Scholars@Duke
Lingchong You

Lingchong You

Professor of Biomedical Engineering
Biomedical Engineering
Box 90281, Durham, NC 27708-0281
1381 CIEMAS, 101 Science Drive, Durham, NC 27708

Selected Publications

Private benefit of β-lactamase dictates selection dynamics of combination antibiotic treatment.

Journal Article Nat Commun · September 27, 2024 β-lactam antibiotics have been prescribed for most bacterial infections since their discovery. However, resistance to β-lactams, mediated by β-lactamase (Bla) enzymes such as extended spectrum β-lactamases (ESBLs), has become widespread. Bla inhibitors can ... Full text Link to item Cite

Biomolecular condensates regulate cellular electrochemical equilibria.

Journal Article Cell · September 2024 Control of the electrochemical environment in living cells is typically attributed to ion channels. Here, we show that the formation of biomolecular condensates can modulate the electrochemical environment in bacterial cells, which affects cellular process ... Full text Cite

A 'rich-get-richer' mechanism drives patchy dynamics and resistance evolution in antibiotic-treated bacteria.

Journal Article Molecular systems biology · August 2024 Bacteria in nature often form surface-attached communities that initially comprise distinct subpopulations, or patches. For pathogens, these patches can form at infection sites, persist during antibiotic treatment, and develop into mature biofilms. Evidenc ... Full text Cite

Data-driven learning of structure augments quantitative prediction of biological responses.

Journal Article PLoS computational biology · June 2024 Multi-factor screenings are commonly used in diverse applications in medicine and bioengineering, including optimizing combination drug treatments and microbiome engineering. Despite the advances in high-throughput technologies, large-scale experiments typ ... Full text Cite

The collapse of cooperation during range expansion of Pseudomonas aeruginosa.

Journal Article Nature microbiology · May 2024 Cooperation is commonly believed to be favourable in spatially structured environments, as these systems promote genetic relatedness that reduces the likelihood of exploitation by cheaters. Here we show that a Pseudomonas aeruginosa population that exhibit ... Full text Cite

Phase transition of GvpU regulates gas vesicle clustering in bacteria.

Journal Article Nature microbiology · April 2024 Gas vesicles (GVs) are microbial protein organelles that support cellular buoyancy. GV engineering has multiple applications, including reporter gene imaging, acoustic control and payload delivery. GVs often cluster into a honeycomb pattern to minimize occ ... Full text Cite

Programming Dynamic Division of Labor Using Horizontal Gene Transfer.

Journal Article ACS synthetic biology · April 2024 The metabolic engineering of microbes has broad applications, including biomanufacturing, bioprocessing, and environmental remediation. The introduction of a complex, multistep pathway often imposes a substantial metabolic burden on the host cell, restrain ... Full text Cite

A generic approach to infer community-level fitness of microbial genes.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · April 2024 The gene content in a metagenomic pool defines the function potential of a microbial community. Natural selection, operating on the level of genomes or genes, shapes the evolution of community functions by enriching some genes while depriving the others. D ... Full text Cite

Duplicated antibiotic resistance genes reveal ongoing selection and horizontal gene transfer in bacteria.

Journal Article Nature communications · February 2024 Horizontal gene transfer (HGT) and gene duplication are often considered as separate mechanisms driving the evolution of new functions. However, the mobile genetic elements (MGEs) implicated in HGT can copy themselves, so positive selection on MGEs could d ... Full text Cite

Autoencoder neural networks enable low dimensional structure analyses of microbial growth dynamics.

Journal Article Nature communications · December 2023 The ability to effectively represent microbiome dynamics is a crucial challenge in their quantitative analysis and engineering. By using autoencoder neural networks, we show that microbial growth dynamics can be compressed into low-dimensional representati ... Full text Cite

Promotion of plasmid maintenance by heterogeneous partitioning of microbial communities.

Journal Article Cell systems · October 2023 Transferable plasmids play a critical role in shaping the functions of microbial communities. Previous studies suggested multiple mechanisms underlying plasmid persistence and abundance. Here, we focus on the interplay between heterogeneous community parti ... Full text Cite

Mapping single-cell responses to population-level dynamics during antibiotic treatment

Journal Article Molecular Systems Biology · July 11, 2023 Treatment of sensitive bacteria with beta-lactam antibiotics often leads to two salient population-level features: a transient increase in total population biomass before a subsequent decline, and a linear correlation between growth and killing rates. Howe ... Full text Cite

Toward predictive engineering of gene circuits.

Journal Article Trends in biotechnology · June 2023 Many synthetic biology applications rely on programming living cells using gene circuits - the assembly and wiring of genetic elements to control cellular behaviors. Extensive progress has been made in constructing gene circuits with diverse functions and ... Full text Cite

Interface of biomolecular condensates modulates redox reactions.

Journal Article Chem · June 2023 Biomolecular condensates mediate diverse cellular processes. The density transition process of condensate formation results in selective partitioning of molecules, which define a distinct chemical environment within the condensates. However, the fundamenta ... Full text Cite

A change of phase.

Journal Article Nature chemical biology · April 2023 Full text Cite

Programmable synthetic biomolecular condensates for cellular control.

Journal Article Nature chemical biology · April 2023 The formation of biomolecular condensates mediated by a coupling of associative and segregative phase transitions plays a critical role in controlling diverse cellular functions in nature. This has inspired the use of phase transitions to design synthetic ... Full text Cite

Engineering living materials by synthetic biology.

Journal Article Biophysics reviews · March 2023 Natural biological materials are programmed by genetic information and able to self-organize, respond to environmental stimulus, and couple with inorganic matter. Inspired by the natural system and to mimic their complex and delicate fabrication process an ... Full text Cite

Vertical and horizontal gene transfer tradeoffs direct plasmid fitness.

Journal Article Molecular systems biology · February 2023 Plasmid fitness is directed by two orthogonal processes-vertical transfer through cell division and horizontal transfer through conjugation. When considered individually, improvements in either mode of transfer can promote how well a plasmid spreads and pe ... Full text Cite

Horizontal gene transfer enables programmable gene stability in synthetic microbiota.

Journal Article Nat Chem Biol · November 2022 The functions of many microbial communities exhibit remarkable stability despite fluctuations in the compositions of these communities. To date, a mechanistic understanding of this function-composition decoupling is lacking. Statistical mechanisms have bee ... Full text Link to item Cite

Bringing cells to the edge.

