Jonas Cremer is an Assistant Professor in Biology. He is interested in the physiology and growth of prokaryotes. Jonas studied physics and biophysics in Munich. He was a postdoctoral research at the University of California, San Diego. Before joining Stanford, he was an Assistant Professor at the University of Groningen. His current research considers various scales of prokaryotic life (from the coordination of fundamental processes within cells to the collective behavior of cells in specific ecological settings), with a focus on gut bacteria and the model organism Escherichia coli.

Academic Appointments

Honors & Awards

  • Research Fellowship, German National Academy of Sciences Leopoldina (2011)

Boards, Advisory Committees, Professional Organizations

  • Member, German Physical Society (2009 - Present)
  • Member, American Physical Society (2012 - Present)
  • Member, American Society for Microbiology (2016 - Present)

Professional Education

  • Master, Ludwig-Maximilians University, Physics and biophysics (2007)
  • PhD, Ludwig-Maximilians University, Physics (2011)

Current Research and Scholarly Interests

We are a highly interdisciplinary research team, joined in our desire to better understand microbial life. To elucidate how bacterial cells accumulate biomass and grow, we work with the model organism Escherichia coli. Our approaches tightly combine quantitative experimentation with mathematical modeling to consider the coordination of major physiological processes across scales; from metabolism and protein synthesis, via cell-size control, to swimming. We further focus on gut bacteria and their interactions with the human host. Our analyses include considerations of intestinal physiology and diet patterns on the host side, as well as metabolism, growth-physiology, and ecology on the bacterial side.

2023-24 Courses

Stanford Advisees

All Publications

  • Conditionally unutilized proteins and their profound effects on growth and adaptation across microbial species. Current opinion in microbiology Balakrishnan, R., Cremer, J. 2023; 75: 102366


    Protein synthesis is an important determinant of microbial growth and response that demands a high amount of metabolic and biosynthetic resources. Despite these costs, microbial species from different taxa and habitats massively synthesize proteins that are not utilized in the conditions they currently experience. Based on resource allocation models, recent studies have begun to reconcile the costs and benefits of these conditionally unutilized proteins (CUPs) in the context of varying environmental conditions. Such massive synthesis of CUPs is crucial to consider in different areas of modern microbiology, from the systematic investigation of cell physiology, via the prediction of evolution in laboratory and natural environments, to the rational design of strains in biotechnology applications.

    View details for DOI 10.1016/j.mib.2023.102366

    View details for PubMedID 37625262

  • An optimal regulation of fluxes dictates microbial growth in and out of steady-state. eLife Chure, G., Cremer, J. 2023; 12


    Effective coordination of cellular processes is critical to ensure the competitive growth of microbial organisms. Pivotal to this coordination is the appropriate partitioning of cellular resources between protein synthesis via translation and the metabolism needed to sustain it. Here, we extend a low-dimensional allocation model to describe the dynamic regulation of this resource partitioning. At the core of this regulation is the optimal coordination of metabolic and translational fluxes, mechanistically achieved via the perception of charged- and uncharged-tRNA turnover. An extensive comparison with 60 data sets from Escherichia coli establishes this regulatory mechanism's biological veracity and demonstrates that a remarkably wide range of growth phenomena in and out of steady state can be predicted with quantitative accuracy. This predictive power, achieved with only a few biological parameters, cements the preeminent importance of optimal flux regulation across conditions and establishes low-dimensional allocation models as an ideal physiological framework to interrogate the dynamics of growth, competition, and adaptation in complex and ever-changing environments.

    View details for DOI 10.7554/eLife.84878

    View details for PubMedID 36896805

  • Changing Flows Balance Nutrient Absorption and Bacterial Growth along the Gut. Physical review letters Codutti, A., Cremer, J., Alim, K. 2022; 129 (13): 138101


    Small intestine motility and its ensuing flow of luminal content impact both nutrient absorption and bacterial growth. To explore this interdependence we introduce a biophysical description of intestinal flow and absorption. Rooted in observations of mice we identify the average flow velocity as the key control of absorption efficiency and bacterial growth, independent of the exact contraction pattern. We uncover self-regulation of contraction and flow in response to nutrients and bacterial levels to promote efficient absorption while restraining detrimental bacterial overgrowth.

