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Research paper thumbnail of Synthetic Ecosystems: From the Test Tube to the Biosphere

Research paper thumbnail of Mapa del microbioma d'una ciutat: el Barcelona MicroBioMap

Zenodo (CERN European Organization for Nuclear Research), Apr 29, 2022

Research paper thumbnail of 14+ MILLION TOP 1% MOST CITED SCIENTIST 12.2% AUTHORS AND EDITORS FROM TOP 500 UNIVERSITIES Chapter from the book Data Mining in Medical and Biological Research Topological Analysis of Cellular Networks

a given condition, such as two metabolites participating in the same reaction in a metabolic netw... more a given condition, such as two metabolites participating in the same reaction in a metabolic network. The graph definition does not imply that all nodes must be connected in a single component. A connected component in a graph is formed by a set of elements so that there is at least one path connecting any two of them. Graphs are undirected when the interaction between nodes is mutual and equal, as in the protein maps. On the contrary, the web is directed when the connection indicates that one element affect to the other but not the opposite. As we will see, this is the case of gene regulatory networks (Shen-Orr et al. 2002) and signal transduction pathways (Ma'ayan et al. 2005). Additionally, graphs can also be weighted when links have values according to a certain property. This is the case for gene regulatory networks, where weights indicate the strength and direction of regulatory interactions. Although graphs are usually represented as a plot of nodes and connecting edges, they can also be defined by means of the so-called adjacency matrix, i.e., an array A of NxN elements a ij , where a ij =1 if v i links to v j and zero otherwise. A is symmetric for undirected graphs, but not for the directed ones. For weighted nets a matrix W can be introduced, where w ij indicates the strength and type of the link. The network can also be described using a list of pairs of connected nodes (edge-list), which has some computational advantages. Figure 1 summarizes the different ways of representing a graph.

Research paper thumbnail of Simulació d’un sistema natural deprocessament distribuït de la informació: elPhysarum Polycephalum

Research paper thumbnail of Synthetic Lateral Inhibition in Periodic Pattern Forming Microbial Colonies

Research paper thumbnail of Electrochemical Characterisation of Bio-Bottle-Voltaic (BBV) Systems Operated with Algae and Built with Recycled Materials

Biology, Jan 17, 2018

Photobioelectrochemical systems are an emerging possibility for renewable energy. By exploiting p... more Photobioelectrochemical systems are an emerging possibility for renewable energy. By exploiting photosynthesis, they transform the energy of light into electricity. This study evaluates a simple, scalable bioelectrochemical system built from recycled plastic bottles, equipped with an anode made from recycled aluminum, and operated with the green alga . We tested whether such a system, referred to as a bio-bottle-voltaic (BBV) device, could operate outdoors for a prolonged time period of 35 days. Electrochemical characterisation was conducted by measuring the drop in potential between the anode and the cathode, and this value was used to calculate the rate of charge accumulation. The BBV systems were initially able to deliver ~500 mC·bottle·day, which increased throughout the experimental run to a maximum of ~2000 mC·bottle·day. The electrical output was consistently and significantly higher than that of the abiotic BBV system operated without algal cells ...

Research paper thumbnail of Simulació d’un sistema natural de/nprocessament distribuït de la informació: el/nPhysarum Polycephalum

Research paper thumbnail of Engineering self-organized criticality in living cells

Complex dynamical fluctuations, from molecular noise within cells, collective intelligence, brain... more Complex dynamical fluctuations, from molecular noise within cells, collective intelligence, brain dynamics or computer traffic have been shown to display noisy behaviour consistent with a critical state between order and disorder. Living close to the critical point can have a number of adaptive advantages and it has been conjectured that evolution could select (and even tend to) these critical states. One way of approaching such state is by means of so called self-organized criticality (SOC) where the system poises itself close to the critical point. Is this the case of living cells? It is difficult to test this idea given the enormous dimensionality associated with gene and metabolic webs. In this paper we present an alternative approach: to engineer synthetic gene networks displaying SOC behaviour. This is achieved by exploiting the presence of a saturation (congestion) phenomenon of the ClpXP protein degradation machinery in E. coli cells. Using a feedback design that detects and...