Journal Article eLife · November 2022 A network of open channels allows cells and molecular cargo to travel from the center to the periphery of lab-grown colonies of Pseudomonas aeruginosa, helping to eradicate competing species. ... Full text Cite

Distributed information encoding and decoding using self-organized spatial patterns.

Journal Article Patterns (New York, N.Y.) · October 2022 Dynamical systems often generate distinct outputs according to different initial conditions, and one can infer the corresponding input configuration given an output. This property captures the essence of information encoding and decoding. Here, we demonstr ... Full text Cite

Intelligent nanoscope for rapid nanomaterial identification and classification.

Journal Article Lab on a chip · August 2022 Machine learning image recognition and classification of particles and materials is a rapidly expanding field. However, nanomaterial identification and classification are dependent on the image resolution, the image field of view, and the processing time. ... Full text Cite

Double-stranded RNA drives SARS-CoV-2 nucleocapsid protein to undergo phase separation at specific temperatures.

Journal Article Nucleic acids research · August 2022 Nucleocapsid protein (N-protein) is required for multiple steps in betacoronaviruses replication. SARS-CoV-2-N-protein condenses with specific viral RNAs at particular temperatures making it a powerful model for deciphering RNA sequence specificity in cond ... Full text Cite

Engineering consortia by polymeric microbial swarmbots.

Journal Article Nature communications · July 2022 Synthetic microbial consortia represent a new frontier for synthetic biology given that they can solve more complex problems than monocultures. However, most attempts to co-cultivate these artificial communities fail because of the winner-takes-all in nutr ... Full text Cite

Advances and challenges in programming pattern formation using living cells.

Journal Article Current opinion in chemical biology · June 2022 Spatial patterning of cell populations is a ubiquitous phenomenon in nature. Patterns occur at various length and time scales and exhibit immense diversity. In addition to offering a deeper understanding of the emergence of patterns in nature, the ability ... Full text Cite

Intra- and interpopulation transposition of mobile genetic elements driven by antibiotic selection.

Journal Article Nature ecology & evolution · May 2022 The spread of genes encoding antibiotic resistance is often mediated by horizontal gene transfer (HGT). Many of these genes are associated with transposons, a type of mobile genetic element that can translocate between the chromosome and plasmids. It is wi ... Full text Cite

Modulation of microbial community dynamics by spatial partitioning.

Journal Article Nat Chem Biol · April 2022 Microbial communities inhabit spatial architectures that divide a global environment into isolated or semi-isolated local environments, which leads to the partitioning of a microbial community into a collection of local communities. Despite its ubiquity an ... Full text Open Access Link to item Cite

Programmable living assembly of materials by bacterial adhesion.

Journal Article Nature chemical biology · March 2022 The field of engineered living materials aims to construct functional materials with desirable properties of natural living systems. A recent study demonstrated the programmed self-assembly of bacterial populations by engineered adhesion. Here we use this ... Full text Cite

Editorial overview: All microbial systems go`.

Journal Article Current opinion in microbiology · February 2022 Full text Cite

Engineered microbial consortia: strategies and applications.

Journal Article Microbial cell factories · November 2021 Many applications of microbial synthetic biology, such as metabolic engineering and biocomputing, are increasing in design complexity. Implementing complex tasks in single populations can be a challenge because large genetic circuits can be burdensome and ... Full text Cite

Predicting plasmid persistence in microbial communities by coarse-grained modeling.

Journal Article BioEssays : news and reviews in molecular, cellular and developmental biology · September 2021 Plasmids are a major type of mobile genetic elements (MGEs) that mediate horizontal gene transfer. The stable maintenance of plasmids plays a critical role in the functions and survival for microbial populations. However, predicting and controlling plasmid ... Full text Cite

Design patterns for engineering genetic stability.

Journal Article Current opinion in biomedical engineering · September 2021 The past 20 years have witnessed enormous progress in synthetic biology in the development of engineered cells for diverse applications, including biomanufacturing, materials fabrication, and potential therapeutics and diagnostics. However, it still remain ... Full text Cite

Living fabrication of functional semi-interpenetrating polymeric materials.

Journal Article Nat Commun · June 8, 2021 Cell-mediated living fabrication has great promise for generating materials with versatile, programmable functions. Here, we demonstrate the engineering of living materials consisting of semi-interpenetrating polymer networks (sIPN). The fabrication proces ... Full text Link to item Cite

Collective colony growth is optimized by branching pattern formation in Pseudomonas aeruginosa.

Journal Article Molecular systems biology · April 2021 Branching pattern formation is common in many microbes. Extensive studies have focused on addressing how such patterns emerge from local cell-cell and cell-environment interactions. However, little is known about whether and to what extent these patterns p ... Full text Cite

Repulsive expansion dynamics in colony growth and gene expression.

Journal Article PLoS computational biology · March 2021 Spatial expansion of a population of cells can arise from growth of microorganisms, plant cells, and mammalian cells. It underlies normal or dysfunctional tissue development, and it can be exploited as the foundation for programming spatial patterns. This ... Full text Cite

Engineering Microbiomes-Looking Ahead.

Journal Article ACS synthetic biology · December 2020 Full text Cite

The persistence potential of transferable plasmids.

Journal Article Nature communications · November 2020 Conjugative plasmids can mediate the spread and maintenance of diverse traits and functions in microbial communities. This role depends on the plasmid's ability to persist in a population. However, for a community consisting of multiple populations transfe ... Full text Cite

Temporal encoding of bacterial identity and traits in growth dynamics.

Journal Article Proc Natl Acad Sci U S A · August 18, 2020 In biology, it is often critical to determine the identity of an organism and phenotypic traits of interest. Whole-genome sequencing can be useful for this but has limited power for trait prediction. However, we can take advantage of the inherent informati ... Full text Link to item Cite

Interindividual Variation in Dietary Carbohydrate Metabolism by Gut Bacteria Revealed with Droplet Microfluidic Culture.

Journal Article mSystems · June 30, 2020 Culture and screening of gut bacteria enable testing of microbial function and therapeutic potential. However, the diversity of human gut microbial communities (microbiota) impedes comprehensive experimental studies of individual bacterial taxa. Here, we c ... Full text Link to item Cite

Bacterial Aggregation Leads to Collective Elimination.

