Marco Cosentino Lagomarsino

Università degli Studi di Torino, Torino, Piedmont, Italy

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Publications (62)245.46 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: We monitored the dynamics of cell dimensions and reporter GFP expression in individual E. coli cells growing in a microfluidic chemostat using time-lapse fluorescence microscopy. This combination of techniques allows us to study the dynamical responses of single bacterial cells to nutritional shift-down or shift-up for longer times and with more precision over the chemical environment than similar experiments performed on conventional agar pads. We observed two E. coli strains containing different promoter-reporter gene constructs and measured how both their cell dimensions and the GFP expression change after nutritional upshift and downshift. As expected, both strains have similar adaptation dynamics for cell size rearrangement. However, the strain with a ribosomal RNA promoter dependent reporter has a faster GFP production rate than the strain with a constitutive promoter reporter. As a result, the mean GFP concentration in the former strain changes rapidly with the nutritional shift, while that in the latter strain remains relatively stable. These findings characterize the present microfluidic chemostat as a versatile platform for measuring single-cell bacterial dynamics and physiological transitions.
    The Analyst 08/2014; · 4.23 Impact Factor
  • Vittore F. Scolari, Marco Cosentino Lagomarsino
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    ABSTRACT: Recent experimental results suggest that the E. coli chromosome feels a self-attracting interaction of osmotic origin, and is condensed in foci by bridging interactions. Motivated by these findings, we explore a generic modeling framework combining solely these two ingredients, in order to characterize their joint effects. Specifically, we study a simple polymer physics computational model with weak ubiquitous short-ranged self attraction and stronger sparse bridging interactions. Combining theoretical arguments and simulations, we study the general phenomenology of polymer collapse induced by these dual contributions, in the case of regularly-spaced bridging. Our results distinguish a regime of classical Flory-like coil-globule collapse dictated by the interplay of excluded volume and attractive energy and a switch-like collapse where bridging interaction compete with entropy loss terms from the looped arms of a star-like rosette. Additionally, we show that bridging can induce stable compartmentalized domains. In these configurations, different "cores" of bridging proteins are kept separated by star-like polymer loops in an entropically favorable multi-domain configuration, with a mechanism that parallels micellar polysoaps. Such compartmentalized domains are stable, and do not need any intra-specific interactions driving their segregation. Domains can be stable also in presence of uniform attraction, as long as the uniform collapse is above its theta point.
    08/2014;
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    Jacopo Grilli, Mariacristina Romano, Federico Bassetti, Marco Cosentino Lagomarsino
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    ABSTRACT: Prokaryotes vary their protein repertoire mainly through horizontal transfer and gene loss. To elucidate the links between these processes and the cross-species gene-family statistics, we perform a large-scale data analysis of the cross-species variability of gene-family abundance (the number of members of the family found on a given genome). We find that abundance fluctuations are related to the rate of horizontal transfers. This is rationalized by a minimal theoretical model, which predicts this link. The families that are not captured by the model show abundance profiles that are markedly peaked around a mean value, possibly because of specific abundance selection. Based on these results, we define an abundance variability index that captures a family's evolutionary behavior (and thus some of its relevant functional properties) purely based on its cross-species abundance fluctuations. Analysis and model, combined, show a quantitative link between cross-species family abundance statistics and horizontal transfer dynamics, which can be used to analyze genome 'flux'. Groups of families with different values of the abundance variability index correspond to genome sub-parts having different plasticity in terms of the level of horizontal exchange allowed by natural selection.
    Nucleic Acids Research 05/2014; · 8.81 Impact Factor
  • Matteo Osella, Eileen Nugent, Marco Cosentino Lagomarsino
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    ABSTRACT: The coordination of cell growth and division is a long-standing problem in biology. Focusing on Escherichia coli in steady growth, we quantify cell division control using a stochastic model, by inferring the division rate as a function of the observable parameters from large empirical datasets of dividing cells. We find that (i) cells have mechanisms to control their size, (ii) size control is effected by changes in the doubling time, rather than in the single-cell elongation rate, (iii) the division rate increases steeply with cell size for small cells, and saturates for larger cells. Importantly, (iv) the current size is not the only variable controlling cell division, but the time spent in the cell cycle appears to play a role, and (v) common tests of cell size control may fail when such concerted control is in place. Our analysis illustrates the mechanisms of cell division control in E. coli. The phenomenological framework presented is sufficiently general to be widely applicable and opens the way for rigorous tests of molecular cell-cycle models.
