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This weekly seminar aims at gathering researchers from different fields (physicists, chemists and biologists) and from different institutes in central Paris. The objective is to cover a broad interface between physics, chemistry and biology, including experimental, numerical and/or theoretical approaches. To describe life sciences all scales are needed, from single molecules, to cells, tissues, organs, organisms, and populations. The scope of our seminar encompasses embryonic development, genetic regulation, evolution, biomechanics and cell migration, immunology, microbiology, synthetic biology, etc.

The seminar usually takes place on Fridays, at 1pm.

It is jointly organized by António Carlos Costa, Raphaël Janneret (LPENS) and Philippe Marcq (PMMH, ESPCI).

21 May 2021, 1pm

Peter Swain (University of Edinburgh)

Using a push-pull system of repressors to match glucose transporters to extracellular glucose

A common cellular task is to match gene expression dynamically to a range of concentrations of a regulatory molecule. Studying glucose transport in budding yeast, we determine mechanistically how such matching occurs for seven hexose transporters. By combining time-lapse microscopy with mathematical modelling, we find that levels of transporters are history-dependent and are regulated by a push-pull system comprising two types of repressors. I will argue that matching is favoured by a rate-affinity trade-off and that the regulatory system allows yeast to import glucose rapidly enough to starve competitors.

7 May 2021, 4pm

Thierry Emonet (Yale University)

Information processing and decision making during chemical navigation

During chemical navigation organisms must detect molecules, process that information, and make decision (e.g. turn or not to turn), which affects the signal they will encounter next. I will report on recent experiments in our lab that examine different aspects of this process. In the first part of the talk, I will discuss experiments that quantified the strategy used by walking fruit flies to navigate complex odor plumes, when the location and timing of odor packets are uncertain. In the second part of the talk, I will use the simpler and better characterized E. coli chemotaxis system to quantify how information puts a bound on maximal navigational performance, and how efficient a bacterium is at using the information it gathers in order to navigate.

30 April 2021, 1pm

Renaud Poincloux (Institut de Pharmacologie et Biologie Structurale, Toulouse)

Nanoscale architecture and mechanics of macrophage podosomes

Podosomes are macrophage adhesion structures devoted to the proteolysis of the extracellular matrix that are constitutively formed by monocyte/macrophage-derived cells. We have shown that they are crucial for the capability of macrophages to perform macrophage protease-dependent mesenchymal migration in vivo. Therefore, podosomes are emerging as specific targets to limit the deleterious macrophage infiltration in tumors. Podosomes are composed of a core of F-actin surrounded by adhesion complexes. We have shown that podosomes are capable of applying protrusive forces onto the extracellular environment, thanks to the development of a method called Protrusion Force Microscopy, which consists in measuring by Atomic Force Microscopy the nanometer deformations produced by macrophage podosomes on a compliant formvar membrane. We estimated the protrusive force generated at podosomes and showed that it oscillates with a constant period and requires combined acto-myosin contraction and actin polymerization. We have demonstrated that talin, vinculin and paxillin sustain protrusion force generated at the podosome core, and related force generation to the molecular extension of talin within the podosome ring, indicating that the ring sustains mechanical tension. We are now investigating the organization and regulation of actin filaments in podosomes and the precise localization of actin cross-linkers. Next to the demonstration that the ring is a site of tension balancing protrusion at the core, we are now determining how actin filaments in the core are collectively organized to generate podosome protrusive forces. Using in situ cryo-electron tomography, we have recently unveiled how the nanoscale architecture of macrophage podosomes enables basal membrane protrusion. In particular, we could show that the sum of the actin polymerization forces at the membrane is not sufficient to explain podosome protrusive forces, but that it can be rather explained by the elastic energy that is accumulated inside podosome actin filaments.