Journal Article Trends in microbiology · April 2020 Faster growing bacteria tend to be killed faster by antibiotics. In a complex environment exposed to antibiotics, however, the fate of a bacterial population depends on diverse factors. In a new study, Schlomann et al. describes how sublethal antibiotics c ... Full text Cite

Growth-stage-dependent regulation of conjugation

Journal Article AIChE Journal · March 1, 2020 Plasmid conjugation is a driving force behind the spread of antibiotic resistance genes. While problematic for medical purposes, conjugation can be used for delivery of target genes in microbial communities, for example, for bioremediation. Physiological s ... Full text Cite

Quantifying E2F1 protein dynamics in single cells.

Journal Article Quantitative biology (Beijing, China) · March 2020 BackgroundE2F1 protein, a major effector of the Rb/E2F pathway plays a central role in regulating cell-fate decisions involved in proliferation, apoptosis, and differentiation. Its expression is highly dynamic and tightly modulated through a combi ... Full text Cite

Environmental and genetic determinants of plasmid mobility in pathogenic Escherichia coli.

Journal Article Sci Adv · January 2020 Plasmids are key vehicles of horizontal gene transfer (HGT), mobilizing antibiotic resistance, virulence, and other traits among bacterial populations. The environmental and genetic forces that drive plasmid transfer are poorly understood, however, due to ... Full text Link to item Cite

Bacterial metabolic state more accurately predicts antibiotic lethality than growth rate.

Journal Article Nature microbiology · December 2019 Growth rate and metabolic state of bacteria have been separately shown to affect antibiotic efficacy1-3. However, the two are interrelated as bacterial growth inherently imposes a metabolic burden4; thus, determining individual contri ... Full text Cite

Universal antibiotic tolerance arising from antibiotic-triggered accumulation of pyocyanin in Pseudomonas aeruginosa.

Journal Article PLoS biology · December 2019 Pseudomonas aeruginosa is an opportunistic pathogen that often infects open wounds or patients with cystic fibrosis. Once established, P. aeruginosa infections are notoriously difficult to eradicate. This difficulty is in part due to the ability of P. aeru ... Full text Cite

Emerging strategies for engineering microbial communities.

Journal Article Biotechnology advances · November 2019 From biosynthesis to bioremediation, microbes have been engineered to address a variety of biotechnological applications. A promising direction in these endeavors is harnessing the power of designer microbial consortia that consist of multiple populations ... Full text Cite

Versatile biomanufacturing through stimulus-responsive cell-material feedback.

Journal Article Nature chemical biology · October 2019 Small-scale production of biologics has great potential for enhancing the accessibility of biomanufacturing. By exploiting cell-material feedback, we have designed a concise platform to achieve versatile production, analysis and purification of diverse pro ... Full text Cite

Polar-opposite fates.

Journal Article Nature chemical biology · September 2019 Full text Cite

Glycolytic reprogramming in cancer cells: PKM2 dimer predominance induced by pulsatile PFK-1 activity.

Journal Article Physical biology · September 2019 The glycolytic enzyme pyruvate kinase M2 (PKM2) exists in both catalytically inactive dimeric and active tetrameric forms. In cancer cells, PKM2 dimer predominance contributes to tumor growth by triggering glycolytic reprogramming. However, the mechanism t ... Full text Cite

Massive computational acceleration by using neural networks to emulate mechanism-based biological models.

Journal Article Nature communications · September 2019 For many biological applications, exploration of the massive parametric space of a mechanism-based model can impose a prohibitive computational demand. To overcome this limitation, we present a framework to improve computational efficiency by orders of mag ... Full text Cite

Prophage Hunter: an integrative hunting tool for active prophages.

Journal Article Nucleic acids research · July 2019 Identifying active prophages is critical for studying coevolution of phage and bacteria, investigating phage physiology and biochemistry, and engineering designer phages for diverse applications. We present Prophage Hunter, a tool aimed at hunting for acti ... Full text Cite

Engineered Ribonucleoprotein Granules Inhibit Translation in Protocells.

Journal Article Molecular cell · July 2019 Liquid granules rich in intrinsically disordered proteins and RNA play key roles in critical cellular functions such as RNA processing and translation. Many details of the mechanism via which this occurs remain to be elucidated. Motivated by the lacuna in ... Full text Cite

Synthetic Pattern Formation.

Journal Article Biochemistry · March 2019 A fundamental question in biology is how biological patterns emerge. Because of the presence of numerous confounding factors, it is tremendously challenging to elucidate the mechanisms underlying pattern formation solely on the basis of studies of natural ... Full text Cite

A unifying framework for interpreting and predicting mutualistic systems.

Journal Article Nature communications · January 2019 Coarse-grained rules are widely used in chemistry, physics and engineering. In biology, however, such rules are less common and under-appreciated. This gap can be attributed to the difficulty in establishing general rules to encompass the immense diversity ... Full text Open Access Cite

Applying ecological resistance and resilience to dissect bacterial antibiotic responses.

Journal Article Sci Adv · December 2018 An essential property of microbial communities is the ability to survive a disturbance. Survival can be achieved through resistance, the ability to absorb effects of a disturbance without a notable change, or resilience, the ability to recover after being ... Full text Link to item Cite

Author Correction: Division of labour between Myc and G1 cyclins in cell cycle commitment and pace control.

Journal Article Nature communications · November 2018 This Article contains errors in Supplementary Table 3, which are described in the Author Correction associated with this Article. The simulation results in the Article were based on the correct formula and thus the results are not affected by this correcti ... Full text Cite

Biosynthetic transition metal chalcogenide semiconductor nanoparticles: Progress in synthesis, property control and applications

Journal Article Current Opinion in Colloid and Interface Science · November 1, 2018 Transition metal (TM) chalcogenides are a group of semiconductor materials with applications that range from antibacterial particles to thin films in energy conversion devices. Significant progress in synthetic biology combined with the benefits of low ene ... Full text Cite

Synthetic Biology: Reports from CSHA 2016 and More.