    View details for DOI 10.1103/PhysRevLett.129.138101

    View details for PubMedID 36206418

  • Coordination of gene expression with cell size enables Escherichia coli to efficiently maintain motility across conditions. Proceedings of the National Academy of Sciences of the United States of America Honda, T., Cremer, J., Mancini, L., Zhang, Z., Pilizota, T., Hwa, T. 2022; 119 (37): e2110342119


    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 Escherichia coli, 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. Our results suggest that cells up-regulate the expression of motility genes at slow growth to compensate for reduction in cell size, such that the number of flagella per cell is maintained across conditions. The observed four or five flagella per cell is the minimum number needed to keep the majority of cells motile. This simple regulatory objective allows E. coli cells to remain motile across a broad range of growth conditions, while keeping the biosynthetic and energetic demands to establish and drive the motility machinery at the minimum needed. Given the strong reduction in flagella synthesis resulting from cell size increases at fast growth, our findings also provide a different physiological perspective on bacterial cell size control: A larger cell size at fast growth is an efficient strategy to increase the allocation of cellular resources to the synthesis of those proteins required for biomass synthesis and growth, while maintaining processes such as motility that are only needed on a per-cell basis.

    View details for DOI 10.1073/pnas.2110342119

    View details for PubMedID 36067284

  • Suboptimal resource allocation in changing environments constrains response and growth in bacteria. Molecular systems biology Balakrishnan, R., de Silva, R. T., Hwa, T., Cremer, J. 1800; 17 (12): e10597


    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. By synthetically modifying gene expression during changing conditions, we show how the competition by genes for the limited protein synthesis capacity constrains cellular response. Despite this constraint cells substantially express genes that are not required, trapping them in states where precursor levels are low and the genes needed to replenish the precursors are outcompeted. Contrary to common modeling assumptions, our findings highlight that cells do not optimize growth under changing environments but rather exhibit hardwired response strategies that may have evolved to promote fitness in their native environment. The constraint and the suboptimality of the cellular response uncovered provide a conceptual framework relevant for many research applications, from the prediction of evolution to the improvement of gene circuits in biotechnology.

    View details for DOI 10.15252/msb.202110597

    View details for PubMedID 34928547

  • A traveling-wave solution for bacterial chemotaxis with growth. Proceedings of the National Academy of Sciences of the United States of America Narla, A. V., Cremer, J., Hwa, T. 2021; 118 (48)


    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. Building on recent experimental progress, we here present a detailed analytical study that provides a quantitative understanding of how chemotaxis and cell growth lead to rapid and stable expansion of bacterial populations. We provide analytical relations that accurately describe the dependence of the expansion speed and density profile of the expanding population on important molecular, cellular, and environmental parameters. In particular, expansion speeds can be boosted by orders of magnitude when the environmental availability of chemicals relative to the cellular limits of chemical sensing is high. Analytical understanding of such complex spatiotemporal dynamic processes is rare. Our analytical results and the methods employed to attain them provide a mathematical framework for investigations of the roles of taxis in diverse ecological contexts across broad parameter regimes.