9 April 2021, 4pm

Mikhail Tikhonov (Washington University in St. Louis)

A spin-glass model for the interplay of ecology, and evolution, and biochemistry

The spin glass is a paradigmatic example of a difficult optimization problem arising from simple pairwise interactions, and unsurprisingly recurs in many contexts. One such context is the study of evolution, where spin-glass-like models are extensively used to simulate the complex “fitness landscape” experienced by the organisms as they evolve and interact. I will describe a class of eco-evolutionary models focusing on the simplest case of the interaction between organisms and their environment, namely competition for limited resources. In this class of models, the glassy landscape acquires the meaning of specifying the (complex, idiosyncratic) biochemistry. Focusing on the ecosystem response to external perturbations, I will argue that the spin-glass intuition allows us to expect several parameter regimes with distinct behaviors. In particular, the intuitive regime (“what the community is doing depends on the species it contains”) is flanked by two regimes where ecosystem response is predictable: one where this predictability emerges in spite of biochemical details, and another where it arises because of them.

2 April 2021, 1pm

Pauline Durand-Smet (Laboratoire MSC)

Plant cells under confinement: impact of geometrical cues on the cytoskeleton organization

Specific cell and tissue form is essential to support many biological functions of living organisms. During development, the creation of different shapes fundamentally requires the integration of genetic, biochemical and physical inputs.

In plants, it is well established that the cytoskeletal microtubule network plays a key role in the morphogenesis of the plant cell wall by guiding the organisation of new cell wall material. The cell cytoskeleton is thus a major determinant of plant cell shape. What is less clear is how cell geometry in turn influences the cytoskeletal organization.

To explore the relative contribution of geometry to the final organization of actin and microtubule cytoskeletons in single plant cells, we developed an experimental approach combining confinement of plant cells into micro-niches of controlled geometry with imaging of the cytoskeleton. A model of self-organizing microtubules in 3D predicts that severing of microtubules is an important parameter controlling the anisotropy of the microtubules network. We experimentally confirmed the model predictions by analysis of the response to shape change in plant cells with altered microtubule severing dynamics. This work is a first step towards assessing quantitatively how cell geometry controls cytoskeletal organization in plants.

26 March 2021, 1pm

Annafrancesca Rigato (Institut Fresnel, Marseille)

Growth-associated constraints and mechanical instabilities during epidermal morphogenesis in Drosophila

Cells in growing tissues are continuously subjected to and exerting active and passive forces. In fact, growth rate variations or changes in the spatial orientation of growth produce stress. To release the produced stress, the balance between growth and cell division is fundamental. Here we investigate the consequences on cell morphology when this balance is not present. A perfect model system is Drosophila abdominal epidermis, a continuous cell layer formed of two cell types: larval epithelial cells (LECs), and adult epidermis precursors (histoblasts). Histoblasts are organized in nests surrounded by LECs. Interestingly, histoblasts grow without dividing throughout the whole larval life. At the same time, LECs grow at a faster rate than histoblasts. Such imbalance causes an amazing morphological change in histoblasts, with cell junctions changing from straight to deeply folded. Such transition is reminiscent of buckling instabilities. We hypothesize that growing LECs compress histoblasts, causing junctional buckling. Live imaging observations of larvae in which we genetically altered cell cycle or growth of either cell type support this idea. Hence, we show that altering the balance between cell growth and divisions leads to unexpected morphological and mechanical regimes.

19 March 2021, 1pm

Alexandre Kabla (Cambridge University)

Rheology of cells and tissues

Cell migration and cell mechanics play a crucial role in a number of key biological processes, such as embryo development or cancer metastasis. It is therefore important to characterise the material properties of cells and tissues and the way they mechanically interact with their environment.

In this talk, I will present recent work we did to address these questions at the single-cell and tissue level. In particular, experimental studies on the mechanical response of in-vitro epithelial monolayers show that the material exhibits a strong time-dependent response over a broad range of timescales. In this situation, it is challenging to capture the response of the system with a few parameters without losing some of the material’s characteristic features. I will show that rheological models based on fractional calculus are effective empirical tools to summarize such complex data and highlight similarities across a broad range of systems.