    Proceedings of the National Academy of Sciences 02/2014; · 9.81 Impact Factor
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    ABSTRACT: The physical nature of the bacterial chromosome has important implications for its function. Using high-resolution dynamic tracking, we observe the existence of rare but ubiquitous 'rapid movements' of chromosomal loci exhibiting near-ballistic dynamics. This suggests that these movements are either driven by an active machinery or part of stress-relaxation mechanisms. Comparison with a null physical model for subdiffusive chromosomal dynamics shows that rapid movements are excursions from a basal subdiffusive dynamics, likely due to driven and/or stress-relaxation motion. Additionally, rapid movements are in some cases coupled with known transitions of chromosomal segregation. They do not co-occur strictly with replication, their frequency varies with growth condition and chromosomal coordinate, and they show a preference for longitudinal motion. These findings support an emerging picture of the bacterial chromosome as off-equilibrium active matter and help developing a correct physical model of its in vivo dynamic structure.
    Nature Communications 01/2014; 5:3854. · 10.02 Impact Factor
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    ABSTRACT: Recent biophysical approaches have provided key insights into the enthalpic and entropic forces that compact the nucleoid in the cell. Our biophysical approach combines two complementary, non-invasive and label-free techniques: a precisely timed steerable optical trap and a high throughput microcapillary Coulter counter. We demonstrate the ability of the latter technique to probe the physical properties and size of many purified nucleoids, at the individual nucleoid level. The DNA-binding protein H-NS is central to the organization of the bacterial genome. Our results show that nucleoids purified from the Δhns strain in the stationary phase expand approximately five fold more than the form observed in WT bacteria. This compaction is consistent with the role played by H-NS in regulating the nucleoid structure and the significant organizational changes that occur as the cell adapts to the stationary phase. We also study the permeability to the flow of ions and find that in the experiment nucleoids behave as solid colloids.
    Integrative Biology 12/2013; · 4.32 Impact Factor
  • Marco Gherardi, Salvatore Mandrà, Bruno Bassetti, Marco Cosentino Lagomarsino
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    ABSTRACT: The development of a complex system depends on the self-coordinated action of a large number of agents, often determining unexpected global behavior. The case of software evolution has great practical importance: knowledge of what is to be considered atypical can guide developers in recognizing and reacting to abnormal behavior. Although the initial framework of a theory of software exists, the current theoretical achievements do not fully capture existing quantitative data or predict future trends. Here we show that two elementary laws describe the evolution of package sizes in a Linux-based operating system: first, relative changes in size follow a random walk with non-Gaussian jumps; second, each size change is bounded by a limit that is dependent on the starting size, an intriguing behavior that we call "soft bound." Our approach is based on data analysis and on a simple theoretical model, which is able to reproduce empirical details without relying on any adjustable parameter and generates definite predictions. The same analysis allows us to formulate and support the hypothesis that a similar mechanism is shaping the distribution of mammalian body sizes, via size-dependent constraints during cladogenesis. Whereas generally accepted approaches struggle to reproduce the large-mass shoulder displayed by the distribution of extant mammalian species, this is a natural consequence of the softly bounded nature of the process. Additionally, the hypothesis that this model is valid has the relevant implication that, contrary to a common assumption, mammalian masses are still evolving, albeit very slowly.
    Proceedings of the National Academy of Sciences 12/2013; · 9.81 Impact Factor
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    ABSTRACT: In bacteria, chromosomal architecture shows strong spatial and temporal organization, and regulates key cellular functions, such as transcription. Tracking the motion of chromosomal loci at short timescales provides information related to both the physical state of the nucleo-protein complex and its local environment, independent of large-scale motions related to genome segregation. Here we investigate the short-time (0.1-10 s) dynamics of fluorescently labelled chromosomal loci in Escherichia coli at different growth rates. At these timescales, we observe for the first time a dependence of the loci's apparent diffusion on both their subcellular localization and chromosomal coordinate, and we provide evidence that the properties of the chromosome are similar in the tested growth conditions. Our results indicate that either non-equilibrium fluctuations due to enzyme activity or the organization of the genome as a polymer-protein complex vary as a function of the distance from the origin of replication.
