7.1.1 In@lgae

• Name: Numerical simulator of microalgae based processes
• Keywords: Simulation, Microalgae system, Productivity
• Functional Description: In@lgae simulates the productivity of a microalgae production system, taking into account both the process type and its location and time of the year. The process is mainly defined by its thermal dynamics and by its associated hydrodynamics. For a given microalgal strain, a set of biological parameters describe the response to nitrogen limitation, temperature and light. As a result, the biomass production, CO$_2$ and nitrogen fluxes, lipid and sugar accumulation are predicted.
• Release Contributions: The In@lgae platform has been optimised to make it faster. Some of the key models have been rewritten in C++ to allow a faster computation. Models have been improved to include, in the growth rate computation, the composition of the light spectrum. The graphical user interface has been enhanced and several sets of parameters describing different microalgal species have been stored.
• Authors: Étienne Delclaux, Francis Mairet, Olivier Bernard
• Contacts: Olivier Bernard, Francis Mairet
• Participants: Étienne Delclaux, Francis Mairet, Olivier Bernard, Quentin Béchet

7.1.2 Odin

• Name: Platform for advanced monitoring, control and optimisation of bioprocesses
• Keywords: Bioinformatics, Biotechnology, Monitoring, Automatic control
• Scientific Description:

  ODIN is a distributed application, whose graphical interfaces can be launched remotely through the Internet. The application, developed in Erlang, is architected around an MQTT broker. It is robust and tolerant to hardware failures in order to avoid that a wrong manipulation can have harmful consequences on the biotechnological process.

  Thus, the implementation of a new algorithm is done by a plugin written in Python language. Modifying one of these algorithms does not require recompiling the code.

  Translated with www.DeepL.com/Translator (free version)

• Functional Description: This application proposes a framework for on-line supervision of bioreactors. It gathers the data sampled from different on-line and off-line sensors. ODIN is a distributed platform, enabling remote monitoring as well as remote data acquisition.More originally, it enables researchers and industrials to easily develop and deploy advanced control algorithms, optimisation strategies, together with estimates of state variables or process state. It also contains a process simulator which can be harnessed for experimentation and training purposes. It is modular in order to adapt to any plant and to run most of the algorithms, and it can handle the high level of uncertainties that characterises the biological processes. The architecture is based on Erlang, and communication between modules through a MQTT Broker with Python for running the algorithms. ODIN is developed in collaboration with the INRIA Ibis research team.
• URL: https://team.inria.fr/biocore/software/odin/
• Authors: Nicolas Niclausse, Olivier Bernard, Eugenio Cinquemani, Tamas Muszbek, Thibaud Kloczko, Nicolas Chleq, Ghada Bahloul, Tristan Cabel, Francois Caddet, Jean-Luc Szpyrka, Pierre Fernique, Erwan Demairy, Amine Lahouel, Come Le Breton, Jonathan Levy, Julia Elizabeth Luna, Riham Nehmeh, Marc Vesin, Carlos Zubiaga Pena
• Contacts: Olivier Bernard, Eugenio Cinquemani, Nicolas Niclausse, Thibaud Kloczko
• Participants: Olivier Bernard, Nicolas Niclausse, Eugenio Cinquemani, Tamas Muszbek, Thibaud Kloczko, Nicolas Chleq, Jean-Luc Szpyrka, Pierre Fernique, Julia Elizabeth Luna, Come Le Breton, Jonathan Levy, Amine Lahouel, Tristan Cabel, Francois Caddet, Erwan Demairy, Riham Nehmeh, Marc Vesin, Carlos Zubiaga Pena

8.1.1 Mathematical study of ecological models

Participants: Frédéric Grognard, Ludovic Mailleret, Suzanne Touzeau, Clotilde Djuikem, Yves Fotso Fotso, Israël Tankam Chedjou.

Semi-discrete models. Semi-discrete models have shown their relevance in the modeling of biological phenomena whose nature presents abrupt changes over the course of their evolution 91. We used such models and analyzed their properties in several practical situations, some of them requiring such a modeling to describe external perturbations of natural systems such as harvest, and others to take seasonality into account. We developed these models in the context of augmentative introduction of species 1, seasonality in the dynamics of coffee leaf rust 80 and of banana and plantain burrowing nematodes 39, as well as for the protection of plant resistance against root-knot nematodes 37.

Models in plant epidemiology. We developed and analysed dynamical models describing plant-parasite interactions, in order to better understand, predict and control the evolution of damages in crops. We considered several pathosystems, further described in Section 8.6, describing and controlling the impact on plants of fungi 79, 40, nematodes 39, 37, and pests 84, 83.

8.1.2 Estimation and control

Participants: Frédéric Grognard, Ludovic Mailleret, Suzanne Touzeau, Yves Fotso Fotso, Samuel Nilusmas, Israël Tankam Chedjou.

Optimal control and optimisation. We developed several approaches to control the evolution of crop pests. To reduce crop losses due to plant-parasitic nematodes, we optimised (i) rotation strategies between resistant and susceptible cultivars of horticultural crops 37, or (ii) fallow periods between plantain cropping seasons 39. These optimisation problems were solved on a finite time horizon. They benefited from the resources and support of NEF computation cluster.

We also solved optimal control problem to limit the damages due to coffee berry borers 84, 83 and Coffee Leaf Rust 80 using the BOCOP software (https://www.bocop.org/).

8.2.1 Cell metabolism

Genetic variability in fruit sugar metabolism Predicting genotype-to-phenotype relationships is a big challenge for plant biology and breeding. Based on the model by Desnoues et al. 73, a reduction pipeline combining several reduction strategies has been developed to reduce both model size and nonlinearity and allow for further application to virtual breeding (collaboration with B. Quilot-Turion and Mohamed Memmah (INRAE Avignon) as part of the PhD thesis of Hussein Kanso). 29. In parallel, an inter-species comparison of fruit sugar metabolism has been conducted on ten contrasted species, including both starch-free and starch-rich species. Results showed distinct coordination among cellular processes in herbaceous and perennial plants, highligting different strategies for sugar accumulation 13.

8.2.2 Resource allocation

Modeling cell growth and resource allocation. The allocation of cellular resources can strongly influence not only the rate of cell growth but also the resulting cell size 69. To better investigate the connection between proteome allocation and cell volume, the original model by Giordano et al. 85 has been connected to a biophysical model of cell growth, explicitly describing cell volume increase as a function of cell's internal pressure and wall mechanical properties 87. In collaboration with I. Cheddadi (University of Grenoble) we are currently investigating the link between allocation to wall biosynthetic proteins and the resulting cell wall mechanics.

With F. Mairet (Ifremer Nantes) and H. de Jong (IBIS Grenoble), we also studied the influence of temperature on microbial growth laws 30.

Modeling energy constraints in microbial growth. In the framework of the Maximic project (collab. H. de Jong, IBIS team, and T. Gedeon, Montana State University) and as a follow up of our previous work 85, we developed a coarse-grained model of coupled energy and mass fluxes in microorganisms, based on minimal assumptions, and calibrate the model with data for E. coli. As reported in experimental data, the model predicts the occurrence of a growth rate-yield trade-off, as a generic property of the dependence of growth rate and growth yield on the distribution of resources over the production of ribosomes, enzymes in central metabolism and nutrient uptake, and enzymes in energy metabolism. An article is currently under preparation on this topic.

Optimal allocation of resources in a bacterium. We study by techniques of optimal control the optimal allocation between metabolism and gene expression during growth of bacteria, in collaboration with Inria IBIS and MCTAO project-teams. We developed different versions of the problem, and considered a new problem where the aim is to optimize the production of a product in a bioreactor 26, 49, (ANR project Maximic, PhD thesis of A. Yabo). The precise mathematical analysis of the optimal behavior (turnpike property) is under investigation 48.

8.2.3 Bacterial communities

A synthetic community of bacteria. In the framework of IPL Cosy (E. Cinquemani), we study the coexistence of two strains of bacteria E. Coli in a bioreactor. The strains have been modified synthetically to achieve some goals. The aim is to obtain a better productivity in the consortium than in a single strain, by control methods 34. We studied mathematical models of overflow metabolism (fermentative growth) in such bacteria 31, 46.

In collaboration with team VALSE (Lille), we also studied several problems of estimation and robust stabilization related to IPL Cosy, for two bacterial species in a bioreactor 21, 44, 22.

8.2.4 Synchronization and control using hybrid models

Participants: Nicolas Augier, Madalena Chaves, Jean-Luc Gouzé, Lucie Chambon, Agustín Yabo.