5 March 2021, 1pm

Sigolène Meilhac (Institut Imagine – Institut Pasteur)

Looping of a tube : an asymmetric process to establish the double blood circulation in the heart

Left-right partitioning of the heart underlies the double blood circulation : pulmonary circulation in the right heart, systemic circulation in the left heart. Asymmetric heart morphogenesis is initiated in the embryo, when the tubular primordium acquires a rightward helical shape during the process of heart looping. This shape change determines cardiac chamber alignment and thus heart partitioning. Impairment of the left-right patterning of mesoderm precursor cells leads to the severe heterotaxy syndrome, including complex cardiac malformations and failure to establish the double blood circulation. Whereas the molecular cascade breaking the symmetry has been well characterised, how asymmetric signalling is sensed by precursor cells to generate asymmetric organogenesis has remained largely unknown.

Heart looping had been previously analysed as a binary parameter (left/right) of the helix direction, taken as a readout of the symmetry-breaking event. However, this is too reductionist to describe a 3D shape. We have developed a novel framework to quantify and simulate the fine heart loop shape in the mouse, as a readout of asymmetric morphogenesis. This has led us to propose a model of heart looping centred on the buckling of the tube growing between fixed poles. We have re-analysed the role of the major left determinant Nodal in this context. We have traced the contribution of Nodal expressing cells to regions of the heart tube poles. By manipulating Nodal signalling in time and space, we show that it is not involved in the buckling, but that it biases it. Nodal is required transiently in heart precursors, to amplify and coordinate opposed asymmetries at the heart tube poles and thus generate a robust helical shape.

Ongoing work aims at further dissecting the dynamics of left-right patterning, beyond Nodal signaling. Thus, we provide novel insight into the mechanisms of asymmetric heart morphogenesis relevant to complex congenital heart defects.

12 February 2021, 1pm

Marco Polin (University of Warwick)

Dial-a-Plume: Localised Photo-Bio-Convection on Demand

Microorganismal motility is often characterised by complex responses to environmental physico-chemical stimuli. Although the biological basis of these responses is often not well understood, their exploitation already promises novel avenues to directly control the motion of living active matter at both the individual and collective level. Here we leverage the phototactic ability of the model microalga Chlamydomonas reinhardtii to precisely control the timing and position of localised cell photo-accumulation, leading to the controlled development of isolated bioconvective plumes. This novel form of photo-bio-convection allows a precise, fast and reconfigurable control of the spatio-temporal dynamics of the instability and the ensuing global recirculation, which can be activated and stopped in real time. A simple continuum model accounts for the phototactic response of the suspension and demonstrates how the spatio-temporal dynamics of the illumination field can be used as a simple external switch to produce efficient bio-mixing.

5 February 2021, 1pm

Venkatesh Murthy (Harvard University)

Sensing the chemical world and making sense of it

The olfactory system senses chemicals in the environment to guide behavior in animals. Fluctuating mixtures of chemicals, transported in fluid environments, are detected by an array of olfactory sensors and parsed by neural circuits to recognize odor objects, which then inform behavioral decisions. Some key questions for chemical sensing systems include how they can detect relevant molecules that are embedded in a sea of distractors, and how they use sparse intermittent stimuli to navigate. We work with theorists to frame these questions quantitatively and use experiments in mice to address them. I will present some examples from our recent and ongoing work.

29 January 2021, 1pm

Michael Rera (CRI)

Ageing: what the Smurf?

Ageing is a complex process, broadly affecting living organisms in extremely various ways, ranging from the negligible senescence of some trees and arthropods, through the sudden post-reproduction death of salmon and desert organisms, to our human ageing with what has long been described as a time dependent exponential increase of the mortality risk.

Drosophila melanogaster and Mus musculus, the fruit fly and mouse, are two broadly used model organisms for studying ageing mostly because they show an apparent exponential increase of their mortality risk, same as in humans. Using the first model system, about 10 years ago I identified a physiological marker preceding death – fruit flies would turn blue when fed a non-toxic food dye. This simple visual cue allows us to identify individuals at a different stage of their life amongst a cohort of individuals and study aging and progress towards death.

We use this tool to question our knowledge regarding ageing, showed the broad conservation of this end-of-life phenotype in different drosophila subspecies, nematodes, zebrafish and killifish as well as develop a novel mathematical model for ageing allowing the experimental quantification of various “ageing parameters”.

