Modeling and simulation of bacterial biofilms

The present thesis focus its efforts on developing a mathematical and experimental modelization of bacterial biofilms: bacterial colonies embedded into a polysaccharid matrix with a high resistance against removal processes, which result in a recurrent source of problems in other disciplines (medicine, engineering, etc). The behaviour of these organisms is highly dependant of the physical system in which they are present. So different case studies are faced here to show their complexity. First the dynamics of biofilms in straight ducts is studied. Experiments are performed to obtain statistics about spreading patterns, and a hybrid model (combining a discrete approach for bacterial population with stochastical behaviour rules and a continuum description of outer fields ruling those probabilities) is presented to simulate the biofilm dynamics, obtaining a successfully prediction of the different patterns observed in real experiments (at layers, ripples, streamers, mounds). This part is completed by providing an alternative continuum description of the biofilm dynamics (by deducing a lubrication equation) and extending the scope of the model to the formation of biofilm streamers inside a corner flow, where biomass adhesion mechanism become relevant. Streamers cross the channel joining both corners as observed experimentally. Additionally this thesis also includes a description of more complex dynamics observed in biofilms. An experimental description of biofilm dynamics under pulsatile flows at low Reynolds numbers show spiral patterns not reported yet, supported by a theoretical mechanism of formation based on the competence between flow dynamics and nutrient gradients. Quorum Sensing and differentiation mechanisms are also incorporated in a hybrid model to describe other kind of biofilms developed onto an agar-air interface, allowing similar geometries and cell distributions as in experiments reported previously. ---------------------------------------------------------------------------------------------------------------------------------------En esta tesis se aborda la modelización de biopelículas bacterianas, es de cir, agregados bacterianos adheridos a superficies y envueltos en una matriz polimérica que ellos mismos producen. Estos organismos son extremada mente resistentes a agresiones de todo tipo, como antibióticos o agentes químicos, lo que les confiere una gran relevancia a nivel hospitalario, indus trial o medioambiental. Su estudio se muestra especialmente complejo debido a que biopelículas formadas en distintas condiciones ambientales poseen dis tinta estructura, ya que involucran distintos comportamientos bacterianos. Inicialmente consideramos biofilms en fl ujos. Tras un estudio estadístico de su crecimiento en canales rectos, proponemos un modelo híbrido que de scribe las células como entidades que viven en una red y desarrollan actividades con una cierta probabilidad, determinada por campos de concentración continuos. Simulaciones del modelo generan estructuras similares a las ob servadas experimentalmente: ondulaciones, filamentos, championes, y per miten determinar la in fluencia de distintos parámetros en la organización del biofilm. Estudiamos la posibilidad de describir estas estructuras con modelos continuos. A continuación consideramos la in fluencia de la geometría de los canales en la forma del biofilm. Adaptamos el modelo híbrido anterior incluyendo mecanismos de adhesión y el efecto del fl ujo. Obtenemos filamentos que cruzan la corriente uniendo esquinas, similares a los observados experimen talmente. Al introducir un fl ujo pulsante, los filamentos se convierten en hilos que se enroscan en espiral. Documentamos este hecho experimentalmente y proponemos una explicación cualitativa como un balance de mecanismos de crecimiento y desplazamiento por el fluido. En los biofilms que crecen sobre superficies en contacto con el aire se activan mecanismos de diferenciación que determinan su forma. Incorporamos al modelo híbrido comportamientos de diferenciación celular por producción en cascada de autoinductores

Design and Characterisation of a Novel Artificial Life System Incorporating Hierarchical Selection

In this thesis, a minimal artificial chemistry system is presented, which is inspired by the RNA World hypothesis and is loosely based on Holland's Learning Classier Systems. The Molecular Classier System (MCS) takes a bottom-up, individual-based approach to building artificial bio-chemical networks. The MCS has been developed to demonstrate the effects of hierarchical selection. Hierarchical selection appears to have been critical for the evolution of complexity in life as we know it yet, to date, no computational artificial life system has investigated the viability of using hierarchical selection as a mechanism for achieving qualitatively similar results. Hierarchy in MCS is enforced by constraining artificial molecules, which are modeled as individuals, to exist within externally provided containers - protocells. This research is focused on the period of time surrounding the conjectured first Major Transition - from individual replicating molecules to populations of molecules existing within cells. Protocells can be thought of as simplified versions of contemporary biological cells. Molecular replication within these protocells causes them to grow until they undergo a process of binary fission. Darwinian selection is continuously and independently applied at both the molecular level and the protocell level. Experimental results are presented which display the phenomenon of selectional stalemate where the selectional pressures are applied in opposite directions such that they meet in the middle. The work culminates with the presentation of a stable artificial protocell system which is capable of demonstrating ongoing evolution at the protocell level via hierarchical selection of molecular species. Supplementary results are presented in the Appendix material as a set of experiments where selectional pressure is applied at the protocell level in a manner that indirectly favours particular artificial bio-chemical networks at the molecular level. It is shown that a molecular trait which serves no useful purpose to the molecules when they are not contained within protocells is exploited for the benefit of the collective once the molecules are constrained to live together. It is further shown that through the mechanism of hierarchical selection, the second-order effects of this molecular trait can be used by evolution to distinguish between protocells which contain desirable networks, and those that do not. A treatment of the computational potential of such a mechanism is presented with special attention given to the idea that such computation may indeed form the basis for the later evolution of the complicated Cell Signaling Pathways that are exhibited by modern cells

