Scholars@Duke
Ophelia Shalini Venturelli

Ophelia Shalini Venturelli

Associate Professor in the Department of Biomedical Engineering
Biomedical Engineering

Selected Publications

Metabolic interplay drives population cycles in a cross-feeding microbial community.

Journal Article Nature communications · October 2025 Population cycles are prevalent in ecosystems and play key roles in determining their functions. While multiple mechanisms have been theoretically shown to generate population cycles, there are limited examples of mutualisms driving self-sustained oscillat ... Full text Cite

Decoding the role of the arginine dihydrolase pathway in shaping human gut community assembly and health-relevant metabolites.

Journal Article Cell systems · May 2025 The arginine dihydrolase pathway (arc operon) provides a metabolic niche by transforming arginine into metabolic byproducts. We investigate the role of the arc operon in probiotic Escherichia coli Nissle 1917 on human gut community assembly and health-rele ... Full text Cite

Phocaeicola vulgatus shapes the long-term growth dynamics and evolutionary adaptations of Clostridioides difficile.

Journal Article Cell host & microbe · January 2025 Clostridioides difficile can transiently or persistently colonize the human gut, posing a risk for infections. This colonization is influenced by complex molecular and ecological interactions with the human gut microbiota. By investigating C. difficile dyn ... Full text Cite

Microbial community interactions on a chip

Journal Article Proceedings of the National Academy of Sciences of the United States of America · September 24, 2024 Multispecies microbial communities drive most ecosystems on Earth. Chemical and biological interactions within these communities can affect the survival of individual members and the entire community. However, the prohibitively high number of possible inte ... Full text Cite

Elucidating human gut microbiota interactions that robustly inhibit diverse Clostridioides difficile strains across different nutrient landscapes.

Journal Article Nature communications · August 2024 The human gut pathogen Clostridioides difficile displays substantial inter-strain genetic variability and confronts a changeable nutrient landscape in the gut. We examined how human gut microbiota inter-species interactions influence the growth and toxin p ... Full text Cite

Microbial community-scale metabolic modelling predicts personalized short-chain fatty acid production profiles in the human gut.

Journal Article Nature microbiology · July 2024 Microbially derived short-chain fatty acids (SCFAs) in the human gut are tightly coupled to host metabolism, immune regulation and integrity of the intestinal epithelium. However, the production of SCFAs can vary widely between individuals consuming the sa ... Full text Cite

Dynamic Multiplexed Control and Modeling of Optogenetic Systems Using the High-Throughput Optogenetic Platform, Lustro.

Journal Article ACS synthetic biology · May 2024 The ability to control cellular processes using optogenetics is inducer-limited, with most optogenetic systems responding to blue light. To address this limitation, we leverage an integrated framework combining Lustro, a powerful high-throughput optogeneti ... Full text Cite

Massively parallel single-cell sequencing of diverse microbial populations.

Journal Article Nature methods · February 2024 Single-cell genetic heterogeneity is ubiquitous in microbial populations and an important aspect of microbial biology; however, we lack a broadly applicable and accessible method to study this heterogeneity in microbial populations. Here, we show a simple, ... Full text Cite

A Parametric Bayesian Optimization Framework for Batch Dynamical Systems

Conference Proceedings of the American Control Conference · January 1, 2024 We present a Bayesian Optimization (BO) framework for optimizing the performance of batch dynamical systems. A key distinctive aspect of this framework is that it uses a parametric machine learning model (a recurrent neural network - RNN) to learn the syst ... Full text Cite

Control points for design of taxonomic composition in synthetic human gut communities.

Journal Article Cell systems · December 2023 Microbial communities offer vast potential across numerous sectors but remain challenging to systematically control. We develop a two-stage approach to guide the taxonomic composition of synthetic microbiomes by precisely manipulating media components and ... Full text Cite

Integrating a tailored recurrent neural network with Bayesian experimental design to optimize microbial community functions.

Journal Article PLoS computational biology · September 2023 Microbiomes interact dynamically with their environment to perform exploitable functions such as production of valuable metabolites and degradation of toxic metabolites for a wide range of applications in human health, agriculture, and environmental cleanu ... Full text Cite

Single-cell analysis of multiple invertible promoters reveals differential inversion rates as a strong determinant of bacterial population heterogeneity.