    View details for DOI 10.1073/pnas.2105138118

    View details for PubMedID 34819366

  • Chemotaxis as a navigation strategy to boost range expansion NATURE Cremer, J., Honda, T., Tang, Y., Wong-Ng, J., Vergassola, M., Hwa, T. 2019; 575 (7784): 658-+


    Bacterial chemotaxis, the directed movement of cells along gradients of chemoattractants, is among the best-characterized subjects in molecular biology1-10, but much less is known about its physiological roles11. It is commonly seen as a starvation response when nutrients run out, or as an escape response from harmful situations12-16. Here we identify an alternative role of chemotaxis by systematically examining the spatiotemporal dynamics of Escherichia coli in soft agar12,17,18. Chemotaxis in nutrient-replete conditions promotes the expansion of bacterial populations into unoccupied territories well before nutrients run out in the current environment. Low levels of chemoattractants act as aroma-like cues in this process, establishing the direction and enhancing the speed of population movement along the self-generated attractant gradients. This process of navigated range expansion spreads faster and yields larger population gains than unguided expansion following the canonical Fisher-Kolmogorov dynamics19,20 and is therefore a general strategy to promote population growth in spatially extended, nutrient-replete environments.

    View details for DOI 10.1038/s41586-019-1733-y

    View details for Web of Science ID 000500036800058

    View details for PubMedID 31695195

    View details for PubMedCentralID PMC6883170

  • An evolutionarily stable strategy to colonize spatially extended habitats NATURE Liu, W., Cremer, J., Li, D., Hwa, T., Liu, C. 2019; 575 (7784): 664-+


    The ability of a species to colonize newly available habitats is crucial to its overall fitness1-3. In general, motility and fast expansion are expected to be beneficial for colonization and hence for the fitness of an organism4-7. Here we apply an evolution protocol to investigate phenotypical requirements for colonizing habitats of different sizes during range expansion by chemotaxing bacteria8. Contrary to the intuitive expectation that faster is better, we show that there is an optimal expansion speed for a given habitat size. Our analysis showed that this effect arises from interactions among pioneering cells at the front of the expanding population, and revealed a simple, evolutionarily stable strategy for colonizing a habitat of a specific size: to expand at a speed given by the product of the growth rate and the habitat size. These results illustrate stability-to-invasion as a powerful principle for the selection of phenotypes in complex ecological processes.

    View details for DOI 10.1038/s41586-019-1734-x

    View details for Web of Science ID 000500036800059

    View details for PubMedID 31695198

    View details for PubMedCentralID PMC6883132

  • Cooperation in Microbial Populations: Theory and Experimental Model Systems JOURNAL OF MOLECULAR BIOLOGY Cremer, J., Melbinger, A., Wienand, K., Henriquez, T., Jung, H., Frey, E. 2019; 431 (23): 4599–4644


    Cooperative behavior, the costly provision of benefits to others, is common across all domains of life. This review article discusses cooperative behavior in the microbial world, mediated by the exchange of extracellular products called public goods. We focus on model species for which the production of a public good and the related growth disadvantage for the producing cells are well described. To unveil the biological and ecological factors promoting the emergence and stability of cooperative traits we take an interdisciplinary perspective and review insights gained from both mathematical models and well-controlled experimental model systems. Ecologically, we include crucial aspects of the microbial life cycle into our analysis and particularly consider population structures where ensembles of local communities (subpopulations) continuously emerge, grow, and disappear again. Biologically, we explicitly consider the synthesis and regulation of public good production. The discussion of the theoretical approaches includes general evolutionary concepts, population dynamics, and evolutionary game theory. As a specific but generic biological example, we consider populations of Pseudomonas putida and its regulation and use of pyoverdines, iron scavenging molecules, as public goods. The review closes with an overview on cooperation in spatially extended systems and also provides a critical assessment of the insights gained from the experimental and theoretical studies discussed. Current challenges and important new research opportunities are discussed, including the biochemical regulation of public goods, more realistic ecological scenarios resembling native environments, cell-to-cell signaling, and multispecies communities.

