Arquitecturas de comunicaciones para la computacióon algorítmica en poblaciones de bacterias multi-cepa

Esta Tesis establece su desarrollo en el área interdisciplinar de la biología sintética y, más concretamente, la computación con bacterias. La unión entre la biología y las ciencias de la computación tiene su raíz a mediados del siglo XX, siendo la biología una importante fuente de inspiración para desarrollar diferentes paradigmas de cómputo en analogía directa a los seres vivos. Sin embargo, no ha sido hasta finales del mismo siglo y principios del XXI cuando el fujo de inspiración cambió de rumbo y se empezaron a construir dispositivos moleculares que actuaran como rudimentarios computadores desempeñando tareas de cálculo lógico definidas. La suma de otra disciplina, la ingeniería, ayuda a abordar el diseño de estos biosistemas como una tarea formalizada de conguración de componentes. Al observar y entender una bacteria como un sistema cuya maquinaria está formada por un conjunto de piezas funcionales diferentes, surge el objetivo de alterar los mecanismos naturales de las bacterias con el fin de construir sistemas vivos con funcionalidades no naturales. Los algoritmos aquí especificados están diseñados para llevarse a cabo en comunidades de bacterias formadas por más de una cepa, para lo cual la presente Tesis propone arquitecturas de comunicaciones diversas que ayuden a la sincronización necesaria entre bacterias distintas, basándose para ello en las capacidades y mecanismos de comunicación que las bacterias muestran en estado natural, como son la conjugación bacteriana y el quorum sensing. Esta Tesis propone la modificación y manipulación de estos mecanismos para conseguir computaciones con rudimentarios sistemas de toma de decisiones y que, en un futuro, puedan servir al desarrollo de aplicaciones en campos cientícos tan diversos como la medicina o la ecología. Entre los ejemplos de cóomputo a los que se someten las nuevas arquitecturas diseñadas caben destacar problemas complejos (TSP, SAT) y un oscilador poblacional en el que una comunidad heterogénea de bacterias muestra oscilación única. Es importante enfatizar que uno de los principales objetivos de la Tesis es la validación, tanto biológica (conocimiento experto) como computacional (simulación) de los modelos diseñados. Ya que la Tesis tiene carácter eminentemente teórico, se lleva a cabo un fuerte proceso de validación que asegure en un porcentaje muy alto el éxito de la -futura- experimentación en laboratorio con estos diseños

High-Performance Biocomputing in Synthetic Biology–Integrated Transcriptional and Metabolic Circuits

Biocomputing uses molecular biology parts as the hardware to implement computational devices. By following pre-defined rules, often hard-coded into biological systems, these devices are able to process inputs and return outputs—thus computing information. Key to the success of any biocomputing endeavor is the availability of a wealth of molecular tools and biological motifs from which functional devices can be assembled. Synthetic biology is a fabulous playground for such purpose, offering numerous genetic parts that allow for the rational engineering of genetic circuits that mimic the behavior of electronic functions, such as logic gates. A grand challenge, as far as biocomputing is concerned, is to expand the molecular hardware available beyond the realm of genetic parts by tapping into the host metabolism. This objective requires the formalization of the interplay of genetic constructs with the rest of the cellular machinery. Furthermore, the field of metabolic engineering has had little intersection with biocomputing thus far, which has led to a lack of definition of metabolic dynamics as computing basics. In this perspective article, we advocate the conceptualization of metabolism and its motifs as the way forward to achieve whole-cell biocomputations. The design of merged transcriptional and metabolic circuits will not only increase the amount and type of information being processed by a synthetic construct, but will also provide fundamental control mechanisms for increased reliability

Towards low-carbon conferencing : acceptance of virtual conferencing solutions and other sustainability measures in the ALIFE community

The latest report from the Intergovernmental Panel on Climate Change (IPCC) estimated that humanity has a time window of about 12 years in order to prevent anthropogenic climate change of catastrophic magnitude. Green house gas emission from air travel, which is currently rising, is possibly one of the factors that can be most readily reduced. Within this context, we advocate for the re-design of academic conferences in order to decrease their environmental footprint. Today, virtual technologies hold the promise to substitute many forms of physical interactions and increasingly make their way into conferences to reduce the number of travelling delegates. Here, we present the results of a survey in which we gathered the opinion on this topic of academics worldwide. Results suggest there is ample room for challenging the (dangerous) business-as-usual inertia of scientific lifestyle