Hybrid control of genetic networks. We designed control strategies based on the measurement and control of a unique gene within positive or negative loops of genetic networks, in order to stabilize the system around its unstable fixed point. The quantized nature of genetic measurements and the new synthetic control approaches available in biology encourage the use of piecewise constant control laws. A specific partitioning of the state space and the study of successive repulsive regions allow to show global convergence and global stability for the resulting system. Several other control strategies are studied 18, 41. This is part of the PhD thesis of L. Chambon, and a collaboration with I. Belgacem and R. Edwards, University of Victoria.

Qualitative control for synchronization of piecewise linear systems We investigated the emergent dynamics in a network of $N$ coupled cells, each expressing a similar bistable switch 56. The bistable switch is modeled as a piecewise affine system and the cells are diffusively coupled. We show that both the coupling topology and the strength of the diffusion parameter may introduce new steady state patterns in the network. We study the synchronization properties of the coupled network and, using a control set of only three possible values ($u_{min}$, $u_{max}$, or 1), propose different control strategies which stabilize the system into a chosen synchronization pattern, both in the weak and strong coupling regimes.

Time-optimal control of piecewise affine bistable systems In 57 we give a geometric characterization of the time-optimal trajectories for a piecewise affine bistable switch, based on an adaptation of the Hybrid Pontryagin's Maximum Principle. Such hybrid models play a major role in systems biology, as they can expressively account for the behaviors of simple gene-regulatory networks.

8.2.5 State estimation with interval observers

Participants: Olivier Bernard, Frédéric Mazenc.

Dynamical systems involving Metzler matrices are convenient for designing interval observers. The necessary and sufficient condition ensuring that a real matrix of dimension 3 is similar to a Metzler matrix was exhibited. When this condition is satisfied, an interval observer for a family of continuous-time systems can be derived. We illustrated the interval observer design for the love dynamics in the case of limit cycles.

8.2.6 Modeling, analysis, and control for synthetic biology

Participants: Madalena Chaves, Eleni Firippi, Jean-Luc Gouzé, Hidde de Jong.

Coupling and synchronization of piecewise linear systems We considered a piecewise affine model of a synthetic two-gene oscillator and proved existence and stability of a periodic solution for all parameters in a given region 25. Motivated by the synchronization of circadian clocks in a cluster of cells, we next studied a network of $N$ identical oscillators under diffusive coupling. Our results show that both all-to-all and one-to-all coupling topologies may introduce new stable steady states, in addition to the expected periodic orbit. Both topologies admit an upper bound on the coupling parameter that prevents the generation of new steady states. However, this upper bound is independent of the number of oscillators in the network and less conservative for the one-to-all-topology. This is part of the PhD thesis of Eleni Firippi.

Period-control in a coupled system of two genetic oscillators In synthetic biology circuits it is important to improve system design and study robustness and control properties. Following our recent work  82, we consider a theoretic coupling scheme for the bidirectional interaction of two classic synthetic oscillators. Using different pairs of classic oscillators (an improved Smolen oscillator, coupled with either a cell cycle model or a repressilator), we compare the effect of the same coupling scheme on the period response of the coupled system, in terms of the properties of each individual oscillator. In our methodology we use computational tools and bifurcation analysis, to propose tuning of the coupling parameters and period control of the coupled circuit. This work is part of the PhD thesis of Eleni Firippi.

Review of qualitative analysis and control methods for synthetic circuits Qualitative modeling approaches are promising for the analysis and design of synthetic circuits, as they can make predictions of circuit behavior in the absence of precise, quantitative information. Moreover, they provide direct insight into the relation between the feedback structure and the dynamical properties of a network. In the book chapter 53, in collaboration with Hidde de Jong from the IBIS team, we reviewed the approaches of Boolean networks and piecewise-linear differential equations, and illustrate their application by means of three well-known synthetic circuits. We describe various methods for the analyis of state transition graphs, the discrete representations of the network dynamics that are generated in both modeling frameworks. We also briefly present the problem of controlling synthetic circuits, an emerging topic that could profit from the capacity of qualitative modeling approaches to rapidly scan a space of design alternatives.

8.3.1 Analysis and coupling of mammalian oscillators

Modeling, analysis and coupling of the mammalian cell cycle and clock A transcriptional model of the mammalian circadian clock was developed in 12 and its parameters calibrated against experimental data from F. Delaunay's lab. A cell cycle model was also previously developed by us 68. The interactions between the two oscillators are investigated under uni- or bi-directional coupling schemes 11. Numerical simulations replicate the oscillators' period-lock response and recover observed clock to cell cycle period ratios such as 1:1, 3:2 and 5:4 (as observed in experiments, F. Delaunay's lab). Moreover, for an uni-directional coupling scheme, we also investigate methods of slowing down the cell cycle by the use of clock modulating inputs, some of which correspond to existing drugs 24. This work is in collaboration with F. Delaunay (ANR ICycle) and was part of the PhD thesis of Sofia Almeida.

Analysis of asynchronous Boolean attractors: mammalian clock dynamics and robustness In asynchronous Boolean models, periodic solutions are represented by terminal strongly connected graphs (attractors), which are typically composed of hundreds of states and transitions. It is usually a challenging task to interpret the transitions inside an attractor in terms of the sequence of events in a biological cycle. Using a recent methodology to generate summary graphs  74 and a technique to find the attractors of coupled Boolean models 10, we studied a Boolean model of the mammalian circadian clock 42, for which the summary graph recovers the main phases of the cycle, in the expected order. It also suggests improvements in the design of the logical rules of the model and highlights groups of transitions that are essential for the attractor's robustness.

8.3.2 Modeling the apoptotic signaling pathway

A detailed model of the death receptor layer In a collaboration with J. Roux and within project Imodrez, the goal is to study the origins of cell-to-cell variability in response to anticancer drugs and provide a link between complex cell signatures and cell response phenotype. In a first approach, we constructed a detailed model to represent the death receptor-ligand binding and subsequent signaling cascade, with our previous PhD student Luis Gomes Pereira 45. This model was used to study the effect of intrinsic and extrinsic noise sources, and suggested the need to expand a set of reactions on the model, to account for the observed cell heterogeneity.

Core models of receptor reactions to evaluate basic pathway designs and heterogeneous response in apoptosis In a continued collaboration with J. Roux, we investigated the core reactions leading to caspase-8 activation, based on mass-action kinetics models, to evaluate the basic mechanisms giving rise to the observed heterogeneous response. To do this, we developed a group of core models with a minimal number of components and fitted them to single-cell trajectories of time-resolved caspase-8 activation measured in clonal cells after treatment with TRAIL 47. Several comparison and best fit measures were used to assess the relevance of each model and evaluate how well it captures the extent of biological heterogeneity observed in vitro. From this study, three points have a major role in establishing heterogeneity: a positive feedback loop on caspase-8, the impacts of initial condition variations and the relevance of the caspase-8 degradation. This is part of the work of the PhD student Marielle Péré.

Profiling the Non-genetic Origins of Cancer Drug Resistance We present fate-seq, a method coupling three single-cell technologies to associate the transcriptomic state of a cell to its predicted fate, based on cell response dynamics 35. The transcriptomic profiles showed an unexpected set of target genes that once perturbed, could all improve the cell sensitivity to the drug class tested. The study is relevant to cancer drug research, as cell-to-cell variability becomes a pertinent information during cancer clinical assessment. The PhD student L. Gomes-Pereira participated in this work from the Lab of J. Roux.

8.4.1 Modelling microalgae production

Participants: Olivier Bernard, Antoine Sciandra, Walid Djema, Francesca Casagli, David Demory, Bruno Assis Pessi, Liudi Lu, Jean-Philippe Steyer, Laetitia Giraldi.

Experimental developments

Running experiments in controlled dynamical environments. The experimental platform made of continuous photobioreactors driven by a set of automaton controlled by the ODIN software is a powerful and unique tool which gave rise to a quantity of very original experiments. Such platform improved knowledge of several biological processes such as lipid accumulation or cell cycle under light fluctuation, etc 51.

This experimental platform was used to control the long term stress applied to a population of microalgae using optimal control strategies20, 43. This Darwinian selection procedure generated several new strains more resistant to oxidative stresses after several months in the so called selectiostats 27.

On top of this, we carried out outdoor pilot experiments with solar light. We tested the impact of various temperatures, resulting from different shadowing configurations on microalgal growth rate.

Experimental work was also carried out in collaboration with the Inalve startup with microalgal biofilm to determine the impact of light and dark sequences on cell growth and photoacclimation. The architecture of the biofilms was also observed for different species with confocal microscopic techniques.

A review on the conditions for the production of lipids, their quality and their insustrial use was finally written in two book chapters 51, 54.