    View details for DOI 10.1016/j.jmb.2019.09.023

    View details for Web of Science ID 000506721800007

    View details for PubMedID 31634468

  • Spatiotemporal establishment of dense bacterial colonies growing on hard agar ELIFE Warren, M. R., Sun, H., Yan, Y., Cremer, J., Li, B., Hwa, T. 2019; 8


    The physical interactions of growing bacterial cells with each other and with their surroundings significantly affect the structure and dynamics of biofilms. Here a 3D agent-based model is formulated to describe the establishment of simple bacterial colonies expanding by the physical force of their growth. With a single set of parameters, the model captures key dynamical features of colony growth by non-motile, non EPS-producing E. coli cells on hard agar. The model, supported by experiment on colony growth in different types and concentrations of nutrients, suggests that radial colony expansion is not limited by nutrients as commonly believed, but by mechanical forces. Nutrient penetration instead governs vertical colony growth, through thin layers of vertically oriented cells lifting up their ancestors from the bottom. Overall, the model provides a versatile platform to investigate the influences of metabolic and environmental factors on the growth and morphology of bacterial colonies.

    View details for DOI 10.7554/eLife.41093

    View details for Web of Science ID 000460929900001

    View details for PubMedID 30855227

    View details for PubMedCentralID PMC6411370

  • Bacterial growth, flow, and mixing shape human gut microbiota density and composition GUT MICROBES Arnoldini, M., Cremer, J., Hwa, T. 2018; 9 (6): 559–66


    The human gut microbiota is highly dynamic, and host physiology and diet exert major influences on its composition. In our recent study, we integrated new quantitative measurements on bacterial growth physiology with a reanalysis of published data on human physiology to build a comprehensive modeling framework. This can generate predictions of how changes in different host factors influence microbiota composition. For instance, hydrodynamic forces in the colon, along with colonic water absorption that manifests as transit time, exert a major impact on microbiota density and composition. This can be mechanistically explained by their effect on colonic pH which directly affects microbiota competition for food. In this addendum, we describe the underlying analysis in more detail. In particular, we discuss the mixing dynamics of luminal content by wall contractions and its implications for bacterial growth and density, as well as the broader implications of our insights for the field of gut microbiota research.

    View details for DOI 10.1080/19490976.2018.1448741

    View details for Web of Science ID 000456896600008

    View details for PubMedID 29533125

    View details for PubMedCentralID PMC6287699

  • Effect of water flow and chemical environment on microbiota growth and composition in the human colon PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Cremer, J., Arnoldini, M., Hwa, T. 2017; 114 (25): 6438–43


    The human gut harbors a dynamic microbial community whose composition bears great importance for the health of the host. Here, we investigate how colonic physiology impacts bacterial growth, which ultimately dictates microbiota composition. Combining measurements of bacterial physiology with analysis of published data on human physiology into a quantitative, comprehensive modeling framework, we show how water flow in the colon, in concert with other physiological factors, determine the abundances of the major bacterial phyla. Mechanistically, our model shows that local pH values in the lumen, which differentially affect the growth of different bacteria, drive changes in microbiota composition. It identifies key factors influencing the delicate regulation of colonic pH, including epithelial water absorption, nutrient inflow, and luminal buffering capacity, and generates testable predictions on their effects. Our findings show that a predictive and mechanistic understanding of microbial ecology in the gut is possible. Such predictive understanding is needed for the rational design of intervention strategies to actively control the microbiota.

    View details for DOI 10.1073/pnas.1619598114

    View details for Web of Science ID 000403687300021

    View details for PubMedID 28588144

    View details for PubMedCentralID PMC5488924

  • Effect of flow and peristaltic mixing on bacterial growth in a gut-like channel PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Cremer, J., Segota, I., Yang, C., Arnoldini, M., Sauls, J. T., Zhang, Z., Gutierrez, E., Groisman, A., Hwa, T. 2016; 113 (41): 11414–19