15 January 2021, 1pm

Claire Wyart (ICM)

Tasting from within in the vertebrate spinal cord? A novel sensory interface controlling development, posture and innate immunity

The cerebrospinal fluid (CSF) is a complex solution circulating around the brain and spinal cord. Multiple evidence indicate that the activity and the development of the nervous system can be influenced by the content and flow of the CSF. Yet, it is not known how neuronal activity changes as a function of the physico-chemical properties of the CSF.

We identify throughout vertebrate species, ciliated neurons at the interface between the CSF and the nervous system that are in ideal position to sense CSF cues, to relay information to local networks and to regulate CSF content by secretion.

By combining electrophysiology, optogenetics and calcium imaging in vivo in larval zebrafish, we demonstrate that neurons contacting the CSF detect local bending of the spinal cord and in turn feedback GABAergic inhibition to multiple interneurons driving locomotion and posture in the spinal cord and hindbrain. Such inhibitory feedback modulates neuronal target in a state-dependent manner, depending on the fact that the animal is at rest or actively moving at a define speed.

Behavioral analysis of animals deprived of this sensory pathway reveals differential effects on speed for slow and fast regimes, as well as impairments in the control of posture during active locomotion. Our work first sheds light on the cellular and network mechanisms enabling sensorimotor integration of mechanical and chemical cues from the CSF onto motor circuits controlling locomotion and posture in the spinal cord.

We will present converging evidence that this interoceptive sensory pathway is involved in guiding a straight body axis throughout life, as well as innate immunity via the detection and combat of pathogens intruding the CSF.

17 December 2020, 11am

Jonathan Fouchard (IBPS)

Curling and buckling of epithelial monolayers, some experimental insights

Epithelial monolayers are soft thin sheets which shape the body and organs of many multi-cellular organisms. Competition between stretching and bending characterizes shape transitions of thin elastic sheets. While stretching dominates the mechanical response in tension, bending dominates in compression after an abrupt buckling transition. As opposed to inert materials, the morphogenesis of epithelial monolayers is largely influenced by endogenous ATP-dependent forces, which generate in-plane tension and active torques due to the polarization of myosin II molecular motors.

Here, we address the dialog between in-plane and out-of-plane forces in vitro, in epithelial monolayers devoid of substrate and suspended between parallel plates.

I will show that curls of high curvature form spontaneously at the free edge of these monolayers, which we use to estimate the active torques and the bending modulus of the tissue. I will also show that these tissues buckle in response to compression in a time-dependent and myosin II-dependent manner.

3 December 2020, 11am

Ramiro Godoy-Diana (PMMH, ESPCI)

The burst-and-coast regime in fish swimming

Body and caudal fin undulations are a widespread locomotion strategy in fish, and their swimming kinematics is usually described by a characteristic frequency and amplitude of the tail-beat oscillation. In some cases, fish use intermittent gaits, where a single frequency is not enough to fully describe their kinematics. Energy efficiency arguments have been invoked in the literature to explain this so-called burst-and-coast regime but well controlled experimental data are scarce. I will discuss our recent results on an experiment with burst-and-coast swimmers and a numerical model based on the observations showing that the observed burst-and-coast regime can be understood as obeying a minimization of cost of transport.

Ref: Li et al. (2020) Burst-and-coast swimmers optimize gait by adapting unique intrinsic cycle arXiv:2002.09176

26 November 2020, 11am

António Carlos Costa (LPENS)

Physics of Behavior Across Scales

Behavior exhibits multiple spatio-temporal scales: from fast control of the body posture by neural activity, to the slower neuromodulation of exploratory strategies all the way to ageing. How can we bridge these scales? We leverage the interplay between microscopic variability and macroscopic order, fundamental to statistics physics, to extract predictive coarse-grained dynamics from data. We reconstruct the state space as a sequence of measurements, partition the resulting space as to maximize entropy, and choose the sequence length to maximize predictive information. We approximate the dynamics of densities in the partitioned state space through transfer operators, providing an accurate statistical model on multiple scales. The operator spectrum provides a principled means of timescale separation and coarse-graining. We illustrate our approach using high-resolution posture measurements of the nematode C. elegans, and show that long-time changes in exploratory strategies (10’s of minutes) can be extracted from fine scale posture samples (10’s of milliseconds).

