Synthetic associative learning in engineered multicellular consortia

Associative learning is one of the key mechanisms displayed by living organisms in order to adapt to their changing environments. It was early recognized to be a general trait of complex multicellular organisms but also found in "simpler" ones. It has also been explored within synthetic biology using molecular circuits that are directly inspired in neural network models of conditioning. These designs involve complex wiring diagrams to be implemented within one single cell and the presence of diverse molecular wires become a challenge that might be very difficult to overcome. Here we present three alternative circuit designs based on two-cell microbial consortia able to properly display associative learning responses to two classes of stimuli and displaying long and short-term memory (i. e. the association can be lost with time). These designs might be a helpful approach for engineering the human gut microbiome or even synthetic organoids, defining a new class of decision-making biological circuits capable of memory and adaptation to changing conditions. The potential implications and extensions are outlined.Comment: 5 figure

On Dynamics and Invariant Sets in Predator-Prey Maps

A multitude of physical, chemical, or biological systems evolving in discrete time can be modelled and studied using difference equations (or iterative maps). Here we discuss local and global dynamics for a predator-prey two-dimensional map. The system displays an enormous richness of dynamics including extinctions, co-extinctions, and both ordered and chaotic coexistence. Interestingly, for some regions we have found the so-called hyperchaos, here given by two positive Lyapunov exponents. An important feature of biological dynamical systems, especially in discrete time, is to know where the dynamics lives and asymptotically remains within the phase space, that is, which is the invariant set and how it evolves under parameter changes. We found that the invariant set for the predator-prey map is very sensitive to parameters, involving the presence of escaping regions for which the orbits go out of the domain of the system (the species overcome the carrying capacity) and then go to extinction in a very fast manner. This theoretical finding suggests a potential dynamical fragility by which unexpected and sharp extinctions may take place

About ghost transients in spatial continuous media

Altres ajuts: acords transformatius de la UABThe impact of space on ecosystem dynamics has been a matter of debate since the dawn of theoretical ecology. Several studies have revealed that space usually involves an increase in transients' times, promoting the so-called supertransients. However, the effect of space and diffusion in transients close to bifurcations has not been thoroughly investigated. In non-spatial deterministic models such as those given by ordinary differential equations transients become extremely long in the vicinity of bifurcations. Specifically, for the saddle-node (s-n) bifurcation the time delay, τ, follows τ∼|μ−μ|; μ and μ being the bifurcation parameter and the bifurcation value, respectively. Such long transients are labeled delayed transitions and are governed by the so-called ghosts. Here, we explore a simple model with intra-specific cooperation (autocatalysis) and habitat loss undergoing a s-n bifurcation using a partial differential equations (PDE) approach. We focus on the effects of diffusion in the ghost extinction transients right after the tipping point found at a critical habitat loss threshold. Our results show that the bifurcation value does not depend on diffusion. Despite transients' length typically increase close to the bifurcation, we have observed that at extreme values of diffusion, both small and large, extinction times remain long and close to the well-mixed results. However, ghosts lose influence at intermediate diffusion rates, leading to a dramatic reduction of transients' length. These results, which strongly depend on the initial size of the population, are shown to remain robust for different initial spatial distributions of cooperators. A simple two-patch metapopulation model gathering the main results obtained from the PDEs approach is also introduced and discussed. Finally, we provide analytical results of the passage times and the scaling for the model under study transformed into a normal form. Our findings are discussed within the framework of ecological transients

Habitat loss causes long extinction transients in small trophic chains

Transients in ecology are extremely important since they determine how equilibria are approached. The debate on the dynamic stability of ecosystems has been largely focused on equilibrium states. However, since ecosystems are constantly changing due to climate conditions or to perturbations driven by the climate crisis or anthropogenic actions (habitat destruction, deforestation, or defaunation), it is important to study how dynamics can proceed till equilibria. This article investigates the dynamics and transient phenomena in small food chains using mathematical models. We are interested in the impact of habitat loss in ecosystems with vegetation undergoing facilitation. We provide a dynamical study of a small food chain system given by three trophic levels: primary producers, i.e., vegetation, herbivores, and predators. Our models reveal how habitat loss pushes vegetation towards tipping points, how the presence of herbivores in small habitats could promote ecosystem's extinction (ecological meltdown), or how the loss of predators produce a cascade effect (trophic downgrading). Mathematically, these systems exhibit many of the possible local bifurcations: saddle-node, transcritical, Andronov-Hopf, together with a global bifurcation given by a heteroclinic bifurcation. The associated transients are discussed, from the ghost dynamics to the critical slowing down tied to the local and global bifurcations. Our work highlights how the increase of ecological complexity (trophic levels) can imply more complex transitions. This article shows how the pernicious effects of perturbations (i.e., habitat loss or hunting pressure) on ecosystems could not be immediate, producing extinction delays. These theoretical results suggest the possibility that some ecosystems could be currently trapped into the (extinction) ghost of their stable past