Multicellular Computing Using Conjugation for Wiring

Recent efforts in synthetic biology have focussed on the implementation of logical functions within living cells. One aim is to facilitate both internal ‘‘re-programming’’ and external control of cells, with potential applications in a wide range of domains. However, fundamental limitations on the degree to which single cells may be re-engineered have led to a growth of interest in multicellular systems, in which a ‘‘computation’’ is distributed over a number of different cell types, in a manner analogous to modern computer networks. Within this model, individual cell type perform specific sub-tasks, the results of which are then communicated to other cell types for further processing. The manner in which outputs are communicated is therefore of great significance to the overall success of such a scheme. Previous experiments in distributed cellular computation have used global communication schemes, such as quorum sensing (QS), to implement the ‘‘wiring’’ between cell types. While useful, this method lacks specificity, and limits the amount of information that may be transferred at any one time. We propose an alternative scheme, based on specific cell-cell conjugation. This mechanism allows for the direct transfer of genetic information between bacteria, via circular DNA strands known as plasmids. We design a multicellular population that is able to compute, in a distributed fashion, a Boolean XOR function. Through this, we describe a general scheme for distributed logic that works by mixing different strains in a single population; this constitutes an important advantage of our novel approach. Importantly, the amount of genetic information exchanged through conjugation is significantly higher than the amount possible through QS-based communication. We provide full computational modelling and simulation results, using deterministic, stochastic and spatially-explicit methods. These simulations explore the behaviour of one possible conjugation-wired cellular computing system under different conditions, and provide baseline information for future laboratory implementations

Cellular Computing and Synthetic Biology

Synthetic biology is an emerging, rapidly growing research field in which engineering principles are applied to natural, living systems. A major goal of synthetic biology is to harness the inherent “biological nanotechnology” of living cells for a number of applications, including computation, production, and diagnosis. In its infancy, synthetic biology was mainly concerned with the construction of small-scale, proof-of-principle computational devices (cellular computing), along the lines of simple logic gates and circuits, but the state-of-the-art now uses multicellular complexes and engineered cell-cell communication. From its practical origins around the turn of the century, the field has grown into a global scientific market predicted to be worth tens of billions of dollars by 2020. Anticipated applications include tissue engineering, environmental remediation, in situ disease detection and treatment, and even the development of the first fully-synthetic organism. In this chapter we review the timeline of synthetic biology, describe its alignment with unconventional computation, and, drawing on quotations from leading researchers in the field, describe its main challenges and opportunities

Continuous computation in engineered gene circuits

In this paper we consider the problem of representation and measurement in genetic circuits, and investigate how they can affect the reliability of engineered systems. We propose a design scheme, based on the notion of continuous computation, which addresses these issues. We illustrate the methodology by showing how a concept from computer architecture (namely, branch prediction) may be implemented in vivo, using a distributed approach. Simulation results confirm the in-principle feasibility of our method, and offer valuable insights into its future laboratory validation

Physical forces shape group identity of swimming Pseudomonas putida cells

The often striking macroscopic patterns developed by motile bacterial populations on agar plates are a consequence of the environmental conditions where the cells grow and spread. Parameters such as medium stiffness and nutrient concentration have been reported to alter cell swimming behavior, while mutual interactions among populations shape collective patterns. One commonly observed occurrence is the mutual inhibition of clonal bacteria when moving towards each other, which results in a distinct halt at a finite distance on the agar matrix before having direct contact. The dynamics behind this phenomenon (i.e. intolerance to mix in time and space with otherwise identical others) has been traditionally explained in terms of cell-to-cell competition/cooperation regarding nutrient availability. In this work, the same scenario has been revisited from an alternative perspective: the effect of the physical mechanics that frame the process, in particular the consequences of collisions between moving bacteria and the semi-solid matrix of the swimming medium. To this end we set up a simple experimental system in which the swimming patterns of Pseudomonas putida were tested with different geometries and agar concentrations. A computational analysis framework that highlights cell-to-medium interactions was developed to fit experimental observations. Simulated outputs suggested that the medium is compressed in the direction of the bacterial front motion. This phenomenon generates what was termed a compression wave that goes through the medium preceding the swimming population and that determines the visible high-level pattern. Taken together, the data suggested that the mechanical effects of the bacteria moving through the medium created a factual barrier that impedes to merge with neighboring cells swimming from a different site. The resulting divide between otherwise clonal bacteria is thus brought about by physical forces –not genetic or metabolic programs

Time evolution of NOR_1 according to a specific input profile.

<p>Logic case 1-1 is induced during the intervals [0…200] min and [400…500] min (A and B = 500 molecules -constant entry- during the interval). The case 0-0 domains during the rest of the 600 min. According to that profile we observe the deterministic oscillation of FimE/FimB (top graph) as well as the oscillation between the two possible plasmids in NOR_1 ( and ). The latter relation is shown deterministically (middle graph) and stochastically (bottom graph) (copy number = 5). Delays in response are due to input degradation times.</p