19 November 2020, 11am

Efe Ilker (Institut Curie)

Disentangling the effect of metabolic costs in selection

Metabolism and evolution are closely connected: if a mutation incurs extra energetic costs for an organism, there is a baseline selective disadvantage that may or may not be compensated for by other adaptive effects. A long-standing, but to date unproven, hypothesis [1] is that this disadvantage is equal to the fractional cost relative to the total resting metabolic expenditure. I will present our recent work [2] which validates this hypothesis from physical principles through a general growth model and show that it holds to excellent approximation for experimental parameters drawn from a wide range of species. We will also overview the significance of this contribution from metabolic expenditures in the course of evolution, by considering the elements of population dynamics. As an example, I will demonstrate that a close inspection on the thermodynamic costs, noise suppression performance and selection shows intriguing aspects about the evolution of microRNA regulated gene networks which play a critical role by controlling developmental processes of complex organisms and related diseases.

[1] L. E. Orgel and F. H. Crick, Nature 284, 604 (1980)
[2] E. Ilker and M. Hinczewski, Phys. Rev. Lett. 122, 238101 (2019)

5 November 2020, 4pm

Paul François (McGill University)

Phenotypic models of immune response : from single cells to cytokine code

T cells have to make life-or-death immune decisions based on sensitive and specific interactions with self and/or foreign peptides. On a longer time scale, T cells have to coordinate with one another to trigger a properly balanced immune response. Modeling this process is a daunting task because of the multiplicity of molecular and cellular interactions. I will show how phenotypic models can be built to describe those processes in a simple and predictive way. At the single cell level, we propose an « adaptive kinetic proofreading » model, detecting ligand strength irrespective of ligand concentrations. This model predicts experimental features such as ligand antagonism, which, interestingly, can be related to adversarial problems in artificial neural networks. At the cell population level, I will introduce a data driven approach to build phenomenological models of collective response, suggesting the existence of a simple cytokine code.

15 October 2020, 11am

Georges Debrégeas (Laboratoire Jean Perrin)

Persistent activities in the brain: from behavior to data-driven network models

Persistent neural activities are ubiquitous in neural systems. This capacity of networks to continuously discharge in the absence of on-going stimuli is believed to subserve short-term memorisation and temporal integration of sensory signals. Although persistence may reflect cellular mechanisms, it can also be a network emergent property. Here we investigate this latter mechanism on larval zebrafish, a model vertebrate that is accessible to brain-scale neuronal recording and high-throughput behavioral studies.

We thus combine behavioral assays, functional imaging and network modeling to understand the dynamics and function of a small bilaterally distributed neural circuit (ARTR). ARTR exhibits slow antiphasic alternations between its left and right subpopulation. This oscillation drives the coordinated orientation of the eyes and swim bouts, thus organizing the fish spatial exploration. The left/right transition can be induced through transient illumination of one eye such as to orient the fish towards towards light sources (phototaxis). We also show that the self-oscillatory frequency can be modulated by the water temperature. To elucidate the mechanism leading to the slow self-oscillation, we train a network (Ising) model on the neural recordings. The model allows us to generate synthetic oscillatory activity, whose features correctly captures the observed dynamics. It provides a simple physical interpretation of the persistent process.

8 October 2020, 11am

David Lacoste (Physico-Chimie Théorique, ESPCI)

Inequalities constraining fluctuations and fitness on lineage trees

We exploit a theoretical relation between two statistics on lineages trees, based either on forward lineages or on backward histories [1,2]. A fitness landscape is introduced, which quantifies the correlations between a trait of interest and the number of divisions. We derive various inequalities constraining the fluctuations of a trait of interest or its fitness on lineage trees. We apply this formalism to single-cell experiments with bacteria populations, carried out either in the mother machine configuration or in free conditions using time-lapse video-microscopy. We also investigate how the various sources of stochasticity at the single cell level can affect the population growth rate.

[1] Linking lineage and population observables in biological branching processes, R. Garcia-Garcia, A. Genthon and D. Lacoste, Phys. Rev. E, 042413 (2019).
[2] Fluctuation relations and fitness landscapes of growing cell populations, Scientific Reports, 10, 11889 (2020).