Journal Article Biotechnology journal · May 2018 Full text Cite

Robust, linear correlations between growth rates and β-lactam-mediated lysis rates.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · April 2018 It is widely acknowledged that faster-growing bacteria are killed faster by β-lactam antibiotics. This notion serves as the foundation for the concept of bacterial persistence: dormant bacterial cells that do not grow are phenotypically tolerant against β- ... Full text Cite

Metabolic division of labor in microbial systems.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · March 2018 Metabolic pathways are often engineered in single microbial populations. However, the introduction of heterologous circuits into the host can create a substantial metabolic burden that limits the overall productivity of the system. This limitation could be ... Full text Cite

Bacterially driven cadmium sulfide precipitation on porous membranes: Toward platforms for photocatalytic applications.

Journal Article Biointerphases · February 2018 The emerging field of biofabrication capitalizes on nature's ability to create materials with a wide range of well-defined physical and electronic properties. Particularly, there is a current push to utilize programmed, self-organization of living cells fo ... Full text Cite

Cyclin D/CDK4/6 activity controls G1 length in mammalian cells.

Journal Article PloS one · January 2018 The length of the G1 phase in the cell cycle shows significant variability in different cell types and tissue types. To gain insights into the control of G1 length, we generated an E2F activity reporter that captures free E2F activity after dissociation fr ... Full text Cite

Quantitative and synthetic biology approaches to combat bacterial pathogens.

Journal Article Current opinion in biomedical engineering · December 2017 Antibiotic resistance is one of the biggest threats to public health. The rapid emergence of resistant bacterial pathogens endangers the efficacy of current antibiotics and has led to increasing mortality and economic burden. This crisis calls for more rap ... Full text Cite

Programmable assembly of pressure sensors using pattern-forming bacteria.

Journal Article Nat Biotechnol · November 2017 Biological systems can generate microstructured materials that combine organic and inorganic components and possess diverse physical and chemical properties. However, these natural processes in materials fabrication are not readily programmable. Here, we u ... Full text Link to item Cite

Persistence and reversal of plasmid-mediated antibiotic resistance.

Journal Article Nature communications · November 2017 In the absence of antibiotic-mediated selection, sensitive bacteria are expected to displace their resistant counterparts if resistance genes are costly. However, many resistance genes persist for long periods in the absence of antibiotics. Horizontal gene ... Full text Cite

Drug detoxification dynamics explain the postantibiotic effect.

Journal Article Molecular systems biology · October 2017 The postantibiotic effect (PAE) refers to the temporary suppression of bacterial growth following transient antibiotic treatment. This effect has been observed for decades for a wide variety of antibiotics and microbial species. However, despite empirical ... Full text Cite

Hacking DNA copy number for circuit engineering.

Journal Article Nature genetics · July 2017 DNA copy number represents an essential parameter in the dynamics of synthetic gene circuits but typically is not explicitly considered. A new study demonstrates how dynamic control of DNA copy number can serve as an effective strategy to program robust os ... Full text Cite

Expression level is a key determinant of E2F1-mediated cell fate.

Journal Article Cell Death Differ · April 2017 The Rb/E2F network has a critical role in regulating cell cycle progression and cell fate decisions. It is dysfunctional in virtually all human cancers, because of genetic lesions that cause overexpression of activators, inactivation of repressors, or both ... Full text Link to item Cite

Long-term growth data of Escherichia coli at a single-cell level.

Journal Article Scientific data · March 2017 Long-term, single-cell measurement of bacterial growth is extremely valuable information, particularly in the study of homeostatic aspects such as cell-size and growth rate control. Such measurement has recently become possible due to the development of mi ... Full text Cite

Hybrid (Organic/Inorganic) Electrodes from Bacterially Precipitated CdS for PEC/Storage Applications

Journal Article Journal of Physical Chemistry C · February 23, 2017 Hybrid organic-inorganic compounds are receiving increasing attention for photoelectrochemical (PEC) devices due to their high electron transport efficiency and facile synthesis. Biosynthesis is a potentially low-cost and eco-friendly method to precipitate ... Full text Cite

Dissecting the effects of antibiotics on horizontal gene transfer: Analysis suggests a critical role of selection dynamics.

Journal Article BioEssays : news and reviews in molecular, cellular and developmental biology · December 2016 Horizontal gene transfer (HGT) is a major mechanism responsible for the spread of antibiotic resistance. Conversely, it is often assumed that antibiotics promote HGT. Careful dissection of the literature, however, suggests a lack of conclusive evidence sup ... Full text Cite

Elements of biological oscillations in time and space.

Journal Article Nature structural & molecular biology · December 2016 Oscillations in time and space are ubiquitous in nature and play critical roles in dynamic cellular processes. Although the molecular mechanisms underlying the generation of the dynamics are diverse, several distinct regulatory elements have been recognize ... Full text Cite

Processing Oscillatory Signals by Incoherent Feedforward Loops.

Journal Article PLoS computational biology · September 2016 From the timing of amoeba development to the maintenance of stem cell pluripotency, many biological signaling pathways exhibit the ability to differentiate between pulsatile and sustained signals in the regulation of downstream gene expression. While the n ... Full text Cite

Collective Space-Sensing Coordinates Pattern Scaling in Engineered Bacteria.

Journal Article Cell · April 21, 2016 Scale invariance refers to the maintenance of a constant ratio of developing organ size to body size. Although common, its underlying mechanisms remain poorly understood. Here, we examined scaling in engineered Escherichia coli that can form self-organized ... Full text Link to item Cite

Addressing biological uncertainties in engineering gene circuits.

Journal Article Integrative biology : quantitative biosciences from nano to macro · April 2016 Synthetic biology has grown tremendously over the past fifteen years. It represents a new strategy to develop biological understanding and holds great promise for diverse practical applications. Engineering of a gene circuit typically involves computationa ... Full text Cite

Antibiotics as a selective driver for conjugation dynamics.

Journal Article Nature microbiology · April 2016 It is generally assumed that antibiotics can promote horizontal gene transfer. However, because of a variety of confounding factors that complicate the interpretation of previous studies, the mechanisms by which antibiotics modulate horizontal gene transfe ... Full text Cite

Coupling spatial segregation with synthetic circuits to control bacterial survival.

Journal Article Molecular systems biology · February 2016 Engineered bacteria have great potential for medical and environmental applications. Fulfilling this potential requires controllability over engineered behaviors and scalability of the engineered systems. Here, we present a platform technology, microbial s ... Full text Cite

Cadmium sulphide quantum dots with tunable electronic properties by bacterial precipitation.