These works have been carried out in collaboration with A. Talec and E. Pruvost (CNRS/Sorbonne Université -Oceanographic Laboratory of Villefranche-sur-Mer LOV).

Metabolism of carbon storage and lipid production. A metabolic model has been set up and validated for the microalgae Chlorella vulgaris, on the basis of the DRUM framework , in order to simulate autotophic, heterotropic and mixotrophic growth, and to determine how to reduce substrate inhibition. The model was extended to other substrates such as glucose or glycerol. A simplified model was developed by I. Lopez to represent the dynamics of polar lipids, especially when faced to higher oxygen concentration. In particular, this model represents the microalgae growth under different conditions of temperature, light and oxygen.

Modeling the coupling between photosynthesis and hydrodynamics. We consider a coupled physical-biological model describing growth of microalgae in a raceway pond cultivation process, accounting for hydrodynamics. Our approach combines a biological model (based on the Han model) and shallow water dynamics equations that model the fluid into the raceway pond. We developped an optimization procedure dealing with the topography to maximize the biomass production over one lap or multiple laps with a paddle wheel. The results show that a flat topography is optimal in a periodic regime 58, 59. In other frameworks, non-trivial topographies can be obtained. We then studied the influence of mixing, assuming that a mixing device can redistribute the algae so that they can have access to light 61. A strategy to optimally mix the algae was derived. It was finally combined with the design of a non flat topography 60.

Modeling photosynthetic biofilms. Several models have been developed to represent the growth of microalgae within a biofilm. A first structured physiological model, extending the one proposed in 98 uses mixture theory to represent the microalgae growth, based on the consideration of intracellular reserves triggering the processes of growth, respiration and excretion. We consider separately the intracellular storage carbon (lipids and carbohydrates) and the functional part of microalgae . Another approach accounts for the dynamics of the light harvesting systems when cells are submitted to rapid successions of light and dark phases. A simpler model was developed and used to identify the optimal working mode of a process based on photosynthetic biofilm growing on a conveyor belt. The model was used to identify the worldwide potential of microalgal biofilms under different climates.

Modeling microalgae production processes. A model representing the dynamics of microalgae when growing in suboptimal conditions of light, nitrogen and phosphorus was developed. It consists in an extension of the Droop model accounting for the two quota of nitrogen and phosphorus. The model also represents the pigment acclimation to various light intensities. We have studied in 32 the response of a Droop model forced by periodic light or temperature signals. We transformed the model into a planar periodic system generating a monotone dynamical system. Combined with results on periodic Kolmogorov equations, the global dynamics of the system can be described.

Modeling thermal adaptation in microalgae. Experiments have been carried out in collaboration with A.-C. Baudoux (Biological Station of Roscoff) in order to study growth of various species of the microalgae genus Micromonas at different temperatures. After calibration of our models, we have shown that the pattern of temperature response is strongly related to the site where cells were isolated. We derived a relationship to extrapolate the growth response from isolation location. With this approach, we proved that the oceanwide diversity of Micromonas species is very similar to the oceanwide diversity of the phytoplankton 72. We have used Adaptive Dynamics theory to understand how temperature drives evolution in microalgae. We could then predict the evolution of this biodiversity in a warming ocean and show that phytoplankton must be able to adapt within 1000 generation to avoid a drastic reduction in biodiversity 72.

Modeling viral infection in microalgae. In collaboration with A.-C. Baudoux (Biological Station of Roscoff) a model was developed to account for the infection of a Micromonas population, with population of susceptible, infected and also free viruses. The model turned out to accurately reproduce the infection experiments at various temperatures, and the reduction of virus production above a certain temperature 63. The model was then extrapolated to the whole ocean to better understand how the warming will impact the mortality due to viruses.

8.4.2 Control and Optimization of microalgae production

Optimization of the bioenergy production systems A model predictive control algorithm was run based on simple microalgae models coupled with physical models where culture depth influences thermal inertia. Optimal operation in continuous mode for outdoor cultivation was determined when allowing variable culture depth. Assuming known weather forecasts considerably improved the control efficiency.

Interactions between species. We have proposed an optimal control strategy to select in minimal time the microalgal strain with the lowest pigment content 76. The control takes benefit from photoinhibition to compute light stresses penalizing the strains with a higher pigment content and finally selecting microalgae with lower chlorophyll content. Another optimal control problem was considered for selecting a strain of interest within two species competing for the same substrate, when dynamics is represented by a Droop model 77, 75, 78. In both cases, the optimal control derived from the Pontryagin maximum principle also exhibit a turnpike behaviour. This is a collaboration with team MCTAO.

Strategies to improve the temperature response have also been studied. We modelled the adaptive dynamics for a population submitted to a variable temperature 71. This was used at the LOV to design experiments with periodic temperature stresses aiming at enhancing polyunsaturated long chain fatty acids content of Tisochrysis lutea70.

8.4.3 Modelling mitochondrial inheritance patterns

Most eukaryotes inherit their mitochondria from only one of their parents. When there are different sexes, it is almost always the maternal mitochondria that are transmitted. Indeed, maternal uniparental inheritance has been reported for the brown alga Ectocarpus but we show in this study 95 that different strains of Ectocarpus can exhibit different patterns of inheritance: Ectocarpus siliculosus strains showed maternal uniparental inheritance, as expected, but crosses using different Ectocarpus species (7 strains) exhibited either paternal uniparental inheritance or an unusual pattern of transmission where progeny inherited either maternal or paternal mitochondria, but not both. A possible correlation between the pattern of mitochondrial inheritance and male gamete parthenogenesis was investigated. Moreover, in contrast to observations in the green lineage, we did not detect any change in the pattern of mitochondrial inheritance in mutant strains affected in life cycle progression. Finally, an analysis of field-isolated strains provided evidence of mitochondrial genome recombination in both Ectocarpus species.

8.5.1 Control and optimization of bioprocesses for depollution

Participants: Olivier Bernard, Carlos Martinez von Dossow, Jean-Luc Gouzé, Francesca Casagli.

We consider artificial ecosystems including microalgae, cyanobacteria and bacteria in interaction. The objective is to more efficiently remove inorganic nitrogen and phosphorus from wastewater, while producing a microalgal biomass which can be used for biofuel or bioplastic production. Models have been developed including predators grazing the microalgae.

Algae-bacteria processes for treating wastewater are becoming popular. We designed and calibrated a model, that was validated with more than one year of data 16. The model analysis revealed that despite pH regulation, a strong limitation for inorganic carbon was found to hinder the process efficiency and to generate conditions that are favorable for N2O emission. A control strategy regulating alkalinity turns out to be necessary to enhance the performance and avoid dammageable emissions 15.

8.5.2 Coupling microalgae to anaerobic digestion

Participants: Olivier Bernard, Antoine Sciandra, Jean-Philippe Steyer, Frédéric Grognard, Carlos Martinez von Dossow, Francesca Casagli.

The coupling between a microalgal pond and an anaerobic digester is a promising alternative for sustainable energy production and wastewater treatment by transforming carbon dioxide into methane using light energy. The ANR Phycover project is aiming at evaluating the potential of this process 99.

We have proposed several models to account for the biodiversity in the microalgal pond and for the interaction between the various species. These models were validated with data from the Saur company. More specifically, we have included in the miroalgae model the impact of the strong turbidity, and derived a theory to better understand the photolimitation dynamics especially when accounting for the photo-inhibition in the illuminated periphery of the reactor 93. Control strategies playing with the dilution rate, shadowing or modifying depth were then proposed 92.

8.5.3 Life Cycle Assessment

Participants: Olivier Bernard, Jean-Philippe Steyer, Marjorie Alejandra Morales Arancibia.

Environmental impact assessment. To follow up the pioneering life cycle assessment (LCA) work of  89, we identified the obstacles and limitations which should receive specific research efforts to make microalgae production environmentally sustainable 96.

We have studied the environmental impact of protein production from microalgae in an algal biofilm process and compared it to other sources (fisheries, soy,...). This study confirms the interest of microalgae for reducing the environmental impact 36.

This work is the result of a collaboration with Arnaud Helias of INRA-LBE (Laboratory of Environmental Biotechnology, Narbonne).

8.6.1 Controlling plant arthropod pests

Participants: Frédéric Grognard, Ludovic Mailleret, Suzanne Touzeau, Yves Fotso Fotso.

Optimization of introduction processes.

The question of how many and how frequently natural enemies should be introduced into crops to most efficiently fight a pest species is an important issue of integrated pest management. The topic of optimization of natural enemies introductions has been investigated for several years 90, and extends more generally to pulse perturbations in population dynamics. This year, our expertise allowed us to contribute to a review chapter on augmentative biological control 52, and we are currently writing a paper describing promising experimental results 81 on the combined use of food and artificial habitats supplementations to enhance augmentative biological control with predatory mites. This work has been performed in collaboration with Louise van Oudenhove (ISA).