    The ecology of microbes in the gut has been shown to play important roles in the health of the host. To better understand microbial growth and population dynamics in the proximal colon, the primary region of bacterial growth in the gut, we built and applied a fluidic channel that we call the "minigut." This is a channel with an array of membrane valves along its length, which allows mimicking active contractions of the colonic wall. Repeated contraction is shown to be crucial in maintaining a steady-state bacterial population in the device despite strong flow along the channel that would otherwise cause bacterial washout. Depending on the flow rate and the frequency of contractions, the bacterial density profile exhibits varying spatial dependencies. For a synthetic cross-feeding community, the species abundance ratio is also strongly affected by mixing and flow along the length of the device. Complex mixing dynamics due to contractions is described well by an effective diffusion term. Bacterial dynamics is captured by a simple reaction-diffusion model without adjustable parameters. Our results suggest that flow and mixing play a major role in shaping the microbiota of the colon.

    View details for DOI 10.1073/pnas.1601306113

    View details for Web of Science ID 000384886900047

    View details for PubMedID 27681630

    View details for PubMedCentralID PMC5068270

  • The emergence of cooperation from a single mutant during microbial life cycles JOURNAL OF THE ROYAL SOCIETY INTERFACE Melbinger, A., Cremer, J., Frey, E. 2015; 12 (108): 20150171


    Cooperative behaviour is widespread in nature, even though cooperating individuals always run the risk of being exploited by free-riders. Population structure effectively promotes cooperation given that a threshold in the level of cooperation was already reached. However, the question how cooperation can emerge from a single mutant, which cannot rely on a benefit provided by other cooperators, is still puzzling. Here, we investigate this question for a well-defined but generic situation based on typical life cycles of microbial populations where individuals regularly form new colonies followed by growth phases. We analyse two evolutionary mechanisms favouring cooperative behaviour and study their strength depending on the inoculation size and the length of a life cycle. In particular, we find that population bottlenecks followed by exponential growth phases strongly increase the survival and fixation probabilities of a single cooperator in a free-riding population.

    View details for DOI 10.1098/rsif.2015.0171

    View details for Web of Science ID 000358824600024

    View details for PubMedID 26063816

    View details for PubMedCentralID PMC4528582

  • Mobility, fitness collection, and the breakdown of cooperation PHYSICAL REVIEW E Gelimson, A., Cremer, J., Frey, E. 2013; 87 (4): 042711


    The spatial arrangement of individuals is thought to overcome the dilemma of cooperation: When cooperators engage in clusters, they might share the benefit of cooperation while being more protected against noncooperating individuals, who benefit from cooperation but save the cost of cooperation. This is paradigmatically shown by the spatial prisoner's dilemma model. Here, we study this model in one and two spatial dimensions, but explicitly take into account that in biological setups, fitness collection and selection are separated processes occurring mostly on vastly different time scales. This separation is particularly important to understand the impact of mobility on the evolution of cooperation. We find that even small diffusive mobility strongly restricts cooperation since it enables noncooperative individuals to invade cooperative clusters. Thus, in most biological scenarios, where the mobility of competing individuals is an irrefutable fact, the spatial prisoner's dilemma alone cannot explain stable cooperation, but additional mechanisms are necessary for spatial structure to promote the evolution of cooperation. The breakdown of cooperation is analyzed in detail. We confirm the existence of a phase transition, here controlled by mobility and costs, which distinguishes between purely cooperative and noncooperative absorbing states. While in one dimension the model is in the class of the voter model, it belongs to the directed percolation universality class in two dimensions.

    View details for DOI 10.1103/PhysRevE.87.042711

    View details for Web of Science ID 000317596600011

    View details for PubMedID 23679453

  • Growth dynamics and the evolution of cooperation in microbial populations SCIENTIFIC REPORTS Cremer, J., Melbinger, A., Frey, E. 2012; 2: 281


    Microbes providing public goods are widespread in nature despite running the risk of being exploited by free-riders. However, the precise ecological factors supporting cooperation are still puzzling. Following recent experiments, we consider the role of population growth and the repetitive fragmentation of populations into new colonies mimicking simple microbial life-cycles. Individual-based modeling reveals that demographic fluctuations, which lead to a large variance in the composition of colonies, promote cooperation. Biased by population dynamics these fluctuations result in two qualitatively distinct regimes of robust cooperation under repetitive fragmentation into groups. First, if the level of cooperation exceeds a threshold, cooperators will take over the whole population. Second, cooperators can also emerge from a single mutant leading to a robust coexistence between cooperators and free-riders. We find frequency and size of population bottlenecks, and growth dynamics to be the major ecological factors determining the regimes and thereby the evolutionary pathway towards cooperation.