Journal Article RSC advances · January 2016 We present a new method to fabricate semiconducting, transition metal nanoparticles (NPs) with tunable bandgap energies using engineered Escherichia coli. These bacteria overexpress the Treponema denticola cysteine desulfhydrase gene to facil ... Full text Cite

Dynamic control and quantification of bacterial population dynamics in droplets.

Journal Article Biomaterials · August 2015 Culturing and measuring bacterial population dynamics are critical to develop insights into gene regulation or bacterial physiology. Traditional methods, based on bulk culture to obtain such quantification, have the limitations of higher cost/volume of rea ... Full text Cite

A noisy linear map underlies oscillations in cell size and gene expression in bacteria.

Journal Article Nature · July 2015 During bacterial growth, a cell approximately doubles in size before division, after which it splits into two daughter cells. This process is subjected to the inherent perturbations of cellular noise and thus requires regulation for cell-size homeostasis. ... Full text Open Access Cite

A power-law dependence of bacterial invasion on mammalian host receptors.

Journal Article PLoS computational biology · April 2015 Pathogenic bacteria such as Listeria and Yersinia gain initial entry by binding to host target cells and stimulating their internalization. Bacterial uptake entails successive, increasingly strong associations between receptors on the surface of bacteria a ... Full text Cite

Bacterial temporal dynamics enable optimal design of antibiotic treatment.

Journal Article PLoS Comput Biol · April 2015 There is a critical need to better use existing antibiotics due to the urgent threat of antibiotic resistant bacteria coupled with the reduced effort in developing new antibiotics. β-lactam antibiotics represent one of the most commonly used classes of ant ... Full text Link to item Cite

Collective antibiotic tolerance: mechanisms, dynamics and intervention.

Journal Article Nature chemical biology · March 2015 Bacteria have developed resistance against every antibiotic at a rate that is alarming considering the timescale at which new antibiotics are developed. Thus, there is a critical need to use antibiotics more effectively, extend the shelf life of existing a ... Full text Cite

Emergent dynamics from quorum eavesdropping.

Journal Article Chemistry & biology · December 2014 Numerous bacterial species utilize quorum sensing to communicate, but crosstalk often complicates the dynamics of mixed populations. In this issue of Chemistry & Biology, Wu and colleagues take advantage of synthetic gene circuits to elucidate interactions ... Full text Cite

Construction, visualization, and analysis of biological network models in Dynetica

Journal Article Quantitative Biology · December 1, 2014 Mathematical modeling has become an increasingly important aspect of biological research. Computer simulations help to improve our understanding of complex systems by testing the validity of proposed mechanisms and generating experimentally testable hypoth ... Full text Cite

Synthetic biology looks good on paper.

Journal Article Cell · November 2014 Tremendous progress has been made in the design and implementation of synthetic gene circuits, but real-world applications of such circuits have been limited. Cell-free circuits embedded on paper developed by Pardee et al. promise to deliver specific and r ... Full text Cite

Division of labour between Myc and G1 cyclins in cell cycle commitment and pace control.

Journal Article Nature communications · September 2014 A body of evidence has shown that the control of E2F transcription factor activity is critical for determining cell cycle entry and cell proliferation. However, an understanding of the precise determinants of this control, including the role of other cell- ... Full text Cite

Stochastic sensitivity analysis and kernel inference via distributional data.

Journal Article Biophysical journal · September 2014 Cellular processes are noisy due to the stochastic nature of biochemical reactions. As such, it is impossible to predict the exact quantity of a molecule or other attributes at the single-cell level. However, the distribution of a molecule over a populatio ... Full text Cite

Phenotypic signatures arising from unbalanced bacterial growth.

Journal Article PLoS computational biology · August 2014 Fluctuations in the growth rate of a bacterial culture during unbalanced growth are generally considered undesirable in quantitative studies of bacterial physiology. Under well-controlled experimental conditions, however, these fluctuations are not random ... Full text Cite

Generic metric to quantify quorum sensing activation dynamics.

Journal Article ACS synthetic biology · April 2014 Quorum sensing (QS) enables bacteria to sense and respond to changes in their population density. It plays a critical role in controlling different biological functions, including bioluminescence and bacterial virulence. It has also been widely adapted to ... Full text Cite

Programmed Allee effect in bacteria causes a tradeoff between population spread and survival.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · February 2014 Dispersal is necessary for spread into new habitats, but it has also been shown to inhibit spread. Theoretical studies have suggested that the presence of a strong Allee effect may account for these counterintuitive observations. Experimental demonstration ... Full text Cite

Cell biology. Cells listen to their inner voice.

Journal Article Science (New York, N.Y.) · February 2014 Full text Cite

Linear population allocation by bistable switches in response to transient stimulation.

Journal Article PloS one · January 2014 Many cellular decision processes, including proliferation, differentiation, and phenotypic switching, are controlled by bistable signaling networks. In response to transient or intermediate input signals, these networks allocate a population fraction to ea ... Full text Cite

Engineered cell-cell communication and its applications.

Journal Article Advances in biochemical engineering/biotechnology · January 2014 Over the past several decades, biologists have become more appreciative of the fundamental role of intercellular communication in natural systems spanning prokaryotic biofilms to eukaryotic developmental systems and neurological networks. From an engineeri ... Full text Cite

Temporal control of self-organized pattern formation without morphogen gradients in bacteria.

Journal Article Mol Syst Biol · October 8, 2013 Diverse mechanisms have been proposed to explain biological pattern formation. Regardless of their specific molecular interactions, the majority of these mechanisms require morphogen gradients as the spatial cue, which are either predefined or generated as ... Full text Link to item Cite

FOXO transcription factors control E2F1 transcriptional specificity and apoptotic function.

Journal Article Cancer research · October 2013 The transcription factor E2F1 is a key regulator of proliferation and apoptosis but the molecular mechanisms that mediate these cell fate decisions remain unclear. Here, we identify FOXO transcription factors as E2F1 target genes that act in a feed-forward ... Full text Cite

Synthetic Microbial Consortia and their Applications

Journal Article · August 27, 2013 While synthetic biology has created a multitude of novel behaviors in single populations of cells, it is increasingly recognized that the engineering of microbial consortia, which consist of two or more populations, is required to generate more complex dyn ... Full text Cite

Predictive power of cell-to-cell variability

Journal Article Quantitative Biology · June 1, 2013 Much of our current knowledge of biology has been constructed based on population-average measurements. However, advances in single-cell analysis have demonstrated the omnipresent nature of cell-to-cell variability in any population. On one hand, tremendou ... Full text Cite

A programmable microenvironment for cellular studies via microfluidics-generated double emulsions.