Butterfly-parasitoid-hostplant interactions in Western Palaearctic Hesperiidae: a DNA barcoding reference library

The study of ecological interactions between plants, phytophagous insects and their natural enemies is an essential but challenging component for understanding ecosystem dynamics. Molecular methods such as DNA barcoding can help elucidate these interactions. In this study, we employed DNA barcoding to establish hostplant and parasitoid interactions with hesperiid butterflies, using a complete reference library for Hesperiidae of continental Europe and north-western Africa (53 species, 100% of those recorded) based on 2934 sequences from 38 countries. A total of 233 hostplant and parasitoid interactions are presented, some recovered by DNA barcoding larval remains or parasitoid cocoons. Combining DNA barcode results with other lines of evidence allowed 94% species-level identification for Hesperiidae, but success was lower for parasitoids, in part due to unresolved taxonomy. Potential cases of cryptic diversity, both in Hesperiidae and Microgastrinae, are discussed. We briefly analyse the resulting interaction networks. Future DNA barcoding initiatives in this region should focus attention on north-western Africa and on parasitoids, because in these cases barcode reference libraries and taxonomy are less well developed.Support for this research was provided by the Spanish National Research Council (CSIC) with a JAE-Intro fellowship for the introduction to research to ETD (reference numbers JAEINT_20_00248 and JAEINT20_EX_0638) and by projects PID2019-107078GB-I00/MCIN/AEI/10.13039/501100011033 and 2017-SGR-991 (Generalitat de Catalunya) to RV, and PID2020-117739GA-I00/MCIN/AEI/10.13039/501100011033 to GT. We thank the Rachadaphiseksomphot Fund, Graduate School, Chulalongkorn University, for the award of a Senior Postdoctoral Fellowship to DLJQ. Further support for this research was provided by the Academy of Finland (Academy Research Fellow, decision no. 328895) to VD. PDNH acknowledges support from Genome Canada through Ontario Genomics. BV has been funded by the CERCA Programme of the Generalitat de Catalunya and by the Grant RYC-22243-2017, whose PI is Josep Sardanyés. SV was supported by the Spanish Ministry of Economy and Competitiveness, grant PID2020-117822GB-I00 MINEICO/AEI/ FEDER and the European Union.INTRODUCTION MATERIAL AND METHODS RESULTS DISCUSSION CONCLUSION SUPPORTING INFORMATION ACKNOWLEDGEMENTS DATA AVAILABILITY REFERENCES Supplementary dat

Terraforming Earth's ecosystems : engineering ecosystems to avoid anthropogenic tipping points

The idea of Terraformation comes from the science fiction literature, where humans have the capability of changing a non-habitable planet to an Earth-like one. Nowadays, Nature is changing rapidly, the poles are melting, oceans biodiversity is vanishing due to plastic pollution, and the deserts are advancing at an unstoppable rhythm. This thesis is a first step towards the exploration of new strategies that could serve to change this pernicious tendencies jeopardising ecosystems. We suggest it may not only be possible by adding new species (alien species), but also engineering autochthonous microbial species that are already adapted to the environment. Such engineering may improve their functions and capabilities allowing them to recover the (host) ecosystem upon their re-introduction. These new functionalities should make the microbes be able to induce a bottom-up change in the ecosystem: from the micro-scale (microenvironment) to the macro-scale (even changing the composition of species in the entire the ecosystem). To make this possible, the so-called Terraformation strategy needs to fuse many different fields of knowledge. The focus of this thesis relies on studying the outcome of the interactions between species and their environment (Ecology), on making the desired modifications by means of genetic engineering of the wild-type species (Synthetic Biology), and on monitoring the evaluation of the current ecosystems’ states, testing the possible changes, and predicting the future development of possible interventions (Dynamical Systems). In order to do so, in this thesis, we have gathered the tools provided by these different fields of knowledge. The methodology is based on loops between observation, designing, and prediction. For example, if there is a lack of humidity in semiarid ecosystems, we then propose to engineer e.g. Nostoc sp. to enhace its capability to produce extracellular matrix (increasing water retention). With this framework, we perform a model to understand the different possible dynamics, by means of dynamical equations to evaluate e.g. when a synthetic strain will remain in the ecosystem and the effects it will produce. We have also studied spatial models to predict their ability to modify the spatial organization of vegetation. Transient dynamics depend on the kind of transition underlying the occurring tipping point. For this reason, we have studied different systems: vegetation dynamics with facilitation (typical from drylands), a cooperator-parasite system, and a trophic chain model where different human interventions can be tested (i.e. hunting, deforestation, soil degradation, habitat destruction). All of these systems are shown to promote different types of transitions (i.e. smooth and catastrophic transitions). Each transition has its own dynamical fingerprint and thus knowing them can help monitoring and anticipating these transitions even before they happen, taking advantage of the so-called early warning signals. In this travel, we have found that transients can be an important phenomena in the current changing world. The ecosystems that we observe can be trapped into a seemingly stable regime, but be indeed in an unstable situation driving to a future sudden collapse (Fig 1) For this reason, we need to investigate novel intervention methods able to sustain the current ecosystems, for instance: Terraformation