Journal Article Science advances · August 2023 Population heterogeneity can promote bacterial fitness in response to unpredictable environmental conditions. A major mechanism of phenotypic variability in the human gut symbiont Bacteroides spp. involves the inversion of promoters that drive the e ... Full text Cite

Microbes as Communication & Decision-Making Networked Communities

Journal Article IEEE Nanotechnology Magazine · June 1, 2023 MICROBIAL COMMUNITIES EXHIbit complex behavior and play significant roles in many biological phenomena. Understanding the communication within and between bacterial species can illuminate the how, as well as the why of numerous interactions that enable the ... Full text Cite

Gut microbiota interspecies interactions shape the response of Clostridioides difficile to clinically relevant antibiotics.

Journal Article PLoS biology · May 2023 In the human gut, the growth of the pathogen Clostridioides difficile is impacted by a complex web of interspecies interactions with members of human gut microbiota. We investigate the contribution of interspecies interactions on the antibiotic response of ... Full text Cite

Programming bacteria for multiplexed DNA detection.

Journal Article Nature communications · April 2023 DNA is a universal and programmable signal of living organisms. Here we develop cell-based DNA sensors by engineering the naturally competent bacterium Bacillus subtilis (B. subtilis) to detect specific DNA sequences in the environment. The DNA sensor stra ... Full text Cite

Efficient plasmid transfer via natural competence in a microbial co-culture.

Journal Article Molecular systems biology · March 2023 The molecular and ecological factors shaping horizontal gene transfer (HGT) via natural transformation in microbial communities are largely unknown, which is critical for understanding the emergence of antibiotic-resistant pathogens. We investigate key fac ... Full text Cite

What is the key challenge in engineering microbiomes?

Journal Article Cell systems · February 2023 Full text Cite

Carbohydrate complexity limits microbial growth and reduces the sensitivity of human gut communities to perturbations.

Journal Article Nature ecology & evolution · January 2023 Dietary fibre impacts the growth dynamics of human gut microbiota, yet we lack a detailed and quantitative understanding of how these nutrients shape microbial interaction networks and responses to perturbations. By building human gut communities coupled w ... Full text Cite

Recurrent neural networks enable design of multifunctional synthetic human gut microbiome dynamics.

Journal Article eLife · June 2022 Predicting the dynamics and functions of microbiomes constructed from the bottom-up is a key challenge in exploiting them to our benefit. Current models based on ecological theory fail to capture complex community behaviors due to higher order interactions ... Full text Cite

Under-Oil Autonomously Regulated Oxygen Microenvironments: A Goldilocks Principle-Based Approach for Microscale Cell Culture.

Journal Article Advanced science (Weinheim, Baden-Wurttemberg, Germany) · April 2022 Oxygen levels in vivo are autonomously regulated by a supply-demand balance, which can be altered in disease states. However, the oxygen levels of in vitro cell culture systems, particularly microscale cell culture, are typically dominated by either supply ... Full text Cite

Polysaccharide utilization loci in Bacteroides determine population fitness and community-level interactions.

Journal Article Cell host & microbe · February 2022 Polysaccharide utilization loci (PULs) are co-regulated bacterial genes that sense nutrients and enable glycan digestion. Human gut microbiome members, notably Bacteroides, contain numerous PULs that enable glycan utilization and shape ecological dynamics. ... Full text Cite

Optimizing the Spatial Topology of Bacterial Relay Systems: Delay Minimization

Conference IEEE International Conference on Communications · January 1, 2022 Diffusion-based molecular communication (DBMC) between spatially separated bacterial colonies has limited range due to slow diffusive propagation. To this end, relay-aided DBMC with bacterial colonies as nodes is considered in this paper. A deterministic f ... Full text Cite

Negative interactions determine Clostridioides difficile growth in synthetic human gut communities.

Journal Article Molecular systems biology · October 2021 Understanding the principles of colonization resistance of the gut microbiome to the pathogen Clostridioides difficile will enable the design of defined bacterial therapeutics. We investigate the ecological principles of community resistance to C. difficil ... Full text Cite

Towards a deeper understanding of microbial communities: integrating experimental data with dynamic models.

Journal Article Current opinion in microbiology · August 2021 Microbial communities and their functions are shaped by complex networks of interactions among microbes and with their environment. While the critical roles microbial communities play in numerous environments have become increasingly appreciated, we have a ... Full text Cite

Integrating Systems and Synthetic Biology to Understand and Engineer Microbiomes.

Journal Article Annual review of biomedical engineering · July 2021 Microbiomes are complex and ubiquitous networks of microorganisms whose seemingly limitless chemical transformations could be harnessed to benefit agriculture, medicine, and biotechnology. The spatial and temporal changes in microbiome composition and func ... Full text Cite

Design of synthetic human gut microbiome assembly and butyrate production.