Journal Article Biomaterials · June 2013 High throughput cellular studies require small sample volume to reduce costs and enhance sensitivity. Microfluidics-generated water-in-oil (W/O) single emulsion droplet systems, in particular, provide uniform, well defined and discrete microenvironment for ... Full text Cite

Programmed cell death in bacteria and implications for antibiotic therapy.

Journal Article Trends in microbiology · June 2013 It is now well appreciated that programmed cell death (PCD) plays critical roles in the life cycle of diverse bacterial species. It is an apparently paradoxical behavior as it does not benefit the cells undergoing PCD. However, growing evidence suggests th ... Full text Cite

Synthetic microbial consortia and their applications

Chapter · May 21, 2013 While synthetic biology has created a multitude of novel behaviors in single populations of cells, it is increasingly recognized that the engineering of microbial consortia, which consist of two or more populations, is required to generate more complex dyn ... Full text Cite

Optimality and robustness in quorum sensing (QS)-mediated regulation of a costly public good enzyme.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · November 2012 Bacteria secrete a variety of public good exoproducts into their environment. These exoproducts are typically produced under the control of quorum sensing (QS), a signaling mechanism by which bacteria sense and respond to changes in their density. QS seems ... Full text Cite

Engineering microbial systems to explore ecological and evolutionary dynamics.

Journal Article Current opinion in biotechnology · October 2012 A major goal of biological research is to provide a mechanistic understanding of diverse biological processes. To this end, synthetic biology offers a powerful approach, whereby biological questions can be addressed in a well-defined framework. By construc ... Full text Cite

A synthetic biology approach to understanding cellular information processing.

Journal Article ACS synthetic biology · September 2012 The survival of cells and organisms requires proper responses to environmental signals. These responses are governed by cellular networks, which serve to process diverse environmental cues. Biological networks often contain recurring network topologies cal ... Full text Cite

A different life?

Journal Article Current opinion in chemical biology · August 2012 Full text Cite

Modeling spatiotemporal dynamics of bacterial populations.

Journal Article Methods in molecular biology (Clifton, N.J.) · January 2012 Quantitative modeling of spatiotemporal dynamics of cells facilitates understanding and engineering of biological systems. Using a synthetic bacterial ecosystem as a workbench, we present the approach to mathematically simulate the spatiotemporal populatio ... Full text Cite

Programming stress-induced altruistic death in engineered bacteria.

Journal Article Molecular systems biology · January 2012 Programmed death is often associated with a bacterial stress response. This behavior appears paradoxical, as it offers no benefit to the individual. This paradox can be explained if the death is 'altruistic': the killing of some cells can benefit the survi ... Full text Open Access Cite

The inoculum effect and band-pass bacterial response to periodic antibiotic treatment.

Journal Article Mol Syst Biol · 2012 The inoculum effect (IE) refers to the decreasing efficacy of an antibiotic with increasing bacterial density. It represents a unique strategy of antibiotic tolerance and it can complicate design of effective antibiotic treatment of bacterial infections. T ... Full text Open Access Link to item Cite

Tension and robustness in multitasking cellular networks.

Journal Article PLoS computational biology · January 2012 Cellular networks multitask by exhibiting distinct, context-dependent dynamics. However, network states (parameters) that generate a particular dynamic are often sub-optimal for others, defining a source of "tension" between them. Though multitasking is pe ... Full text Cite

Quantitative analysis of the spatiotemporal dynamics of a synthetic predator-prey ecosystem.

Journal Article Methods in molecular biology (Clifton, N.J.) · January 2012 A major focus in synthetic biology is the rational design and implementation of gene circuits to control dynamics of individual cells and, increasingly, cellular populations. Population-level control is highlighted in recent studies which attempt to design ... Full text Cite

Bayesian learning from marginal data in bionetwork models.

Journal Article Statistical applications in genetics and molecular biology · October 2011 In studies of dynamic molecular networks in systems biology, experiments are increasingly exploiting technologies such as flow cytometry to generate data on marginal distributions of a few network nodes at snapshots in time. For example, levels of intracel ... Full text Cite

Computation of steady-state probability distributions in stochastic models of cellular networks.

Journal Article PLoS computational biology · October 2011 Cellular processes are "noisy". In each cell, concentrations of molecules are subject to random fluctuations due to the small numbers of these molecules and to environmental perturbations. While noise varies with time, it is often measured at steady state, ... Full text Cite

Network calisthenics: control of E2F dynamics in cell cycle entry.

Journal Article Cell cycle (Georgetown, Tex.) · September 2011 Stimulation of quiescent mammalian cells with mitogens induces an abrupt increase in E2F1-3 expression just prior to the onset of DNA synthesis, followed by a rapid decline as replication ceases. This temporal adaptation in E2F facilitates a transient patt ... Full text Cite

Programming microbial population dynamics by engineered cell-cell communication.

Journal Article Biotechnology journal · July 2011 A major aim of synthetic biology is to program novel cellular behavior using engineered gene circuits. Early endeavors focused on building simple circuits that fulfill simple functions, such as logic gates, bistable toggle switches, and oscillators. These ... Full text Cite

Proliferation behavior of E. coli in a three-dimensional in vitro tumor model.

Journal Article Integrative biology : quantitative biosciences from nano to macro · June 2011 Advances in genetic engineering of non-pathogenic Escherichia coli (E. coli) have made this organism an attractive candidate for gene delivery vehicle. However, proliferation and transport behaviors of E. coli in three-dimensional (3D) tumor environment ar ... Full text Cite

Using noisy gene expression mediated by engineered adenovirus to probe signaling dynamics in mammalian cells

Journal Article Methods in Enzymology · May 30, 2011 Perturbations from environmental, genetic, and pharmacological sources can generate heterogeneous biological responses, even in genetically identical cells. Although these differences have important consequences on cell physiology and survival, they are of ... Full text Cite

Origin of bistability underlying mammalian cell cycle entry.