Since this year, our research in this context expands to the modelling and optimization of introduction strategies in the context of the Sterile Insect Technique (SIT), thanks to the participation of the team in the project 'CeraTIS Corse', the first SIT pilot project in France focused on the control of an agricultural pest (the mediterranean fruit fly Ceratitis capitata).

Spatial population dynamics of biological control agents.

We have been involved for several years in a mixed modelling-experimental approach to explore the spatio-temporal dynamics of populations, with special interest to micro-wasp parasitoids 97, 88. In particular, we investigated, using computer simulation models and laboratory microcosms, how expanding populations can switch from 'pulled' to 'pushed' spatio-temporal dynamics when environmental connectivity decreases 62. Connected research has been performed on the influence of Allee effects and density dependence in dispersal on range shifts and the spatial pinning of populations, and on how Allee effects can increase population extinction risks 67. These works have been performed in collaboration with Elodie Vercken (ISA).

Concurrently, we are exploring the correlation between biological control agents movement caracteristics at different scales, from laboratory experimental caracterization to field dispersal. This research is performed on various species of parasitoids belonging to the genus Trichogramma, and is the main topic of Melina Cointe PhD thesis that started in autumn 2020 (director Vincent Calcagno, ISA).

Modelling and control of coffee berry borers.

We developed a model describing the coffee berry borer dynamics based on the insect life-cycle and the berry availability during a single cropping season. A control was introduced, based on a biopesticide (entomopathogenic fungus such as Beauveria bassiana) that is sprayed and persist on the berries. An optimal control problem was solved (see Section 8.1.2). The aim was to maximise the yield at the end of the cropping season, while minimising the borer population for the next cropping season and the control costs. Depending on the initial pest infestation, the optimal solution structure varied 83, 84. A PDE model taking the age of the berries and the preference of coffee berry borers for more mature berries was also developed. This research pertains to Yves Fotso Fotso's PhD thesis, who visited BIOCORE during 5 months in 2020 through the EPITAG associate team.

8.6.2 Controlling plant pathogens

Participants: Frédéric Grognard, Ludovic Mailleret, Suzanne Touzeau, Clotilde Djuikem.

Sustainable management of plant resistance.

We studied other plant protection methods dedicated to fight plant pathogens. One such method is the introduction of plant cultivars that are resistant to one pathogen. This often leads to the appearance of virulent pathogen strains that are capable of infecting the resistant plants.

We developed a spatio-temporal epidemiological model of the phoma stem canker of oilseed rape, to test and assess the durability of deployment strategies of various cultivars. We made this model more generic to represent several fungal diseases on annual field crops in a multi-pathogen context. Based on this model, we are developing a user-friendly, upgradeable and efficient simulation tool designed for researchers as well as non academic partners from technical institutes and agriculture cooperatives, thanks to the SiDRes AMDT. The first code sprint took place in October 2020 and produced a first validated tool, which is a solid base for future developements.

Coffee leaf rust (CLR) is a disease caused by a basidiomycete fungus, Hemileia vastatrix, that has a major impact on coffee production around the world. We produced a spatio-temporal model that describes CLR propagation in a coffee plantation during the rainy and dry seasons, and investigate numerically the impact of biocontrol 79. A multi-season hybrid model was also produced where the dry season was reduced to a discrete event; an optimal multi-season biological control for the pathogen control was then computed using the BOCOP software 80.

Taking advantage of plant diversity and immunity to minimize disease prevalence.

An epidemiological model of gene-for-gene interaction has been designed, considering increased defense to pathogen infections following previous exposure to a pathogen or an elicitor, namely priming. Priming provides a sort of immunity to virulent pathogens for resistant plants having undergone an infection attempt by an avirulent pathogen. This model showed that an optimal host mixture exists that ensures the lowest plant disease prevalence, so as to optimize the crop yield. It is especially efficient for pathogens with a low or intermediate basic reproduction rate and host plants with a high degree of priming 19. We are currently extending this work to take mixtures of different resistant strains and the possible presence of supervirulent pathogens. This was done in collaboration with Frédéric Hamelin (Agrocampus Ouest) in the framework of Pauline Clin's thesis that started in January 2020.

8.6.3 Plant-nematode interactions

Participants: Valentina Baldazzi, Frédéric Grognard, Ludovic Mailleret, Suzanne Touzeau, Israël Tankam Chedjou, Samuel Nilusmas.

Plant-parasitic nematodes are small little-mobile worms that feed and reproduce on plant roots, generating considerable losses in numerous crops all over the world. Most eco-friendly plant protection strategies are based on the use of resistant crops, but agricultural practices also contribute to nematode control.

Based on an interaction model between plantain roots and Radopholus similis, we built an impulsive model to compare two control strategies: pesticides, which are widely used, and the choice of the duration between cropping seasons (fallow deployment aimed at reducing the nematode population, followed by the plantation of a nursery-bought pest-free suckers, or vitroplant). Conditions on the pesticide load or the constant fallow duration are then derived to ensure the stability of the pest free equilibrium through the computation the effective reproduction number of pests 39. We then solved an optimisation problem (see Section 8.1.2) aimed at determining the variable fallow periods that maximise the farmer's cumulated yield, which is affected by the nematode population, while minimising the costs of nematode control and of the vitroplants purchase, on a fixed time horizon that lasts several cropping seasons 38. These results were extended to a situation where vitroplants are not planted every year, which reduces the costs, but also reduce the control efficiency 66 This research pertains to Israël Tankam Chedjou's PhD thesis, in the framework of the EPITAG associate team.

We also studied resistance-based root-knot nematode control. As virulent nematodes exhibit a reduced fitness on susceptible crops, alternating resistant and susceptible plants could help increase the efficiency and durability of such control methods. Optimal crop rotations (see Section 8.1.2) were characterised by low ratios of resistant plants and were robust to parameter uncertainty. Rotations provided significant gains over resistant-only strategies, especially for intermediate fitness costs and severe epidemic contexts. Switching from the current general deployment of resistant crops to custom rotation strategies could not only maintain or increase crop yield, but also preserve the few and valuable R-genes available. This research pertains to Samuel Nilusmas' PhD thesis, which he successfully defended in December 2020 and has been published this year 37. This work forms the theoretical foundations of a user-friendly interactive simulation tool aimed at non academic partners (agricultural profession and technical institutes) which has been produced within the Interlude project, and is available and can be accessed online : here.

Based on our previous work, an ecophysiological model of plant-nematode interaction has been extended to account for nematode population dynamics. In addition, the impact of root system architecture (RSA), via its effect on plant hydraulic conductivity and nematode infection probability, are currently under study.

8.6.4 Optimality/games in population dynamics

Participants: Frédéric Grognard, Ludovic Mailleret, Pierre Bernhard.

Optimal resource allocation.

Mycelium growth and sporulation are considered for phytopathogenic fungi. For biotrophic fungi, a flow of resource is uptaken by the fungus without killing its host; in that case, life history traits (latency-sporulation strategy) have been computed based on a simple model considering a single spore initiating the mycelium, several spores in competition and applying optimal resource allocation, and several spores in competition through a dynamic game through the analytico-numerical solution of the Hamilton-Jacobi-Bellman-Isaacs equation 40. This work is done with Fabien Halkett of INRA Nancy.

Optimal foraging and residence times variations.

In this work, we built on our re-analysis of the Marginal Value Theorem (MVT) 4 to study the effect on the optimal foraging strategy of habitat conversion, whereby patches are converted from one existing type to another, hence changing the frequency of each type in the environment. We studied how realized fitness and the average rate of movement should respond to changes in the frequency distribution of patch-types, and how they should covary. We found that the initial pattern of patch-exploitation in a habitat can help predict the qualitative responses of fitness and movement rate following habitat conversion. We concluded that taking into account behavioral responses may help better understand the ecological consequences of habitat conversion 14.

10.1.1 Inria International Labs

10.2.1 Visits of international scientists

• Yves Fotso Fotso, University of Dschang, Cameroon, February-July 2020. 6-month stay in the context of the EPITAG associate team, with the support of the AUF Collège doctoral régional de l’Afrique Centrale et des Grands Lacs “Mathématiques, Informatique, Biosciences et Géosciences de l’Environnement”.