    Nature Communications 06/2013; 4:3003. · 10.02 Impact Factor
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    I. Llopis, I. Pagonabarraga, M. Cosentino Lagomarsino, C. P. Lowe
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    ABSTRACT: We examine the phenomenon of hydrodynamic-induced cooperativity for pairs of flagellated micro-organism swimmers, of which spermatozoa cells are an example. We consider semiflexible swimmers, where inextensible filaments are driven by an internal intrinsic force and torque-free mechanism (intrinsic swimmers). The velocity gain for swimming cooperatively, which depends on both the geometry and the driving, develops as a result of the near-field coupling of bending and hydrodynamic stresses. We identify the regimes where hydrodynamic cooperativity is advantageous and quantify the change in efficiency. When the filaments' axes are parallel, hydrodynamic interaction induces a directional instability that causes semiflexible swimmers that profit from swimming together to move apart from each other. Biologically, this implies that flagella need to select different synchronized collective states and to compensate for directional instabilities (e.g., by binding) in order to profit from swimming together. By analyzing the cooperative motion of pairs of externally actuated filaments, we assess the impact that stress distribution along the filaments has on their collective displacements.
    Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics 03/2013; 87(3).
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    Mina Zarei, Bianca Sclavi, Marco Cosentino Lagomarsino
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    ABSTRACT: The H-NS chromosome-organizing protein in E. coli can stabilize genomic DNA loops, and form oligomeric structures connected to repression of gene expression. Motivated by the link between chromosome organization, protein binding and gene expression, we analyzed publicly available genomic data sets of various origins, from genome-wide protein binding profiles to evolutionary information, exploring the connections between chromosomal organization, gene-silencing, pseudo-gene localization and horizontal gene transfer. We report the existence of transcriptionally silent contiguous areas corresponding to large regions of H-NS protein binding along the genome, their position indicates a possible relationship with the known large-scale features of chromosome organization.
    Molecular BioSystems 03/2013; 9(4):758-67. · 3.35 Impact Factor
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    Marco Gherardi, Salvatore Mandrà, Bruno Bassetti, Marco Cosentino Lagomarsino
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    ABSTRACT: Open-source software is a complex system; its development depends on the self-coordinated action of a large number of agents. This study follows the size of the building blocks, called "packages", of the Ubuntu Linux operating system over its entire history. The analysis reveals a multiplicative diffusion process, constrained by size-dependent bounds, driving the dynamics of the package-size distribution. A formalization of this into a quantitative model is able to match the data without relying on any adjustable parameters, and generates definite predictions. Finally, we formulate the hypothesis that a similar non-stationary mechanism could be shaping the distribution of mammal body sizes.
    02/2013;
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    ABSTRACT: We generated a genome-wide replication profile in the genome of Lachancea kluyveri and assessed the relationship between replication and base composition. This species diverged from Saccharomyces cerevisiae before the ancestral whole genome duplication. The genome comprises 8 chromosomes among which a chromosomal arm of 1 Mb has a G+C-content much higher than the rest of the genome. We identified 252 active replication origins in L. kluyveri and found considerable divergence in origin location with S. cerevisiae and with L. waltii. Although some global features of S. cerevisiae replication are conserved: centromeres replicate early while telomeres replicate late, we found that replication origins both in L. kluyveri and L. waltii do not behave as evolutionary fragile sites. In L. kluyveri, replication timing along chromosomes alternates between regions of early and late activating origins, except for the 1 Mb GC-rich chromosomal arm. This chromosomal arm contains an origin consensus motif different from other chromosomes and is replicated early during S-phase. We showed that precocious replication results from the specific absence of late firing origins in this chromosomal arm. In addition, we found a correlation between GC-content and distance from replication origins as well as a lack of replication-associated compositional skew between leading and lagging strands specifically in this GC-rich chromosomal arm. These findings suggest that the unusual base composition in the genome of L. kluyveri could be linked to replication.
    Genome Biology and Evolution 01/2013; · 4.76 Impact Factor
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    ABSTRACT: We designed a microfluidic chemostat consisting of 600 sub-micron trapping/growth channels connected to two feeding channels. The microchemostat traps E. coli cells and forces them to grow in lines for over 50 generations. Excess cells, including the mother cells captured at the start of the process, are removed from both ends of the growth channels by the media flow. With the aid of time-lapse microscopy, we have monitored dynamic properties such as growth rate and GFP expression at the single-cell level for many generations while maintaining a population of bacteria of similar age. We also use the microchemostat to show how the population responds to dynamic changes in the environment. Since more than 100 individual bacterial cells are aligned and immobilized in a single field of view, the microchemostat is an ideal platform for high-throughput intracellular measurements. We demonstrate this capability by tracking with sub-diffraction resolution the movements of fluorescently tagged loci in more than one thousand cells on a single device. The device yields results comparable to conventional agar microscopy experiments with substantial increases in throughput and ease of analysis.