Journal Article Molecular systems biology · April 2011 Precise control of cell proliferation is fundamental to tissue homeostasis and differentiation. Mammalian cells commit to proliferation at the restriction point (R-point). It has long been recognized that the R-point is tightly regulated by the Rb-E2F sign ... Full text Cite

Viral-mediated noisy gene expression reveals biphasic E2f1 response to MYC.

Journal Article Molecular cell · February 2011 Gene expression mediated by viral vectors is subject to cell-to-cell variability, which limits the accuracy of gene delivery. When coupled with single-cell measurements, however, such variability provides an efficient means to quantify signaling dynamics i ... Full text Cite

Synthetic biology: Division of logic labour.

Journal Article Nature · January 2011 Full text Cite

Using noisy gene expression mediated by engineered adenovirus to probe signaling dynamics in mammalian cells.

Journal Article Methods in enzymology · January 2011 Perturbations from environmental, genetic, and pharmacological sources can generate heterogeneous biological responses, even in genetically identical cells. Although these differences have important consequences on cell physiology and survival, they are of ... Full text Cite

Stochastic E2F activation and reconciliation of phenomenological cell-cycle models.

Journal Article PLoS biology · September 2010 The transition of the mammalian cell from quiescence to proliferation is a highly variable process. Over the last four decades, two lines of apparently contradictory, phenomenological models have been proposed to account for such temporal variability. Thes ... Full text Open Access Cite

Oscillations by minimal bacterial suicide circuits reveal hidden facets of host-circuit physiology.

Journal Article PloS one · July 2010 Synthetic biology seeks to enable programmed control of cellular behavior though engineered biological systems. These systems typically consist of synthetic circuits that function inside, and interact with, complex host cells possessing pre-existing metabo ... Full text Open Access Cite

Image segmentation and dynamic lineage analysis in single-cell fluorescence microscopy.

Journal Article Cytometry. Part A : the journal of the International Society for Analytical Cytology · January 2010 An increasingly common component of studies in synthetic and systems biology is analysis of dynamics of gene expression at the single-cell level, a context that is heavily dependent on the use of time-lapse movies. Extracting quantitative data on the singl ... Full text Cite

Spatiotemporal modulation of biodiversity in a synthetic chemical-mediated ecosystem.

Journal Article Nature chemical biology · December 2009 Biodiversity, or the relative abundance of species, measures the persistence of an ecosystem. To better understand its modulation, we analyzed the spatial and temporal dynamics of a synthetic, chemical-mediated ecosystem that consisted of two engineered Es ... Full text Cite

Emergent bistability by a growth-modulating positive feedback circuit.

Journal Article Nature chemical biology · November 2009 Synthetic gene circuits are often engineered by considering the host cell as an invariable 'chassis'. Circuit activation, however, may modulate host physiology, which in turn can substantially impact circuit behavior. We illustrate this point by a simple c ... Full text Cite

Engineering multicellular systems by cell-cell communication.

Journal Article Current opinion in biotechnology · August 2009 Synthetic biology encompasses the design of new biological parts and systems as well as the modulation of existing biological networks to generate novel functions. In recent years, increasing emphasis has been placed on the engineering of population-level ... Full text Cite

Decoding biological principles using gene circuits.

Journal Article Molecular bioSystems · July 2009 A major flavor of synthetic biology is the creation of artificial gene circuits to perform user-defined tasks. One aspect of this area is to realize ever-increasingly more complicated circuit behavior. Such efforts have led to the identification and evalua ... Full text Cite

Optimal tuning of bacterial sensing potential.

Journal Article Molecular systems biology · January 2009 Through production and sensing of small signal molecules, quorum sensing (QS) enables bacteria to detect changes in their density and regulate their functions accordingly. QS systems are tremendously diverse in terms of their specific sensory components, t ... Full text Cite

Spatiotemporal modulation of biodiversity in a synthetic predator-prey ecosystem

Journal Article AIChE Annual Meeting, Conference Proceedings · December 1, 2008 Cite

Signal discrimination by differential regulation of protein stability in quorum sensing.

Journal Article Journal of molecular biology · October 2008 Quorum sensing (QS) is a communication mechanism exploited by a large variety of bacteria to coordinate gene expression at the population level. In Gram-negative bacteria, QS occurs via synthesis and detection of small chemical signals, most of which belon ... Full text Cite

Engineering microbial consortia: a new frontier in synthetic biology.

Journal Article Trends in biotechnology · September 2008 Microbial consortia are ubiquitous in nature and are implicated in processes of great importance to humans, from environmental remediation and wastewater treatment to assistance in food digestion. Synthetic biologists are honing their ability to program th ... Full text Cite

Noise reduction by diffusional dissipation in a minimal quorum sensing motif.

Journal Article PLoS Comput Biol · August 29, 2008 Cellular interactions are subject to random fluctuations (noise) in quantities of interacting molecules. Noise presents a major challenge for the robust function of natural and engineered cellular networks. Past studies have analyzed how noise is regulated ... Full text Link to item Cite

A bistable Rb-E2F switch underlies the restriction point.

Journal Article Nature cell biology · April 2008 The restriction point (R-point) marks the critical event when a mammalian cell commits to proliferation and becomes independent of growth stimulation. It is fundamental for normal differentiation and tissue homeostasis, and seems to be dysregulated in virt ... Full text Cite

Sensing and integration of Erk and PI3K signals by Myc.

Journal Article PLoS computational biology · February 2008 The transcription factor Myc plays a central role in regulating cell-fate decisions, including proliferation, growth, and apoptosis. To maintain a normal cell physiology, it is critical that the control of Myc dynamics is precisely orchestrated. Recent stu ... Full text Cite

A synthetic Escherichia coli predator-prey ecosystem.

Journal Article Molecular systems biology · January 2008 We have constructed a synthetic ecosystem consisting of two Escherichia coli populations, which communicate bi-directionally through quorum sensing and regulate each other's gene expression and survival via engineered gene circuits. Our synthetic ecosystem ... Full text Cite

A whole more than the sum of its synthetic parts.

Journal Article ACS chemical biology · January 2008 Synthetic biology is the realization of systems with desired behavior using biological materials. A recent addition to the field is a bipartite consortium of the bacterium Escherichia coli in which each species harbors complementary gene circuits that actu ... Full text Cite

Noise-limited frequency signal transmission in gene circuits.