Research paper thumbnail of Synthetic Biology for Terraformation: Lessons from Mars, Earth and the Microbiome

What is the potential for synthetic biology as a way of engineering, on a large scale, complex ec... more What is the potential for synthetic biology as a way of engineering, on a large scale, complex ecosystems? Can it be used to change endangered ecological communities and rescue them to prevent their collapse? What are the best strategies for such ecological engineering paths to succeed? Is it possible to create stable, diverse synthetic ecosystems capable of persisting in closed environments? Can synthetic communities be created to thrive on planets different from ours? These and other questions pervade major future developments within synthetic biology. The goal of engineering ecosystems is plagued with all kinds of technological, scientific and ethic problems. In this paper we consider the requirements for Terraformation, i. e. for changing a given environment to make it hospitable to some given class of life forms. Although the standard use of this term involved strategies for planetary terraformation, it has been recently suggested that this approach could be applied to a very d...

Research paper thumbnail of A Synthetic Multicellular Memory Device

ACS Synthetic Biology, 2016

Research paper thumbnail of A morphospace for synthetic organs and organoids: the possible and the actual

Integrative biology : quantitative biosciences from nano to macro, 2016

Efforts in evolutionary developmental biology have shed light on how organs are developed and why... more Efforts in evolutionary developmental biology have shed light on how organs are developed and why evolution has selected some structures instead of others. These advances in the understanding of organogenesis along with the most recent techniques of organotypic cultures, tissue bioprinting and synthetic biology provide the tools to hack the physical and genetic constraints in organ development, thus opening new avenues for research in the form of completely designed or merely altered settings. Here we propose a unifying framework that connects the concept of morphospace (i.e. the space of possible structures) with synthetic biology and tissue engineering. We aim for a synthesis that incorporates our understanding of both evolutionary and architectural constraints and can be used as a guide for exploring alternative design principles to build artificial organs and organoids. We present a three-dimensional morphospace incorporating three key features associated to organ and organoid c...

Research paper thumbnail of Synthetic collective intelligence

Biosystems, 2016

Intelligent systems have emerged in our biosphere in different contexts and achieving different l... more Intelligent systems have emerged in our biosphere in different contexts and achieving different levels of complexity. The requirement of communication in a social context has been in all cases a determinant. The human brain, probably co-evolving with language, is an exceedingly successful example. Similarly, social insects complex collective decisions emerge from information exchanges between many agents. The difference is that such processing is obtained out of a limited individual cognitive power. Computational models and embodied versions using non-living systems, particularly involving robot swarms, have been used to explore the potentiality of collective intelligence. Here we suggest a novel approach to the problem grounded in the genetic engineering of unicellular systems, which can be modified in order to interact, store memories or adapt to external stimuli in collective ways. What we label as Synthetic Swarm Intelligence defines a parallel approach to the evolution of computation and swarm intelligence and allows to explore potential embodied scenarios for decision making at the microscale. Here, we consider several relevant examples of collective intelligence and their synthetic organism counterparts.

Research paper thumbnail of Computational implementation of a tunable multicellular memory circuit for engineered eukaryotic consortia

Frontiers in Physiology, 2015

Cells are complex machines capable of processing information by means of an entangled network of ... more Cells are complex machines capable of processing information by means of an entangled network of molecular interactions. A crucial component of these decision-making systems is the presence of memory and this is also a specially relevant target of engineered synthetic systems. A classic example of memory devices is a 1-bit memory element known as the flip-flop. Such system can be in principle designed using a single-cell implementation, but a direct mapping between standard circuit design and a living circuit can be cumbersome. Here we present a novel computational implementation of a 1-bit memory device using a reliable multicellular design able to behave as a set-reset flip-flop that could be implemented in yeast cells. The dynamics of the proposed synthetic circuit is investigated with a mathematical model using biologically-meaningful parameters. The circuit is shown to behave as a flip-flop in a wide range of parameter values. The repression strength for the NOT logics is shown to be crucial to obtain a good flip-flop signal. Our model also shows that the circuit can be externally tuned to achieve different memory states and dynamics, such as persistent and transient memory. We have characterized the parameter domains for robust memory storage and retrieval as well as the corresponding time response dynamics.