Terraforming our planet: an overview

Trabajo presentado en el Second IBE PhD Symposium, celebrado online el 4 y 5 de febrero de 2021.Planet Earth is currently under multiple threats because of human activity. As result of the industrial revolution, ecosystems have been dramatically altered. Released CO2 is changing the global climate by disrupting temperature regulation, oceans are acidified and polluted by plastic, and many species have become extinct because of unregulated habitat destruction (i.e. deforestation). All these external perturbations are pushing ecosystems towards their limits, so-called tipping points. Such tipping points mark critical thresholds, and once they are crossed, whole ecosystems will undergo dramatic changes in their configuration (often towards a more degraded state). A particular case where this is already happening, is semiarid ecosystems. These natural environments constitute 40% of lands and any increasing temperature will cause more aridity. This in turn, will drastically reduce the vegetated landscape, and turning them into deserts. These environmental changes promote social unrest, i.e., major migrations and wars. To improve this global situation, many interventions have being proposed, e.g. , massive replantation’s or artificial dunes fixations. Here, we propose to engineer existing microbes to promote (self-)restoration of their habitats. Theoretical results suggest that using synthetic biology to enhance microbe’s functionalities could change the ecosystem’s resilience, or even revert the ecosystem to a healthier state. By studying the general limits of ecosystem dynamics, we have found that the dynamics at the tipping point depend on the type of perturbation and the existing community structure. For instance, vegetation in semiarid ecosystems could persist at high temperatures, but eventually it will rapidly become extinct, and even without further increases in temperature. This suggests the astonishing hypothesis that Earth ecosystems could be living in the ghost of their past. Ecosystems would have crossed the threshold, already. Can we save them?Peer reviewe

Bacteriophage-based synthetic biology

Treball de fi de grau en BiomèdicaTutor: Javier MaciàThe biology is complex and there is a sort of organisms that interacts worldwide. In that big system, there are the viruses, organisms that are not “alive” while they are out of the host organism. When viruses enter inside the host cell, immediately start to use their own molecular machinery in combination with the host one, in order to produce the molecules that are encoded in their genes. The first interactions between the host (inner medium, cell cycle state, etc.), and the viruses affects to behaviour will develop the virus. The behaviours are: produce copies of the viruses (lytic state) or be inserted to the host genome and be silenced until dangers for the virus became (lysogenic state). The aim of this project is to develop new applications that allow controlling -phage virus (bacteriophage) in several scenarios. The control was reached with synthetic genetic construct that interacts with the wild type genome of the virus in order to control the transition between the lysogenic and lytic states. This study was a computational approach where we use the simple model from Hasty [1] that describes CI-CRO genetic circuit, responsible of the virus bistability, and we add in this system the parts that describes our synthetic circuits. Using this approaches we have finally obtained circuits that make the bacteria immune to the -phage virus infection, lyses the cells using an external effector and finally a population control of infected cells via coupling Quorum sensing [2] with the regulation of the viral genome. For all these systems we have agent-based simulations using Netlogo. These simulations and the simplicity of the synthetic circuits give us good perspectives in order to be implemented in the wet-lab

Ecological firewalls for synthetic biology

It has been recently suggested that engineered microbial strains could be used to protect ecosystems from undesirable tipping points and biodiversity loss. A major concern in this context is the potential unintended consequences, which are usually addressed in terms of designed genetic constructs aimed at controlling overproliferation. Here we present and discuss an alternative view grounded in the nonlinear attractor dynamics of some ecological network motifs. These ecological firewalls are designed to perform novel functionalities (such as plastic removal) while containment is achieved within the resident community. That could help provide a self-regulating biocontainment. In this way, engineered organisms have a limited spread while—when required—preventing their extinction. The basic synthetic designs and their dynamical behavior are presented, each one inspired in a given ecological class of interaction. Their possible applications are discussed and the broader connection with invasion ecology outlined.B.V. and R.S. have been funded by the PR01018-EC-H2020-FET-Open MADONNA project. R.S. thanks the FIS2015-67616-P grant, and the support of Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya. B.V. has been also funded by grant RYC-2017-22243