conditions.

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Many cellular activities in bacteria are organized according to their growth rate. The notion that ppGpp measures the cell’s growth rate is well accepted in the field of bacterial physiology. However, despite decades of interrogation and the identification of multiple molecular interactions that connects ppGpp to some aspects of cell growth, we lack a system-level, quantitative picture of how this alleged “measurement” is performed.

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Sinking particulate organic carbon out of the surface ocean sequesters carbon on decadal to millennial timescales. Predicting the particulate carbon flux is therefore critical for understanding both global carbon cycling and the future climate. Microbes play a crucial role in particulate organic carbon degradation, but the impact of depth-dependent microbial dynamics on ocean-scale particulate carbon fluxes is poorly understood.

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To respond to fluctuating conditions, microbes typically need to synthesize novel proteins. As this synthesis relies on sufficient biosynthetic precursors, microbes must devise effective response strategies to manage depleting precursors. To better understand these strategies, we investigate the active response of Escherichia coli to changes in nutrient conditions, connecting transient gene expression to growth phenotypes.

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Bacterial cells navigate their environment by directing their movement along chemical gradients. This process, known as chemotaxis, can promote the rapid expansion of bacterial populations into previously unoccupied territories. However, despite numerous experimental and theoretical studies on this classical topic, chemotaxis-driven population expansion is not understood in quantitative terms.

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Much recent progress has been made to understand the impact of proteome allocation on bacterial growth; much less is known about the relationship between the abundances of the enzymes and their substrates, which jointly determine metabolic fluxes. Here, we report a correlation between the concentrations of enzymes and their substrates in Escherichia coli. We suggest this relationship to be a consequence of optimal resource allocation, subject to an overall constraint on the biomass density: For a cellular reaction network composed of effectively irreversible reactions, maximal reaction flux is achieved when the dry mass allocated to each substrate is equal to the dry mass of the unsaturated (or "free") enzymes waiting to consume it.

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Bacteria grown on a mixture of carbon substrates exhibit two utilization patterns: hierarchical utilization (HU) and simultaneous utilization (SU). How and why cells adopt these different behaviors remains poorly understood despite decades of research. Recent studies address various open questions from multiple viewpoints.

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Accurate measurements of cellular protein concentrations are invaluable to quantitative studies of gene expression and physiology in living cells. Here, we developed a versatile mass spectrometric workflow based on data-independent acquisition proteomics (DIA/SWATH) together with a novel protein inference algorithm (xTop). We used this workflow to accurately quantify absolute protein abundances in Escherichia coli for > 2,000 proteins over > 60 growth conditions, including nutrient limitations, non-metabolic stresses, and non-planktonic states.

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Microorganisms adjust metabolic activity to cope with diverse environments. While many studies have provided insights into how individual pathways are regulated, the mechanisms that give rise to coordinated metabolic responses are poorly understood. Here, we identify the regulatory mechanisms that coordinate catabolism and anabolism in Escherichia coli.

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The rate of cell growth is crucial for bacterial fitness and drives the allocation of bacterial resources, affecting, for example, the expression levels of proteins dedicated to metabolism and biosynthesis. It is unclear, however, what ultimately determines growth rates in different environmental conditions. Moreover, increasing evidence suggests that other objectives are also important, such as the rate of physiological adaptation to changing environments.

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Growth laws emerging from studies of cell populations provide essential constraints on the global mechanisms that coordinate cell growth. The foundation of bacterial cell cycle studies relies on two interconnected dogmas that were proposed more than 50 years ago-the Schaechter-Maaloe-Kjeldgaard growth law that relates cell mass to growth rate and Donachie's hypothesis of a growth-rate-independent initiation mass. These dogmas spurred many efforts to understand their molecular bases and physiological consequences.

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Many microorganisms exhibit nutrient preferences, exemplified by the 'hierarchical' consumption of certain carbon substrates. Here, we systematically investigate under which physiological conditions hierarchical substrate utilization occurs and its mechanisms of implementation. We show utilization hierarchy of Escherichia coli to be ordered by the carbon-uptake flux rather than the identity of the substrates.

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The ability of a species to colonize newly available habitats is crucial to its overall fitness. In general, motility and fast expansion are expected to be beneficial for colonization and hence for the fitness of an organism. Here we apply an evolution protocol to investigate phenotypical requirements for colonizing habitats of different sizes during range expansion by chemotaxing bacteria.

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Bacterial chemotaxis, the directed movement of cells along gradients of chemoattractants, is among the best-characterized subjects in molecular biology, but much less is known about its physiological roles. It is commonly seen as a starvation response when nutrients run out, or as an escape response from harmful situations. Here we identify an alternative role of chemotaxis by systematically examining the spatiotemporal dynamics of Escherichia coli in soft agar.

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