Research paper thumbnail of Hog1 bypasses stress-mediated down-regulation of transcription by RNA polymerase II redistribution and chromatin remodeling

Genome Biology, 2012

Background: Cells are subjected to dramatic changes of gene expression upon environmental changes... more Background: Cells are subjected to dramatic changes of gene expression upon environmental changes. Stress causes a general down-regulation of gene expression together with the induction of a set of stress-responsive genes. The p38-related stress-activated protein kinase Hog1 is an important regulator of transcription upon osmostress in yeast. Results: Genome-wide localization studies of RNA polymerase II (RNA Pol II) and Hog1 showed that stress induced major changes in RNA Pol II localization, with a shift toward stress-responsive genes relative to housekeeping genes. RNA Pol II relocalization required Hog1, which was also localized to stress-responsive loci. In addition to RNA Pol II-bound genes, Hog1 also localized to RNA polymerase III-bound genes, pointing to a wider role for Hog1 in transcriptional control than initially expected. Interestingly, an increasing association of Hog1 with stressresponsive genes was strongly correlated with chromatin remodeling and increased gene expression. Remarkably, MNase-Seq analysis showed that although chromatin structure was not significantly altered at a genome-wide level in response to stress, there was pronounced chromatin remodeling for those genes that displayed Hog1 association. Conclusion: Hog1 serves to bypass the general down-regulation of gene expression that occurs in response to osmostress, and does so both by targeting RNA Pol II machinery and by inducing chromatin remodeling at stressresponsive loci.

Research paper thumbnail of Topological Analysis of Cellular Networks

Data Mining in Medical and Biological Research, 2008

Research paper thumbnail of Implementation of Complex Biological Logic Circuits Using Spatially Distributed Multicellular Consortia

PLOS Computational Biology, 2016

Engineered synthetic biological devices have been designed to perform a variety of functions from... more Engineered synthetic biological devices have been designed to perform a variety of functions from sensing molecules and bioremediation to energy production and biomedicine. Notwithstanding, a major limitation of in vivo circuit implementation is the constraint associated to the use of standard methodologies for circuit design. Thus, future success of these devices depends on obtaining circuits with scalable complexity and reusable parts. Here we show how to build complex computational devices using multicellular consortia and space as key computational elements. This spatial modular design grants scalability since its general architecture is independent of the circuit's complexity, minimizes wiring requirements and allows component reusability with minimal genetic engineering. The potential use of this approach is demonstrated by implementation of complex logical functions with up to six inputs, thus demonstrating the scalability and flexibility of this method. The potential implications of our results are outlined.

Research paper thumbnail of Ecografías para examinar microorganismos intestinales

Research paper thumbnail of DIYbio. Els biohackers: una nova manera de fer créixer la biotecnologia

Research paper thumbnail of Distributed biological computation with multicellular engineered networks

Nature, 2010

For synthetic biologists' creativity to be unleashed, basic circuits must become truly inter... more For synthetic biologists' creativity to be unleashed, basic circuits must become truly interchangeable, that is, modular and scalable. This study, one of two linked papers, has harnessed yeast pheromone communication to achieve complex computation through ...

Research paper thumbnail of Human synthetic lethal inference as potential anti-cancer target gene detection

BMC Systems Biology, Dec 16, 2009

Background Two genes are called synthetic lethal (SL) if mutation of either alone is not lethal, ... more Background Two genes are called synthetic lethal (SL) if mutation of either alone is not lethal, but mutation of both leads to death or a significant decrease in organism's fitness. The detection of SL gene pairs constitutes a promising alternative for anti-cancer therapy. As cancer cells exhibit a large number of mutations, the identification of these mutated genes' SL partners may provide specific anti-cancer drug candidates, with minor perturbations to the healthy cells. Since existent SL data is mainly restricted to yeast screenings, the road ...