10.2.2 Visits to international teams

10.3.1 National programmes

• ANR-PhotoBioFilm Explorer: The first objective of the PhotoBioFilm project (2021-2024) is to explore the activity of the molecules produced within a microalgam biofilm, and explaining its resistance to contamination. The second objective is to identify, characterize and produce novel biocompounds with benefits for human or animal health. The target is antibiotics, but other activities will be tested, especially antiviral activities. Biocore will be in charge of the biofilm modelling and the optimization of the production of the molecules of interests.
• ANR CtrlAB: The objectives of the Ctrl-AB project (2021-2024) are (i) to develop new control methods for the optimization of the productivity of a microbial community, and (ii) to demonstrate the effectiveness of these methods on a synthetic algal-bacterial consortium. Interestingly, co-culturing of E. coli with Chlorella leads to higher biomass and lipid productivity. Improved growth of Chlorella occurs despite competition of E. coli for the same substrates. On top of its ability to produce molecules like vitamins, which are necessary for algal growth, the bacteria also produce carbon dioxide (CO2), which is the substrate of the photosynthesis of the algae. The algae can produce oxygen (O2) fuelling bacterial growth, thus giving rise to a mutualistic pattern of interactions giving rise to several challenge for modelling anc controlling this artificial ecosystem.
• ANR-ICycle: This project (2016-2021) aims at understanding the communication pathways between the cell division cycle and the circadian clock, using mathematical modeling and control theory to construct and implement two coupled synthetic biological oscillators. Project coordinated by M. Chaves.
• ANR - Maximic: The goal of the project (2017-2021) is to design and implement control strategies in a bacterium for producing at maximal rate a high value product. It is coordinated by H. de Jong (IBIS Grenoble), and involves members of Biocore and McTao.
• Plan Cancer - Imodrez: The objective of this project (2018-2021) is to understand cancer drug response heterogeneity using tumor single-cell dynamics and developing mathematical models and computational approaches. A project coordinated by J. Roux (IRCAN) and funded by Inserm - Plan Cancer.
• SIGNALIFE: Biocore is part of this Labex (scientific cluster of excellence, 2nd period 2020-2024) whose objective is to build a network for innovation on Signal Transduction Pathways in life Sciences, and is hosted by the University Côte d'Azur.
• UMT FIORIMED: FioriMed is a Mixed Technology Unit created in January 2015 to strengthen the production and dissemination of innovation to the benefit of ornamental horticulture. Horticultural greenhouses are seen as a "laboratory" for the actual implementation of agroecology concepts with the possibility of generic outcomes being transfered to other production systems. The main partners of UMT FioriMed are ASTREDHOR (National Institute of Horticulture) and the ISA Joint Research Unit of INRA-CNRS-Univ. Nice.
• EcoPhyto - CeraTIS Corse: “Territorial management of the Mediterranean fruit fly in Corsica by the Sterile Insect Technique” (2020-2022). This project is based on a pilot field experiment of sterile male releases and it integrates population dynamics and socio-economic approaches.
• EcoPhyto - INTERLUDE: “Territorial innovations to reduce phytoparmaceutical products for the sustainable production of vegetable crops” (2020-2022). BIOCORE members participate in a case study that focuses on the agroecological management of soil pests and pathogens in Provence.
• ORACLE: ORACLE is a PGMO project (Gaspard Monge Program for Optimization) (2019-2020) using optimal control to solve problems of Optimal Resource Allocation in micro-­‐organisms under changing environment. It is coordinated by T. Bayen (University of Avignon).

10.3.2 Inria funding

• Inria Project Lab, Cosy: (2017-2021) This proposal aims at exploiting the potential of state-of-art biological modeling, control techniques, synthetic biology and experimental equipment to achieve a paradigm shift in control of microbial communities. We will investigate, design, build and apply an automated computer-driven feedback system for control of synthetic microbial communities, not just accounting for but rather leveraging population heterogeneity in the optimal accomplishment of a population-level task. The development of methodologies of general applicability will be driven by and applied to two different applications closely connected with real-world problems in the biomedical and biotechnological industry. The consortium is composed of the four Inria project-teams IBIS, BIOCORE, COMMANDS, VALSE, INBIO, as well as the external partners BIOP (Université Grenoble Alpes, including members of IBIS), MaIAge (INRA), and YoukLAB (TU Delft).
• AMDT, SiDRes: (2020-) The Action mutualisée de Développement Technologique “Simulateur pour le Déploiement de Résistances” aims at developing a user-friendly, upgradeable and efficient simulation tool to assess the durability of resistant cultivar deployment strategies. It focuses on the evolution of the interactions between fungal pathogens and annual field crop cultivars in an agricultural landscape. It involves the BIOCORE project-team and engineers from the SED, as well as INRAE colleagues.

10.3.3 INRAE funding

• ArchiNem: INRAE AgroEcoSystems is funding the project ArchiNem "Multi-scale modelling of plant nematode interactions: root architecture, plant physiology, nematode population dynamics and control" in which Biocore is a partner with INRAE Sophia Antipolis.
• MitesInn: INRAE SPE is funding the project MitesInn "Mites innovated: enhancing predatory mite based biological control with micro-habitats and alternative food" (2020-2021) in which Biocore is a partner with INRAE Sophia Antipolis.
• IMMUnE: INRAE SPE is funding the project IMMUnE "Immunité et Modélisation Mathématique pour Unifier l’Epidémiologie" (2019-2021), headed by F. Hamelin (Agrocampus Ouest), in which BIOCORE is a partner.

10.3.4 Networks

• Seminar: BIOCORE organizes a seminar “Modeling and control of ecosystems” at the station zoologique of Villefranche-sur-Mer, at INRAE-ISA or at Inria (quite irregular this year, and on-line).

11.1.1 Scientific events: organisation

11.1.2 Scientific events: selection

11.1.3 Journal

11.1.4 Invited talks

• M. Chaves gave a Keynote Lecture entitled “A feedback loop in apoptosis: its role in generating heterogeneity in cell response to cancer drugs” at the 4th SIGNALIFE Meeting (February, Nice, France)

11.1.5 Scientific expertise

• M. Chaves is a member of the Education Board of the Master “Quantitative and Computational Sciences for Biomedical data”, Université Côte d’Azur. She is also a member of the scientific committee of Labex Signalife (since 2020).
• J.-L. Gouzé is in the scientific committee of Académie 4 of UCA-Jedi. He is a member of the board of the SFBT (French Speaking Society for Theoretical Biology).
• O. Bernard is a member of the scientific committee of the Inalve company, represents Inria at the ANCRE (Alliance Nationale de Coordination de la Recherche pour l'Energie),represents Inria at the Scientific and Pedagogic committee of the UCA- EUR LIFE and is a member of the ADT (Technological Development Actions) commission at Inria.

11.1.6 Research administration

• O. Bernard, M. Chaves, and W. Djema are members of the CLDD of Inria SAM (local committee for sustainable development).
• M. Chaves (since 2020), L. Mailleret (since 2020) and F. Grognard (since 2015) are members of the INRAE Commission Scientifique Spécialisée (CSS) for Mathématique, Informatique, Sciences et Technologies du numérique, Intelligence artificielle et Robotique (MISTI), in charge of the research scientists evaluation at INRAE.
• J.-L. Gouzé is in the Inria committee supervising the doctoral theses, and a member of the scientific committee of Labex SIGNALIFE of Université Côte d'Azur, and of COREBIO PACA.
• F. Grognard is a member of the steering committee of Academy 3, Space, Environment, Risk and Resilience of UCA-JEDI. He is co-head of the development of the MSc Risk of UCA-JEDI and is a member of the Scientific Committee of the Agroecosystems department of INRAE.
• L. Mailleret is the head of the M2P2 team (Models and Methods for Plant Protection) of ISA. He’s in the Unit and scientific council of Institut Sophia Agrobiotech.
• L. Mailleret is an elected member (since 2020) of the Scientific and Pedagogic Council (CoSP) of the EUR LIFE (Graduate school in Life and Health Sciences ) of Université Côte d'Azur.
• S. Touzeau is a member of the steering committee of the INRAE metaprogramme SuMCrop “Sustainable Management of Crop Health”, a follow-up of the SMaCH metaprogramme (since 2016).