    Lab on a Chip 01/2013; · 5.70 Impact Factor
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    Matteo Osella, Marco Cosentino Lagomarsino
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    ABSTRACT: Gene networks exhibiting oscillatory dynamics are widespread in biology. The minimal regulatory designs giving rise to oscillations have been implemented synthetically and studied by mathematical modeling. However, most of the available analyses generally neglect the coupling of regulatory circuits with the cellular "chassis" in which the circuits are embedded. For example, the intracellular macromolecular composition of fast-growing bacteria changes with growth rate. As a consequence, important parameters of gene expression, such as ribosome concentration or cell volume, are growth-rate dependent, ultimately coupling the dynamics of genetic circuits with cell physiology. This work addresses the effects of growth rate on the dynamics of a paradigmatic example of genetic oscillator, the repressilator. Making use of empirical growth-rate dependencies of parameters in bacteria, we show that the repressilator dynamics can switch between oscillations and convergence to a fixed point depending on the cellular state of growth, and thus on the nutrients it is fed. The physical support of the circuit (type of plasmid or gene positions on the chromosome) also plays an important role in determining the oscillation stability and the growth-rate dependence of period and amplitude. This analysis has potential application in the field of synthetic biology, and suggests that the coupling between endogenous genetic oscillators and cell physiology can have substantial consequences for their functionality.
    Physical Review E 01/2013; 87(1-1):012726. · 2.31 Impact Factor
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    Nadia Jezequel, Marco Cosentino Lagomarsino, Francois Heslot, Philippe Thomen
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    ABSTRACT: Often, laboratory evolution experiments for large populations of microorganisms which cannot recombine show two distinct phases: an initial rapid increase in fitness followed by a slower regime. In order to explore the population structure and the evolutionary tree in the later stages of adaptation, we evolved a very large population of about 3×10(10) Acinetobacter baylyi bacteria for approximately 2800 generations from a single clone, while maintaining it in a chemostat at high dilution rate. Nitrate in limiting amount and as the sole nitrogen source was used as a selection pressure. Analysis via resequencing of genomes extracted from populations give proofs that diversity can establish in chemostat at long term in a very simple medium. To find out which biological parameters were targeted by adaptation, we measured the maximum growth rate, the nitrate uptake and the resistance to starvation. Overall, we find that maximum growth rate could be a reasonably good proxy for fitness. The late slow adaptation is compatible with selection coeffcients spanning a typical range of 10(-3) - 10(-2) per generation as estimated by resequencing, pointing to a possible subpopulations structuring.
    Genome Biology and Evolution 12/2012; · 4.76 Impact Factor
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    ABSTRACT: The adaptive evolution of large asexual populations is generally characterized by competition between clones carrying different beneficial mutations. This interference phenomenon slows down the adaptation speed and makes the theoretical description of the dynamics more complex with respect to the successional occurrence and fixation of beneficial mutations typical of small populations. A simplified modeling framework considering multiple beneficial mutations with equal and constant fitness advantage captures some of the essential features of the actual complex dynamics, and some key predictions from this model are verified in laboratory evolution experiments. However, in these experiments the relative advantage of a beneficial mutation is generally dependent on the genetic background. In particular, the general pattern is that, as mutations in different loci accumulate, the relative advantage of new mutations decreases, trend often referred to as "diminishing return" epistasis. In this paper, we propose a phenomenological model that generalizes the fixed-advantage framework to include in a simple way this feature. To evaluate the quantitative consequences of diminishing returns on the evolutionary dynamics, we approach the model analytically as well as with direct simulations. Finally, we show how the model parameters can be matched with data from evolutionary experiments in order to infer the mean effect of epistasis and derive order-of-magnitude estimates of the rate of beneficial mutations. Applying this procedure to two experimental data sets gives values of the beneficial mutation rate within the range of previous measurements.
    10/2012;
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    Nicolas Bruot, Jurij Kotar, Filippo de Lillo, Marco Cosentino Lagomarsino, Pietro Cicuta
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    ABSTRACT: Motile cilia are highly conserved structures in the evolution of organisms, generating the transport of fluid by periodic beating, through remarkably organized behavior in space and time. It is not known how these spatiotemporal patterns emerge and what sets their properties. Individual cilia are nonequilibrium systems with many degrees of freedom. However, their description can be represented by simpler effective force laws that drive oscillations, and paralleled with nonlinear phase oscillators studied in physics. Here a synthetic model of two phase oscillators, where colloidal particles are driven by optical traps, proves the role of the average force profile in establishing the type and strength of synchronization. We find that highly curved potentials are required for synchronization in the presence of noise. The applicability of this approach to biological data is also illustrated by successfully mapping the behavior of cilia in the alga Chlamydomonas onto the coarse-grained model.