Research paper thumbnail of Synthetic Ecosystems: From the Test Tube to the Biosphere

Research paper thumbnail of Mapa del microbioma d'una ciutat: el Barcelona MicroBioMap

Zenodo (CERN European Organization for Nuclear Research), Apr 29, 2022

Research paper thumbnail of 14+ MILLION TOP 1% MOST CITED SCIENTIST 12.2% AUTHORS AND EDITORS FROM TOP 500 UNIVERSITIES Chapter from the book Data Mining in Medical and Biological Research Topological Analysis of Cellular Networks

a given condition, such as two metabolites participating in the same reaction in a metabolic netw... more a given condition, such as two metabolites participating in the same reaction in a metabolic network. The graph definition does not imply that all nodes must be connected in a single component. A connected component in a graph is formed by a set of elements so that there is at least one path connecting any two of them. Graphs are undirected when the interaction between nodes is mutual and equal, as in the protein maps. On the contrary, the web is directed when the connection indicates that one element affect to the other but not the opposite. As we will see, this is the case of gene regulatory networks (Shen-Orr et al. 2002) and signal transduction pathways (Ma'ayan et al. 2005). Additionally, graphs can also be weighted when links have values according to a certain property. This is the case for gene regulatory networks, where weights indicate the strength and direction of regulatory interactions. Although graphs are usually represented as a plot of nodes and connecting edges, they can also be defined by means of the so-called adjacency matrix, i.e., an array A of NxN elements a ij , where a ij =1 if v i links to v j and zero otherwise. A is symmetric for undirected graphs, but not for the directed ones. For weighted nets a matrix W can be introduced, where w ij indicates the strength and type of the link. The network can also be described using a list of pairs of connected nodes (edge-list), which has some computational advantages. Figure 1 summarizes the different ways of representing a graph.

Research paper thumbnail of Simulació d’un sistema natural deprocessament distribuït de la informació: elPhysarum Polycephalum

Research paper thumbnail of Synthetic Lateral Inhibition in Periodic Pattern Forming Microbial Colonies

Research paper thumbnail of Electrochemical Characterisation of Bio-Bottle-Voltaic (BBV) Systems Operated with Algae and Built with Recycled Materials

Biology, Jan 17, 2018

Photobioelectrochemical systems are an emerging possibility for renewable energy. By exploiting p... more Photobioelectrochemical systems are an emerging possibility for renewable energy. By exploiting photosynthesis, they transform the energy of light into electricity. This study evaluates a simple, scalable bioelectrochemical system built from recycled plastic bottles, equipped with an anode made from recycled aluminum, and operated with the green alga . We tested whether such a system, referred to as a bio-bottle-voltaic (BBV) device, could operate outdoors for a prolonged time period of 35 days. Electrochemical characterisation was conducted by measuring the drop in potential between the anode and the cathode, and this value was used to calculate the rate of charge accumulation. The BBV systems were initially able to deliver ~500 mC·bottle·day, which increased throughout the experimental run to a maximum of ~2000 mC·bottle·day. The electrical output was consistently and significantly higher than that of the abiotic BBV system operated without algal cells ...

Research paper thumbnail of Simulació d’un sistema natural de/nprocessament distribuït de la informació: el/nPhysarum Polycephalum

Research paper thumbnail of Engineering self-organized criticality in living cells

Complex dynamical fluctuations, from molecular noise within cells, collective intelligence, brain... more Complex dynamical fluctuations, from molecular noise within cells, collective intelligence, brain dynamics or computer traffic have been shown to display noisy behaviour consistent with a critical state between order and disorder. Living close to the critical point can have a number of adaptive advantages and it has been conjectured that evolution could select (and even tend to) these critical states. One way of approaching such state is by means of so called self-organized criticality (SOC) where the system poises itself close to the critical point. Is this the case of living cells? It is difficult to test this idea given the enormous dimensionality associated with gene and metabolic webs. In this paper we present an alternative approach: to engineer synthetic gene networks displaying SOC behaviour. This is achieved by exploiting the presence of a saturation (congestion) phenomenon of the ClpXP protein degradation machinery in E. coli cells. Using a feedback design that detects and...