11.2.1 Teaching

• Licence: F. Grognard (45.5h ETD) and L. Mailleret (26h ETD), “Equations différentielles ordinaires et systèmes dynamiques”, L3, 1st year Engineering in Modeling and Applied Mathematics, Polytech Nice Sophia, Université Côte d'Azur, France.
• Master: O. Bernard (4.5h ETD), “Bioenergy from microalgae”, M2, Master International Energy Management : alternatives pour l'énergie du futur, Ecole Nationale Supérieure des Mines de Paris, France.
• Master: O. Bernard (18h ETD), “Modeling biotechnological processes”, M2, Ecole CentraleSupelec, Saclay, France.
• Master: O. Bernard (18h ETD), “Automatic Control applied to biotechnological processes”, M2, Ecole CentraleSupelec, Saclay, France.
• Master : J.-L. Gouzé (20.25h ETD), M. Chaves (13.5h ETD), “Modeling biological networks by ordinary differential equations”, M1, 2nd year Engineering in Génie biologique, Polytech Nice Sophia, Université Côte d'Azur, France.
• Master: F. Grognard (21h ETD) and L. Mailleret (21h ETD), “Bio-Mathématiques”, M1, 2nd year Engineering in Modeling and Applied Mathematics, Polytech Nice Sophia, Université Côte d'Azur, France.
• Master: F. Grognard (45h ETD), "Elements of mathematical modelling", M1, MSc in Environmental Hazards and Risks Management, Université Côte d'Azur, France.
• Professional formation: L. Mailleret (8h) "modélisation en dynamique des populations", internal formation INRAE.

11.2.2 Supervision

• PhD: L. Chambon. ”Control strategies for genetic feedback loops” , defended, Université Côte d’Azur. Supervisor J.-L. Gouzé.
• PhD: S. Nilusmas. “Gestion durable des nématodes à galles en cultures maraîchères : modélisation et optimisation du déploiement des résistances et des pratiques agronomiques”, Université Côte d'Azur, defended. Supervisors: S. Touzeau, C. Caporalino (ISA), V. Calcagno (ISA) and L. Mailleret.
• PhD: E. Firippi. “Mathematical analysis, control design and coupling for models of biological oscillators”, defended, Université Côte d'Azur. Supervisor: M. Chaves.
• PhD in progress: I. Tankam Chedjou. “Modeling, analysis and control of plantain plant-parasitic nematodes”, University of Yaoundé I, Cameroon, since December 2015. Supervisors: J.-J. Tewa (Univ. Yaoundé I), F. Grognard, L. Mailleret, S. Touzeau.
• PhD in progress: Y. Fotso Fotso. “Modeling, analysis and control of coffee berry borers”, University of Dschang, Cameroon, since January 2017. Supervisors: B. Tsanou (Univ. Dschang), S. Bowong (Univ. Douala), F. Grognard, S. Touzeau.
• PhD in progress: M. Gachelin. “Selection pressure to improve lipid productivity of microalgae”, since March 2017, UPMC. Supervisors: O. Bernard and A. Sciandra.
• PhD in progress: F. Aubrée “Modélisation de l'adaptation des populations aux fortes pressions anthropiques”, Université Côte d'Azur, since 2017. V. Calcagno, T. Guillemaud, L. Mailleret.
• PhD in progress: A. Yabo. “Control and optimal control of bacterial growth”, since October 2018, Université Côte d'Azur. Supervisors J.-L. Gouzé and J.-B. Caillau (team McTao).
• PhD in progress: A. Dos Reis de Souza. “Estimation and Control Methods for Microbial Communities”, since October 2018, Université de Lille. Supervisors: J.-L. Gouzé and D. Efimov (team Valse, Inria Lille).
• PhD in progress: B. Assis Pessi. “Modelling and Control of outdoor microalgal processes”, since November 2019, Université Côte d'Azur. Supervisors: O. Bernard and L. Giraldi (team McTao).
• PhD in progress: C. Djuikem. “Modelling and control of perennial plant phytopathogens”, Université Côte d'Azur, since October 2019. Supervisors: F. Grognard, S. Touzeau, S. Bowong (Univ. Douala).
• PhD in progress: M. Péré. “'Modeling cancer drug response heterogeneity using experimental tumor single-cell dynamics and transcriptomics', since October 2019, Université Côte d'Azur. Supervisors: M. Chaves and J. Roux (IRCAN, Nice).
• PhD in progress: P. Clin, "Immunity and Mathematical Modelling to ”Unify” Epidemiology", since January 2020, Université de Rennes 1. Supervisors: F. Hamelin, L. Mailleret, D. Andrivon.
• PhD in progress: M. Cointe. “Mieux prédire la propagation spatiale de groupes de trichogrammes pour améliorer le biocontrôle : de l’écologie du mouvement à la dispersion dans les cultures”, Université Côte d'Azur, since 2020. V. Calcagno, L. Mailleret.

11.2.3 Master thesis and internships

• L3: Jessica Gourdon, "Lockdown optimization for Covid-19 control", Polytech Nice Sophia, Université Côte d'Azur, MAM3, supervisors: F. Grognard and L. Mailleret
• M2: J. Nardini, “Supplémentation et lutte biologique : Booster le biocontrôle des acariens prédateurs”. Aix-Marseille Université. Supervisors : Louise van Oudenhove (ISA) L. Mailleret.
• M1: F. Ghesthem, “Caractérisation et modélisation de stratégies de gestion durable des populations de nématodes à galles Meloidogyne incognita”. Institut Agro. Supervisors : V. Calcagno (ISA) L. Mailleret, S. Touzeau.
• M2: L. Plaza Alvarez, “Microalgae growth limited by light, nitrogen, and phosphorus”. Universidad Técnica Federico Santa María, Valparaiso. Supervisors: C. Martinez von Dossow and O. Bernard.
• Other: A. Yabo supervised the short internship (projet) of 4 students from EPU MAM4, concerning optimal control of a biological model of growth.
• Other: O. Bernard supervised a project involving 4 students from CentraleSupelec (first year of engineering school), 4 months, to design a system for microalgae growing under biofilm forms.
• Other: L. Giraldi, F. Grognard and L. Mailleret supervised a project involving 3 students from Polytech Nice Sophia, Université Côte d'Azur, MAM4 to design and fit an epidemiological model on Covid-19 data.

11.2.4 Juries

• O. Bernard was referee for the jury of the PhD thesis of Angela La, “Process development for symbiotic culture of Saccharomyces cerevisiae and Chlorella vulgaris for in situ CO${}_2$ mitigation”. University Paris-Saclay (May, 22nd 2019).
• M. Chaves was in the PhD jurys of: Daniel Figueiredo (as examiner; February, Univ. Aveiro, Portugal), Ousmane Diop (as president of the jury; December, Univ. Paris-Saclay), Eleni Firippi (as advisor; December, Université Côte d'Azur), Yacine El Alaoui-Faris (as president of the jury; December, Université Côte d'Azur).
• M. Chaves was in the Master jury of Mariana Mota as main examiner (January 2021, Instituto Superior Técnico, Portugal)
• M. Chaves is in the PhD committees of Agustin Yabo (STIC, Université Côte d'Azur) and Sandra Kovachka (BoostUrCareer program, Université Côte d'Azur)
• J.-L. Gouzé was reviewer of the HDR of Radhouene Fekih Salem, July, University of Tunis El Manar, Tunisia, and a member of the jury for the PhD thesis of José Plaza, January, ULB Belgique, of Aïda Feddaoui-Papin, May, University of Toulon, of Nelson de Figueiredo Barroso, December, University of Lille, of Lucie Chambon, September, Université Côte d'Azur.
• L. Mailleret was in the PhD Jury of Samuel Nilusmas (as advisor). Université Côte d'Azur, Décembre 2020.
• J.-L. Gouzé is in the PhD committees of P. Jacquet (Univ. Grenoble) and A. Pavlou (Univ. Grenoble).
• F. Grognard and S. Touzeau are in the thesis committee of Pauline Clin (Universoité de Rennes 1) on "Immunity and Mathematical Modelling to ”Unify” Epidemiology".
• F. Grognard is in the thesis committee of Méline Saubin (Université de Lorraine) on "Effets de la démographie sur la structure de populations dans le cadre d'une maladie émergente".
• S. Touzeau was a member of selection boards for the recruitment of junior research scientists at INRAE in applied mathematics, computer science, economics and social sciences (7 positions).

11.2.5 Internal or external Inria responsibilities

• Eleni Firippi was part of the organizing committee of the "PhD Seminars," dedicated to meetings and presentations among the doctoral students at Inria Sophia Antipolis. She helped organize MOMI2020 "Le Monde des Mathematiques Industrielles," a workshop bringing together young researchers in mathematics and industrial applications.