    Physical Review Letters 10/2012; 109(16):164103. · 7.73 Impact Factor
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    Arianna Bottinelli, Bruno Bassetti, Marco Cosentino Lagomarsino, Marco Gherardi
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    ABSTRACT: Proteins participating in a protein-protein interaction network can be grouped into homology classes following their common ancestry. Proteins added to the network correspond to genes added to the classes, so the dynamics of the two objects are intrinsically linked. Here we first introduce a statistical model describing the joint growth of the network and the partitioning of nodes into classes, which is studied through a combined mean-field and simulation approach. We then employ this unified framework to address the specific issue of the age dependence of protein interactions through the definition of three different node wiring or divergence schemes. A comparison with empirical data indicates that an age-dependent divergence move is necessary in order to reproduce the basic topological observables together with the age correlation between interacting nodes visible in empirical data. We also discuss the possibility of nontrivial joint partition and topology observables.
    Physical Review E 10/2012; 86(4-1):041919. · 2.31 Impact Factor
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    ABSTRACT: Recent experimental and theoretical approaches have attempted to quantify the physical organization (compaction and geometry) of the bacterial chromosome with its complement of proteins (the nucleoid). The genomic DNA exists in a complex and dynamic protein-rich state, which is highly organized at various length scales. This has implications for modulating (when not directly enabling) the core biological processes of replication, transcription and segregation. We overview the progress in this area, driven in the last few years by new scientific ideas and new interdisciplinary experimental techniques, ranging from high space- and time-resolution microscopy to high-throughput genomics employing sequencing to map different aspects of the nucleoid-related interactome. The aim of this review is to present the wide spectrum of experimental and theoretical findings coherently, from a physics viewpoint. In particular, we highlight the role that statistical and soft condensed matter physics play in describing this system of fundamental biological importance, specifically reviewing classic and more modern tools from the theory of polymers. We also discuss some attempts toward unifying interpretations of the current results, pointing to possible directions for future investigation.
    Reports on Progress in Physics 07/2012; 75(7):076602. · 13.23 Impact Factor
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    Luigi Grassi, Jacopo Grilli, Marco Cosentino Lagomarsino
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    ABSTRACT: The widespread exchange of genes between bacteria must have consequences on the global architecture of their genomes, which are being found in the abundant genomic data available today. Most of the expansion of bacterial protein families can be attributed to transfer events, which are positively biased for smaller evolutionary distances between genomes, and more frequent for classes that are larger, when summed over all known bacteria. Moreover, "innovation" events where horizontal transfers carry exogenous evolutionary families appear to be less frequent for larger genomes. This dynamic expansion of evolutionary families is interconnected with the acquisition of new biological functions and thus with the size and distribution of the genes' functional categories found on a genome. This commentary presents our recent contributions to this line of work and possible future directions.
    Mobile genetic elements. 05/2012; 2(3):163-167.

Publication Stats

411 Citations
245.46 Total Impact Points

Institutions

  • 2010–2013
    • Università degli Studi di Torino
      Torino, Piedmont, Italy
    • University of Cambridge
      • Department of Physics: Cavendish Laboratory
      Cambridge, ENG, United Kingdom
    • Pierre and Marie Curie University - Paris 6
      • Génomique des microorganismes - UMR 7238
      Lutetia Parisorum, Île-de-France, France
  • 1999–2013
    • University of Milan
      • Department of Physics
      Milano, Lombardy, Italy
  • 2012
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
    • Università degli studi di Parma
      Parma, Emilia-Romagna, Italy
    • Sapienza University of Rome
      • Department of Physics
      Roma, Latium, Italy
    • Università degli Studi dell'Insubria
      Varese, Lombardy, Italy
  • 2005–2010
    • Institut Curie
      Lutetia Parisorum, Île-de-France, France
  • 2009
    • Imperial College London
      • Department of Physics
      London, ENG, United Kingdom
  • 2007–2009
    • University of Pavia
      • • Department of Physics
      • • Department of Mathematics "F. Casorati"
      Pavia, Lombardy, Italy
  • 2008
    • University of Barcelona
      • Departament de Física Fonamental
      Barcelona, Catalonia, Spain
  • 2003
    • FOM Institute AMOLF
      Amsterdamo, North Holland, Netherlands