    View details for DOI 10.1038/srep00281

    View details for Web of Science ID 000300586700002

    View details for PubMedID 22355791

    View details for PubMedCentralID PMC3282947

  • Evolutionary and population dynamics: A coupled approach PHYSICAL REVIEW E Cremer, J., Melbinger, A., Frey, E. 2011; 84 (5): 051921


    We study the interplay of population growth and evolutionary dynamics using a stochastic model based on birth and death events. In contrast to the common assumption of an independent population size, evolution can be strongly affected by population dynamics in general. Especially for fast reproducing microbes which are subject to selection, both types of dynamics are often closely intertwined. We illustrate this by considering different growth scenarios. Depending on whether microbes die or stop to reproduce (dormancy), qualitatively different behaviors emerge. For cooperating bacteria, a permanent increase of costly cooperation can occur. Even if not permanent, cooperation can still increase transiently due to demographic fluctuations. We validate our analysis via stochastic simulations and analytic calculations. In particular, we derive a condition for an increase in the level of cooperation.

    View details for DOI 10.1103/PhysRevE.84.051921

    View details for Web of Science ID 000297469000017

    View details for PubMedID 22181458

  • Evolutionary Game Theory in Growing Populations PHYSICAL REVIEW LETTERS Melbinger, A., Cremer, J., Frey, E. 2010; 105 (17): 178101


    Existing theoretical models of evolution focus on the relative fitness advantages of different mutants in a population while the dynamic behavior of the population size is mostly left unconsidered. We present here a generic stochastic model which combines the growth dynamics of the population and its internal evolution. Our model thereby accounts for the fact that both evolutionary and growth dynamics are based on individual reproduction events and hence are highly coupled and stochastic in nature. We exemplify our approach by studying the dilemma of cooperation in growing populations and show that genuinely stochastic events can ease the dilemma by leading to a transient but robust increase in cooperation.

    View details for DOI 10.1103/PhysRevLett.105.178101

    View details for Web of Science ID 000283054700018

    View details for PubMedID 21231082

  • Entropy Production of Cyclic Population Dynamics PHYSICAL REVIEW LETTERS Andrae, B., Cremer, J., Reichenbach, T., Frey, E. 2010; 104 (21): 218102


    Entropy serves as a central observable in equilibrium thermodynamics. However, many biological and ecological systems operate far from thermal equilibrium. Here we show that entropy production can characterize the behavior of such nonequilibrium systems. To this end we calculate the entropy production for a population model that displays nonequilibrium behavior resulting from cyclic competition. At a critical point the dynamics exhibits a transition from large, limit-cycle-like oscillations to small, erratic oscillations. We show that the entropy production peaks very close to the critical point and tends to zero upon deviating from it. We further provide analytical methods for computing the entropy production which agree excellently with numerical simulations.

    View details for DOI 10.1103/PhysRevLett.104.218102

    View details for Web of Science ID 000278150100063

    View details for PubMedID 20867139

  • The edge of neutral evolution in social dilemmas NEW JOURNAL OF PHYSICS Cremer, J., Reichenbach, T., Frey, E. 2009; 11
  • Anomalous finite-size effects in the Battle of the Sexes EUROPEAN PHYSICAL JOURNAL B Cremer, J., Reichenbach, T., Frey, E. 2008; 63 (3): 373–80