International journals

• 11 articleSofiaS. Almeida, MadalenaM. Chaves and FranckF. Delaunay. Control of synchronization ratios in clock/cell cycle coupling by growth factors and glucocorticoidsRoyal Society Open Science722020, 192054
  HALDOIback to text
• 12 articleSofiaS. Almeida, MadalenaM. Chaves and FranckF. Delaunay. Transcription-based circadian mechanism controls the duration of molecular clock states in response to signaling inputsJournal of Theoretical Biology484January 2020, 110015
  HALDOIback to text
• 13 articleCoffi BelmysC. Cakpo, GillesG. Vercambre, ValentinaV. Baldazzi, LéaL. Roch, ZhanwuZ. Dai, PierreP. Valsesia, Mohamed-MahmoudM.-M. Memah, SophieS. Colombie, AnnickA. Moing, YvesY. Gibon and MichelM. Génard. Model-assisted comparison of sugar accumulation patterns in ten fleshy fruits highlights differences between herbaceous and woody speciesAnnals of Botany12632020, 455-470
  HALDOIback to text
• 14 articleVincentV. Calcagno, Frédéric MarieF. Hamelin, LudovicL. Mailleret and FrédéricF. Grognard. How optimal foragers should respond to habitat changes: on the consequences of habitat conversionTheoretical Ecology132June 2020, 165-175
  HALDOIback to text
• 15 article FrancescaF. Casagli, SimoneS. Rossi, Jean-PhilippeJ.-P. Steyer, OlivierO. Bernard and ElenaE. Ficara. Balancing microalgae and nitrifiers for wastewater treatment: can inorganic carbon limitation cause an environmental threat? Environmental Science and Technology February 2021
  HAL back to text back to text
• 16 articleFrancescaF. Casagli, GaetanoG. Zuccaro, OlivierO. Bernard, Jean-PhilippeJ.-P. Steyer and ElenaE. Ficara. ALBA: A comprehensive growth model to optimize algae-bacteria wastewater treatment in raceway pondsWater Research190February 2021, 116734
  HALDOIback to textback to text
• 17 articleFrancescaF. Casagli, GaetanoG. Zuccaro, OlivierO. Bernard, Jean-PhilippeJ.-P. Steyer and ElenaE. Ficara. ALBA: a comprehensive growth model to optimize algae-bacteria wastewater treatment in raceway pondsWater Research190February 2021, 116734
  HALDOI
• 18 articleLucieL. Chambon, IsmailI. Belgacem and Jean-LucJ.-L. Gouzé. Qualitative control of undesired oscillations in a genetic negative feedback loop with uncertain measurementsAutomatica112February 2020, 108642
  HALDOIback to text
• 19 article PaulineP. Clin, FrédéricF. Grognard, LudovicL. Mailleret, FlorenceF. Val, DidierD. Andrivon and Frédéric MarieF. Hamelin. Taking advantage of pathogen diversity and immune priming to minimize disease prevalence in host mixtures: a model Phytopathology December 2020
  HAL DOI back to text back to text
• 20 articleWalidW. Djema, OlivierO. Bernard and LaetitiaL. Giraldi. Separating Two Species of Microalgae in Photobioreactors in Minimal TimeJournal of Process Control87March 2020, 120-129
  HALDOIback to text
• 21 articleAlexA. Dos Reis De Souza, DenisD. Efimov, AndreyA. Polyakov and Jean-LucJ.-L. Gouzé. Robust Stabilization of Competing Species in the ChemostatJournal of Process Control872020, 138-146
  HALDOIback to text
• 22 articleAlexA. Dos Reis De Souza, Jean-LucJ.-L. Gouzé, DenisD. Efimov and AndreyA. Polyakov. Robust Adaptive Estimation in the Competitive ChemostatComputers & Chemical Engineering142November 2020, 107030
  HALDOIback to text
• 23 articlePaulineP. Ezanno, MathieuM. Andraud, GaëlG. Beaunée, ThierryT. Hoch, S. Krebs, ArnaudA. Rault, SuzanneS. Touzeau, ElisabetaE. Vergu and StefanS. Widgren. How mechanistic modelling supports decision making for the control of enzootic infectious diseasesEpidemics32September 2020, 100398
  HALDOI
• 24 articleSofia JoséS. Figueiredo Almeida, MadalenaM. Chaves and FranckF. Delaunay. Cell cycle period control through modulation of clock inputsJournal of Bioinformatics and Computational Biology1803June 2020, 2040006
  HALDOIback to text
• 25 articleElenaE. Firippi and MadalenaM. Chaves. Topology-induced dynamics in a network of synthetic oscillators with piecewise affine approximationChaos: An Interdisciplinary Journal of Nonlinear Science3011November 2020, 113128
  HALDOIback to text
• 26 articleAgustínA. Gabriel Yabo, Jean-BaptisteJ.-B. Caillau and Jean-LucJ.-L. Gouzé. Optimal bacterial resource allocation: metabolite production in continuous bioreactorsMathematical Biosciences and Engineering1762020, 7074-7100
  HALDOIback to text
• 27 article ManonM. Gachelin, MarcM. Boutoute, GregoryG. Carrier, AmélieA. Talec, EricE. Pruvost, FreddyF. Guihéneuf, OlivierO. Bernard and AntoineA. Sciandra. Enhancing PUFA-rich polar lipids in Tisochrysis lutea using adaptive laboratory evolution (ALE) with oscillating thermal stress Applied Microbiology and Biotechnology November 2020
  HAL DOI back to text
• 28 article FrédéricF. Jean, SofyaS. Maslovskaya and IgorI. Zelenko. On Weyl's type theorems and genericity of projective rigidity in sub-Riemannian Geometry Geometriae Dedicata 2020
  HAL
• 29 articleHusseinH. Kanso, BénédicteB. Quilot-Turion, Mohamed-MahmoudM.-M. Memah, OlivierO. Bernard, Jean-LucJ.-L. Gouzé and ValentinaV. Baldazzi. Reducing a model of sugar metabolism in peach to catch different patterns among genotypesMathematical Biosciences321March 2020, 108321
  HALDOIback to text
• 30 article FrancisF. Mairet, Jean-LucJ.-L. Gouzé and HiddeH. De Jong. Optimal proteome allocation and the temperature dependence of microbial growth laws npj Systems Biology and Applications 2021
  HAL back to text
• 31 article CarlosC. Martínez and Jean-LucJ.-L. Gouzé. Global dynamics of the chemostat with overflow metabolism Journal of Mathematical Biology 82 3 February 2021
  HAL DOI back to text
• 32 article CarlosC. Martinez, FrancisF. Mairet and OlivierO. Bernard. Dynamics of the periodically forced light-limited Droop model Journal of Differential Equations April 2020
  HAL DOI back to text
• 33 article CarlosC. Martinez, FrancisF. Mairet, LeslieL. Meier, DavidD. Jeison and AndrésA. Avila. Modeling and analysis of an Absorption Column Connected to a Microalgae Culture SIAM Journal on Applied Mathematics 2020
  HAL
• 34 articleMarcoM. Mauri, Jean-LucJ.-L. Gouzé, HiddeH. De Jong and EugenioE. Cinquemani. Enhanced production of heterologous proteins by a synthetic microbial community: Conditions and trade-offsPLoS Computational Biology1642020, e1007795
  HALDOIback to textback to text
• 35 articleMickaelM. Meyer, AgnèsA. Paquet, Marie-JeanneM.-J. Arguel, LudovicL. Peyre, LuisL. Gomes-Pereira, KevinK. LeBrigand, BahariaB. Mograbi, PatrickP. Brest, RainerR. Waldmann, PascalP. Barbry, PaulP. Hofman and JérémieJ. Roux. Profiling the Non-genetic Origins of Cancer Drug Resistance with a Single-Cell Functional Genomics Approach Using Predictive Cell DynamicsCell Systems114October 2020, 367-374
  HALDOIback to text
• 36 articleMarjorieM. Morales, HubertH. Bonnefond and OlivierO. Bernard. Rotating algal biofilm versus planktonic cultivation: LCA perspectiveJournal of Cleaner Production257June 2020, 120547
  HALDOIback to text
• 37 articleSamuelS. Nilusmas, MathildeM. Mercat, ThomasT. Perrot, CarolineC. Djian‐Caporalino, PhilippeP. Castagnone‐Sereno, Suzanne S.S. Touzeau, VincentV. Calcagno and LudovicL. Mailleret. Multi‐seasonal modelling of plant‐nematode interactions reveals efficient plant resistance deployment strategiesEvolutionary Applications1392020, 2206-2221
  HALDOIback to textback to textback to textback to text
• 38 articleIsraëlI. Tankam-Chedjou, FrédéricF. Grognard, Jean JulesJ. Tewa and SuzanneS. Touzeau. Optimal and sustainable management of a soilborne banana pestApplied Mathematics and Computation397May 2021, 125883
  HALDOIback to text
• 39 articleIsraëlI. Tankam-Chedjou, Suzanne S.S. Touzeau, LudovicL. Mailleret, Jean JulesJ. Tewa and FrédéricF. Grognard. Modelling and control of a banana soilborne pest in a multi-seasonal frameworkMathematical Biosciences322April 2020, 108324
  HALDOIback to textback to textback to textback to text
• 40 articleIvanI. Yegorov, FrédéricF. Grognard, Ludovic L.L. Mailleret, FabienF. Halkett and PierreP. Bernhard. A dynamic game approach to uninvadable strategies for biotrophic pathogensDynamic Games and Applications102020, 257-296
  HALDOIback to textback to text