Research paper thumbnail of Synthetic Biology for Terraformation: Lessons from Mars, Earth and the Microbiome

What is the potential for synthetic biology as a way of engineering, on a large scale, complex ec... more What is the potential for synthetic biology as a way of engineering, on a large scale, complex ecosystems? Can it be used to change endangered ecological communities and rescue them to prevent their collapse? What are the best strategies for such ecological engineering paths to succeed? Is it possible to create stable, diverse synthetic ecosystems capable of persisting in closed environments? Can synthetic communities be created to thrive on planets different from ours? These and other questions pervade major future developments within synthetic biology. The goal of engineering ecosystems is plagued with all kinds of technological, scientific and ethic problems. In this paper we consider the requirements for Terraformation, i. e. for changing a given environment to make it hospitable to some given class of life forms. Although the standard use of this term involved strategies for planetary terraformation, it has been recently suggested that this approach could be applied to a very d...

Research paper thumbnail of A Synthetic Multicellular Memory Device

ACS Synthetic Biology, 2016

Research paper thumbnail of A morphospace for synthetic organs and organoids: the possible and the actual

Integrative biology : quantitative biosciences from nano to macro, 2016

Efforts in evolutionary developmental biology have shed light on how organs are developed and why... more Efforts in evolutionary developmental biology have shed light on how organs are developed and why evolution has selected some structures instead of others. These advances in the understanding of organogenesis along with the most recent techniques of organotypic cultures, tissue bioprinting and synthetic biology provide the tools to hack the physical and genetic constraints in organ development, thus opening new avenues for research in the form of completely designed or merely altered settings. Here we propose a unifying framework that connects the concept of morphospace (i.e. the space of possible structures) with synthetic biology and tissue engineering. We aim for a synthesis that incorporates our understanding of both evolutionary and architectural constraints and can be used as a guide for exploring alternative design principles to build artificial organs and organoids. We present a three-dimensional morphospace incorporating three key features associated to organ and organoid c...

Research paper thumbnail of Synthetic collective intelligence

Biosystems, 2016

Intelligent systems have emerged in our biosphere in different contexts and achieving different l... more Intelligent systems have emerged in our biosphere in different contexts and achieving different levels of complexity. The requirement of communication in a social context has been in all cases a determinant. The human brain, probably co-evolving with language, is an exceedingly successful example. Similarly, social insects complex collective decisions emerge from information exchanges between many agents. The difference is that such processing is obtained out of a limited individual cognitive power. Computational models and embodied versions using non-living systems, particularly involving robot swarms, have been used to explore the potentiality of collective intelligence. Here we suggest a novel approach to the problem grounded in the genetic engineering of unicellular systems, which can be modified in order to interact, store memories or adapt to external stimuli in collective ways. What we label as Synthetic Swarm Intelligence defines a parallel approach to the evolution of computation and swarm intelligence and allows to explore potential embodied scenarios for decision making at the microscale. Here, we consider several relevant examples of collective intelligence and their synthetic organism counterparts.

Research paper thumbnail of Computational implementation of a tunable multicellular memory circuit for engineered eukaryotic consortia

Frontiers in Physiology, 2015

Cells are complex machines capable of processing information by means of an entangled network of ... more Cells are complex machines capable of processing information by means of an entangled network of molecular interactions. A crucial component of these decision-making systems is the presence of memory and this is also a specially relevant target of engineered synthetic systems. A classic example of memory devices is a 1-bit memory element known as the flip-flop. Such system can be in principle designed using a single-cell implementation, but a direct mapping between standard circuit design and a living circuit can be cumbersome. Here we present a novel computational implementation of a 1-bit memory device using a reliable multicellular design able to behave as a set-reset flip-flop that could be implemented in yeast cells. The dynamics of the proposed synthetic circuit is investigated with a mathematical model using biologically-meaningful parameters. The circuit is shown to behave as a flip-flop in a wide range of parameter values. The repression strength for the NOT logics is shown to be crucial to obtain a good flip-flop signal. Our model also shows that the circuit can be externally tuned to achieve different memory states and dynamics, such as persistent and transient memory. We have characterized the parameter domains for robust memory storage and retrieval as well as the corresponding time response dynamics.