Journal Article Nature communications · May 2021 The capability to design microbiomes with predictable functions would enable new technologies for applications in health, agriculture, and bioprocessing. Towards this goal, we develop a model-guided approach to design synthetic human gut microbiomes for pr ... Full text Cite

Engineering Microbiomes-Looking Ahead.

Journal Article ACS synthetic biology · December 2020 Full text Cite

Investigating the dynamics of microbial consortia in spatially structured environments.

Journal Article Nature communications · May 2020 The spatial organization of microbial communities arises from a complex interplay of biotic and abiotic interactions, and is a major determinant of ecosystem functions. Here we design a microfluidic platform to investigate how the spatial arrangement of mi ... Full text Cite

Common principles and best practices for engineering microbiomes.

Journal Article Nature reviews. Microbiology · December 2019 Despite broad scientific interest in harnessing the power of Earth's microbiomes, knowledge gaps hinder their efficient use for addressing urgent societal and environmental challenges. We argue that structuring research and technology developments around a ... Full text Cite

Microbial Interaction Network Inference in Microfluidic Droplets.

Journal Article Cell systems · September 2019 Microbial interactions are major drivers of microbial community dynamics and functions but remain challenging to identify because of limitations in parallel culturing and absolute abundance quantification of community members across environments and replic ... Full text Cite

Scalable nonlinear programming framework for parameter estimation in dynamic biological system models.

Journal Article PLoS computational biology · March 2019 We present a nonlinear programming (NLP) framework for the scalable solution of parameter estimation problems that arise in dynamic modeling of biological systems. Such problems are computationally challenging because they often involve highly nonlinear an ... Full text Cite

Understanding and Engineering Distributed Biochemical Pathways in Microbial Communities.

Journal Article Biochemistry · January 2019 Microbiomes impact nearly every environment on Earth by modulating the molecular composition of the environment. Temporally changing environmental stimuli and spatial organization are major variables shaping the structure and function of microbiomes. The w ... Full text Cite

Deciphering microbial interactions in synthetic human gut microbiome communities.

Journal Article Molecular systems biology · June 2018 The ecological forces that govern the assembly and stability of the human gut microbiota remain unresolved. We developed a generalizable model-guided framework to predict higher-dimensional consortia from time-resolved measurements of lower-order assemblag ... Full text Cite

Programming mRNA decay to modulate synthetic circuit resource allocation.

Journal Article Nature communications · April 2017 Synthetic circuits embedded in host cells compete with cellular processes for limited intracellular resources. Here we show how funnelling of cellular resources, after global transcriptome degradation by the sequence-dependent endoribonuclease MazF, to a s ... Full text Cite

Towards Engineering Biological Systems in a Broader Context.

Journal Article Journal of molecular biology · February 2016 Significant advances have been made in synthetic biology to program information processing capabilities in cells. While these designs can function predictably in controlled laboratory environments, the reliability of these devices in complex, temporally ch ... Full text Cite

The Impact of Different Sources of Fluctuations on Mutual Information in Biochemical Networks.

Journal Article PLoS computational biology · October 2015 Stochastic fluctuations in signaling and gene expression limit the ability of cells to sense the state of their environment, transfer this information along cellular pathways, and respond to it with high precision. Mutual information is now often used to q ... Full text Cite

Population diversification in a yeast metabolic program promotes anticipation of environmental shifts.

Journal Article PLoS biology · January 2015 Delineating the strategies by which cells contend with combinatorial changing environments is crucial for understanding cellular regulatory organization. When presented with two carbon sources, microorganisms first consume the carbon substrate that support ... Full text Cite

Synergistic dual positive feedback loops established by molecular sequestration generate robust bimodal response.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · November 2012 Feedback loops are ubiquitous features of biological networks and can produce significant phenotypic heterogeneity, including a bimodal distribution of gene expression across an isogenic cell population. In this work, a combination of experiments and compu ... Full text Cite

The pro-longevity gene FoxO3 is a direct target of the p53 tumor suppressor.

Journal Article Oncogene · July 2011 FoxO transcription factors have a conserved role in longevity, and act as tissue-specific tumor suppressors in mammals. Several nodes of interaction have been identified between FoxO transcription factors and p53, a major tumor suppressor in humans and mic ... Full text Cite

Evolution favors protein mutational robustness in sufficiently large populations.

Journal Article BMC biology · July 2007 BackgroundAn important question is whether evolution favors properties such as mutational robustness or evolvability that do not directly benefit any individual but can influence the course of future evolution. Functionally similar proteins can di ... Full text Cite