International peer-reviewed conferences

• 41 inproceedings IsmailI. Belgacem, Jean-LucJ.-L. Gouzé and RoderickR. Edwards. Control of negative feedback loops in genetic networks CDC 2020 - 59th Conference on Decision and Control Jeju Island, South Korea December 2020
  HAL back to text
• 42 inproceedingsOusmaneO. Diop, MadalenaM. Chaves and LaurentL. Tournier. Qualitative Analysis of Mammalian Circadian Oscillations: Cycle Dynamics and RobustnessCMSB 2020 - 18th International Conference on Computational Methods in Systems BiologyKonstanz, GermanySeptember 2020, 176-192
  HALDOIback to text
• 43 inproceedings WalidW. Djema, OlivierO. Bernard and TérenceT. Bayen. Optimal control separating two microalgae species competing in a chemostat CDC 2020 - 59th IEEE Conference on Decision and Control 2020 59th IEEE Conference on Decision and Control (CDC) Jeju Island, South Korea December 2020
  HAL back to text
• 44 inproceedings AlexA. Dos Reis De Souza, DenisD. Efimov, AndreyA. Polyakov and Jean-LucJ.-L. Gouzé. Observer-Based Robust Control of a Continuous Bioreactor with Heterogeneous Community IFAC 2020 - 21rst IFAC World Congress Berlin / Virtual, Germany July 2020
  HAL back to text
• 45 inproceedings LuisL. Gomes-Pereira, MadalenaM. Chaves and JérémieJ. Roux. A model of apoptosis receptor reactions to study cell fate decision IEEE Xplore MED 2020 - 28th Mediterranean Conference on Control and Automation Saint Raphaël, France September 2020
  HAL back to text
• 46 inproceedings CarlosC. Martinez and Jean-LucJ.-L. Gouzé. Optimal control of a fed-batch reactor with overflow metabolism IFAC 2020 - 1st Virtual World Congress by the International Federation of Automatic Control Berlin, Germany July 2020
  HAL back to text
• 47 inproceedingsMarielleM. Péré, MadalenaM. Chaves and JérémieJ. Roux. Core Models of Receptor Reactions to Evaluate Basic Pathway Designs Enabling Heterogeneous Commitments to ApoptosisLecture Notes in Computer ScienceCMSB 2020 - 18th International Conference on Computational Methods in Systems Biology12314Konstanz, GermanySeptember 2020, 298-320
  HALDOIback to text

Conferences without proceedings

• 48 inproceedings Jean-BaptisteJ.-B. Caillau, WalidW. Djema, LaetitiaL. Giraldi, Jean-LucJ.-L. Gouzé, SofyaS. Maslovskaya and Jean-BaptisteJ.-B. Pomet. The turnpike property in maximization of microbial metabolite production IFAC 2020 - 21rst IFAC World Congress Berlin / Virtual, Germany July 2020
  HAL back to text
• 49 inproceedings AgustínA. Gabriel Yabo and Jean-LucJ.-L. Gouzé. Optimizing bacterial resource allocation: metabolite production in continuous bioreactors IFAC 2020 - 1st Virtual World Congress by the International Federation of Automatic Control Berlin / Virtual, Germany July 2020
  HAL back to text
• 50 inproceedings NayatN. Sanchez-Pi, LuisL. Marti, AndréA. Abreu, OlivierO. Bernard, ColombanC. de Vargas, DamienD. Eveillard, AlejandroA. Maass, Pablo A.P. Marquet, JacquesJ. Sainte-Marie, JulienJ. Salomon, MarcM. Schoenauer and MicheleM. Sebag. Artificial Intelligence, Machine Learning and Modeling for Understanding the Oceans and Climate Change NeurIPS 2020 Workshop - Tackling Climate Change with Machine Learning Santiago / Virtual, Chile December 2020
  HAL

Scientific book chapters

• 51 inbook HubertH. Bonnefond, CharlotteC. Combe, Jean-PaulJ.-P. Cadoret, AntoineA. Sciandra and OlivierO. Bernard. Potentiel des microalgues Chimie verte et industries agroalimentaires - Vers une bioéconomie durable February 2020
  HAL back to text back to text
• 52 inbookAlexandreA. Bout, NicolasN. Ris, CéciliaC. Multeau and LudovicL. Mailleret. Lutte biologique par augmentation à l’aide d’arthropodes entomophages contre les arthropodes phytophagesBiocontrôle. Éléments pour une protection agroécologique des cultures.Savoir Faire (Quae)https://www.quae.com2020, 376 p.
  HALback to text
• 53 inbook MadalenaM. Chaves and HiddeH. De Jong. Qualitative modeling, analysis, and control of synthetic regulatory circuits Synthetic Gene Circuits: Methods and Protocols Methods in Molecular Biology January 2021
  HAL back to text
• 54 inbookJelena HeleneJ. Cvejic, Antonio LucaA. Langellotti, HubertH. Bonnefond, VitoV. Verardo and OlivierO. Bernard. Microalgae as a source of edible oilsLipids and Edible Oils2020, 175-211
  HALDOIback to text

Reports & preprints

• 55 misc NicolasN. Augier, UgoU. Boscain and MarioM. Sigalotti. Effective adiabatic control of a decoupled Hamiltonian obtained by rotating wave approximation January 2021
  HAL
• 56 misc NicolasN. Augier, MadalenaM. Chaves and Jean-LucJ.-L. Gouzé. Qualitative control strategies for synchronization of bistable gene regulatory networks September 2020
  HAL back to text
• 57 misc NicolasN. Augier and Agustín GabrielA. Yabo. Time-optimal control of piecewise affine bistable gene-regulatory networks: preliminary results January 2021
  HAL back to text
• 58 misc OlivierO. Bernard, Liu-diL.-d. Lu, JacquesJ. Sainte Marie and JulienJ. Salomon. Shape optimization of a microalgal raceway to enhance productivity November 2020
  HAL back to text
• 59 misc OlivierO. Bernard, Liu-diL.-d. Lu, JacquesJ. Sainte-Marie and JulienJ. Salomon. Controlling the bottom topography of a microalgal pond to optimize productivity 2020
  HAL back to text
• 60 misc OlivierO. Bernard, Liu-diL.-d. Lu and JulienJ. Salomon. Mixing strategies combined with shape design to enhance productivity of a raceway pond November 2020
  HAL back to text
• 61 misc OlivierO. Bernard, Liu-diL.-d. Lu and JulienJ. Salomon. Optimizing microalgal productivity in raceway ponds through a controlled mixing device 2020
  HAL back to text
• 62 misc MaximeM. Dahirel, AlineA. Bertin, MarjorieM. Haond, AurélieA. Blin, EricE. Lombaert, VincentV. Calcagno, SimonS. Fellous, LudovicL. Mailleret, ThibautT. Malausa and ElodieE. Vercken. Shifts from pulled to pushed range expansions caused by reduction of landscape connectedness May 2020
  HAL DOI back to text
• 63 misc DavidD. Demory, JoshuaJ. Weitz, A-CA.-C. Baudoux, SuzanneS. Touzeau, NatalieN. Simon, SophieS. Rabouille, AntoineA. Sciandra and OlivierO. Bernard. A thermal trade-off between viral production and degradation drives phytoplankton-virus population dynamics December 2020
  HAL DOI back to text
• 64 misc RémiR. Robin, NicolasN. Augier, UgoU. Boscain and MarioM. Sigalotti. On the compatibility of the adiabatic and rotating wave approximations for robust population transfer in qubits March 2020
  HAL
• 65 misc IsraëlI. Tankam-Chedjou, FrédéricF. Grognard, Jean JulesJ. Tewa and SuzanneS. Touzeau. Optimal and sustainable management of a soilborne banana pest July 2020
  HAL
• 66 misc IsraëlI. Tankam-Chedjou, FrédéricF. Grognard, Jean-JulesJ.-J. Tewa and SuzanneS. Touzeau. When and how to fallow: first steps towards banana crop yield improvement through optimal and sustainable control of a soilborne pest January 2021
  HAL back to text
• 67 misc ElodieE. Vercken, GéraldineG. Groussier, LaurentL. Lamy and LudovicL. Mailleret. The hidden side of the Allee effect: correlated demographic traits and extinction risk in experimental populations May 2020
  HAL back to text