Research paper thumbnail of Hog1 bypasses stress-mediated down-regulation of transcription by RNA polymerase II redistribution and chromatin remodeling

Genome Biology, 2012

Background: Cells are subjected to dramatic changes of gene expression upon environmental changes... more Background: Cells are subjected to dramatic changes of gene expression upon environmental changes. Stress causes a general down-regulation of gene expression together with the induction of a set of stress-responsive genes. The p38-related stress-activated protein kinase Hog1 is an important regulator of transcription upon osmostress in yeast. Results: Genome-wide localization studies of RNA polymerase II (RNA Pol II) and Hog1 showed that stress induced major changes in RNA Pol II localization, with a shift toward stress-responsive genes relative to housekeeping genes. RNA Pol II relocalization required Hog1, which was also localized to stress-responsive loci. In addition to RNA Pol II-bound genes, Hog1 also localized to RNA polymerase III-bound genes, pointing to a wider role for Hog1 in transcriptional control than initially expected. Interestingly, an increasing association of Hog1 with stressresponsive genes was strongly correlated with chromatin remodeling and increased gene expression. Remarkably, MNase-Seq analysis showed that although chromatin structure was not significantly altered at a genome-wide level in response to stress, there was pronounced chromatin remodeling for those genes that displayed Hog1 association. Conclusion: Hog1 serves to bypass the general down-regulation of gene expression that occurs in response to osmostress, and does so both by targeting RNA Pol II machinery and by inducing chromatin remodeling at stressresponsive loci.

Research paper thumbnail of Topological Analysis of Cellular Networks

Data Mining in Medical and Biological Research, 2008

Research paper thumbnail of Implementation of Complex Biological Logic Circuits Using Spatially Distributed Multicellular Consortia

PLOS Computational Biology, 2016

Engineered synthetic biological devices have been designed to perform a variety of functions from... more Engineered synthetic biological devices have been designed to perform a variety of functions from sensing molecules and bioremediation to energy production and biomedicine. Notwithstanding, a major limitation of in vivo circuit implementation is the constraint associated to the use of standard methodologies for circuit design. Thus, future success of these devices depends on obtaining circuits with scalable complexity and reusable parts. Here we show how to build complex computational devices using multicellular consortia and space as key computational elements. This spatial modular design grants scalability since its general architecture is independent of the circuit's complexity, minimizes wiring requirements and allows component reusability with minimal genetic engineering. The potential use of this approach is demonstrated by implementation of complex logical functions with up to six inputs, thus demonstrating the scalability and flexibility of this method. The potential implications of our results are outlined.

Research paper thumbnail of Ecografías para examinar microorganismos intestinales

Research paper thumbnail of DIYbio. Els biohackers: una nova manera de fer créixer la biotecnologia

Research paper thumbnail of Distributed biological computation with multicellular engineered networks

Nature, 2010

For synthetic biologists' creativity to be unleashed, basic circuits must become truly inter... more For synthetic biologists' creativity to be unleashed, basic circuits must become truly interchangeable, that is, modular and scalable. This study, one of two linked papers, has harnessed yeast pheromone communication to achieve complex computation through ...

Research paper thumbnail of Human synthetic lethal inference as potential anti-cancer target gene detection

BMC Systems Biology, Dec 16, 2009

Background Two genes are called synthetic lethal (SL) if mutation of either alone is not lethal, ... more Background Two genes are called synthetic lethal (SL) if mutation of either alone is not lethal, but mutation of both leads to death or a significant decrease in organism's fitness. The detection of SL gene pairs constitutes a promising alternative for anti-cancer therapy. As cancer cells exhibit a large number of mutations, the identification of these mutated genes' SL partners may provide specific anti-cancer drug candidates, with minor perturbations to the healthy cells. Since existent SL data is mainly restricted to yeast screenings, the road ...