Journal Article Biophysical journal · December 2007 To maintain normal physiology, cells must properly process diverse signals arising from changes in temperature, pH, nutrient concentrations, and other factors. Many physiological processes are controlled by temporal aspects of oscillating signals; that is, ... Full text Cite

Engineering synthetic killer circuits in bacteria

Journal Article Proceedings - Design Automation Conference · August 2, 2007 I will discuss our efforts to engineer suicidal bacteria, by using cell-cell communication to regulate cell killing. Lessons learned from these studies may provide insights into precise programming of bacterial dynamics for diverse applications. Copyright ... Full text Cite

Biology by design: reduction and synthesis of cellular components and behaviour.

Journal Article Journal of the Royal Society, Interface · August 2007 Biological research is experiencing an increasing focus on the application of knowledge rather than on its generation. Thanks to the increased understanding of cellular systems and technological advances, biologists are more frequently asking not only 'how ... Full text Cite

A synthetic biology challenge: making cells compute.

Journal Article Molecular bioSystems · May 2007 Advances in biology and engineering have enabled the reprogramming of cells with well-defined functions, leading to the emergence of synthetic biology. Early successes in this nascent field suggest its potential to impact diverse areas. Here, we examine th ... Full text Cite

Engineering novel synthetic biological systems

Journal Article IET Synthetic Biology · 2007 Cite

Evolving sensitivity.

Journal Article ACS chemical biology · December 2006 Engineering gene circuits with novel functions holds promise for broad applications in biology, engineering, and medicine. Directed evolution complements rational design as an important strategy for optimizing gene circuits and circuit elements. ... Full text Cite

Evolutionary design on a budget: robustness and optimality of bacteriophage T7.

Journal Article Systems biology · March 2006 Exploring how biological systems have been 'designed' by evolution to achieve robust behaviours is now a subject of increasing research effort. Yet, it still remains unclear how environmental factors may contribute to this process. This issue is addressed ... Full text Cite

A synthetic E.Coli predator-prey system

Journal Article AIChE Annual Meeting, Conference Proceedings · December 1, 2005 As one of the best studied model systems, a 'predator-prey' ecosystem has greatly contributed to our understanding of dynamics of ecological interactions. Using cell-cell communication coupled with regulated cell killing, we have designed and experimentall ... Cite

Long-term monitoring of bacteria undergoing programmed population control in a microchemostat.

Journal Article Science (New York, N.Y.) · July 2005 Using an active approach to preventing biofilm formation, we implemented a microfluidic bioreactor that enables long-term culture and monitoring of extremely small populations of bacteria with single-cell resolution. We used this device to observe the dyna ... Full text Cite

Programmed population control by cell-cell communication and regulated killing.

Journal Article Nature · April 2004 De novo engineering of gene circuits inside cells is extremely difficult, and efforts to realize predictable and robust performance must deal with noise in gene expression and variation in phenotypes between cells. Here we demonstrate that by coupling gene ... Full text Cite

Toward computational systems biology.

Journal Article Cell biochemistry and biophysics · January 2004 The development and successful application of high-throughput technologies are transforming biological research. The large quantities of data being generated by these technologies have led to the emergence of systems biology, which emphasizes large-scale, ... Full text Cite

Modeling biological systems using Dynetica--a simulator of dynamic networks.

Journal Article Bioinformatics (Oxford, England) · February 2003 UnlabelledWe present Dynetica, a user-friendly simulator of dynamic networks for constructing, visualizing, and analyzing kinetic models of biological systems. In addition to generic reaction networks, Dynetica facilitates construction of models o ... Full text Cite

Stochastic vs. deterministic modeling of intracellular viral kinetics.

Journal Article Journal of theoretical biology · October 2002 Within its host cell, a complex coupling of transcription, translation, genome replication, assembly, and virus release processes determines the growth rate of a virus. Mathematical models that account for these processes can provide insights into the unde ... Full text Cite

Dependence of epistasis on environment and mutation severity as revealed by in silico mutagenesis of phage t7.

Journal Article Genetics · April 2002 Understanding how interactions among deleterious mutations affect fitness may shed light on a variety of fundamental biological phenomena, including the evolution of sex, the buffering of genetic variations, and the topography of fitness landscapes. It rem ... Full text Cite

Effects of Escherichia coli physiology on growth of phage T7 in vivo and in silico.

Journal Article Journal of bacteriology · April 2002 Phage development depends not only upon phage functions but also on the physiological state of the host, characterized by levels and activities of host cellular functions. We established Escherichia coli at different physiological states by continuous cult ... Full text Cite

Simulating the growth of viruses.

Journal Article Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · January 2001 To explore how the genome of an organism defines its growth, we have developed a computer simulation for the intracellular growth of phage T7 on its E. coli host. Our simulation, which incorporates 30 years of genetic, biochemical, physiological, and bioph ... Full text Cite

Patterns of regulation from mRNA and protein time series.

Journal Article Metabolic engineering · July 2000 The rapid advance of genome sequencing projects challenges biologists to assign physiological roles to thousands of unknown gene products. We suggest here that regulatory functions and protein-protein interactions involving specific products may be inferre ... Full text Cite

Computation, prediction, and experimental tests of fitness for bacteriophage T7 mutants with permuted genomes.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · May 2000 We created a simulation based on experimental data from bacteriophage T7 that computes the developmental cycle of the wild-type phage and also of mutants that have an altered genome order. We used the simulation to compute the fitness of more than 10(5) mu ... Full text Cite

Amplification and spread of viruses in a growing plaque.

Journal Article Journal of theoretical biology · October 1999 The two-dimensional propagation of viruses through a "lawn" of receptive hosts, commonly called plaque growth, reflects the dynamics of interactions between viruses and host cells. Here we treat the amplification of viruses during plaque growth as a reacti ... Full text Cite

Prediction, design, and characterization of alternate genetic element orders for bacteriophage T7.

Journal Article Abstracts Of Papers Of The American Chemical Society · March 1999 Cite

The conformational study of β-D-GlcA-(1,4) -L-Rha in solution by NMR and molecular dynamics simulations

Journal Article Chemical Physics · November 15, 1997 The conformation and the dynamics of a disaccharide, β-D-GlcA-(1,4)-L-Rha (GR) in aqueous solution are studied using nuclear magnetic resonance (NMR) and unrestrained molecular dynamics (MD). NMR experiments reveal that the solution conformation of GR is i ... Full text Cite