Complexity, Emergent Systems and Complex Biological Systems:\ud Complex Systems Theory and Biodynamics. [Edited book by I.C. Baianu, with listed contributors (2011)]

An overview is presented of System dynamics, the study of the behaviour of complex systems, Dynamical system in mathematics Dynamic programming in computer science and control theory, Complex systems biology, Neurodynamics and Psychodynamics.\u

Particle-based computer simulations of biological reaction-diffusion systems

As the life sciences become more quantitative, particle-based simulation tools can be used to model the complex spatiotemporal dynamics of biological systems with single particle resolution. In particular, they naturally account for the stochastic nature of molecular reactions. Here I apply this approach to three different biological systems that are intrinsically stochastic. As an example for cellular information processing, we investigate the receptor dynamics of the interferon type I system and show that asymmetric dimerization reactions between signaling receptors in the plasma membrane enable cells to discriminate between different ligands. Using an information theoretic framework, we show why the binding asymmetry enables this system to become robust against ligand concentration fluctuations. As an example for structure formation, we analyze the role of stochasticity and geometrical confinement for the Min oscillations that bacteria use to determine their middle. We predict mode selection as a function of geometry in excellent agreement with recent experiments and quantify the stochastic switching of oscillation modes leading to multistable oscillation patterns. As an ex- ample for self-assembly, we use a multiparticle collision dynamics (MPCD) approach to address how shear flow modulates the assembly of rings and capsids. We find that an intermediate level of shear flow can help to suppress the emergence of malformed structures. Together, these projects demonstrate the power and wide applicability of particle-based computer simulations of biological reaction-diffusion systems

V Jornadas de Investigación de la Facultad de Ciencia y Tecnología. 2016

171 p.I. Abstracts. Ahozko komunikazioak / Comunicaciones orales: 1. Biozientziak: Alderdi Molekularrak / Biociencias: Aspectos moleculares. 2. Biozientziak: Ingurune Alderdiak / Biociencias: Aspectos Ambientales. 3. Fisika eta Ingenieritza Elektronika / Física e Ingeniería Electrónica. 4. Geología / Geología. 5. Matematika / Matemáticas. 6. Kimika / Química. 7. Ingenieritza Kimikoa eta Kimika / Ingeniería Química y Química. II. Abstracts. Idatzizko Komunikazioak (Posterrak) / Comunicaciones escritas (Pósters): 1. Biozientziak / Biociencias. 2. Fisika eta Ingenieritza Elektronika / Física e Ingeniería Electrónica. 3. Geologia / Geologia. 4. Matematika / Matemáticas. 5. Kimika / Química. 6. Ingenieritza Kimikoa / Ingeniería Química

Engineering humans : cultural history of the science and technology of human enhancement

This thesis investigates the technological imaginary of human enhancement: how it has been conceived historically and the scientific understanding that has shaped it. Human enhancement technologies have been prominent in popular culture narratives for a long time, but in the past twenty years they have moved out of science fiction to being an issue for serious discussion, in academic disciplines, political debate and the mass media.. Even so, the bioethical debate on enhancement, whether it is pharmacological means of improving cognition and morality or genetic engineering to create smarter people or other possibilities, is consistently centred on technologies that do not yet exist. The investigation is divided into three main areas: a chapter on eugenics, two chapters on cybernetics and the cyborg, and two chapters on transhumanism. All three areas of enhancement thinking have a corresponding understanding of and reference to evolutionary theory and the human as a category. Insofar as ‘enhancement’ is a vague and relative turn, the chapters show how each approach wrestles with how to formulate what is good and desirable. When this has inevitably proven difficult, the technologies themselves dictate what and how ‘enhancement’ comes about. Eugenics treats the human in terms of populations – as a species, but also in abstract categories such as nation and race. I follow the establishment of eugenics from the development of a statistical understanding of measuring human aptitude, with emphasis on the work of Francis Galton and the formulation of the regression to the mean. The following two chapters on cybernetics and the cyborg analyses how the metaphor of the body as machine has changed relative to what is meant by ‘machine’: associated with Cartesian dualism, cybernetics marked a shift in how we understand the term. Through a reading of the original formulation of the cyborg, I connect it to evolutionary adaptationism and a cybernetic ‘black box’ approach. The last two chapters look at a more recent approach to enhancement as a moral imperative, transhumanism. Since some transhumanists seek to ground themselves philosophically as the inheritors to Enlightenment humanism, the concept of ‘morphological freedom’ is central, representing an extension of humanistic principles of liberty brought into an age which privileges information over matter. The final chapter looks at how the privileging of information leads to a universal computational ontology, and I specifically look at the work of Ray Kurzweil, a prominent transhumanist, and how the computationalist narrative creates a teleological understanding of both human worth and evolution

Modeling the Wound healing in Necrotizing Enterocolitis and Diabetic Foot Ulcer

In my thesis, I present three different models for the wound healing in Necrotizing Enterocolitis and Diabetic Foot Ulcer. (I) NEC results after an injury to the mucosal lining of the intestine, leading to translocation of bacteria and endotoxin. Intestinal mucosal defects are repaired by the process of intestinal restitution, during which enterocytes migrate from healthy areas to sites of injury. To model the migration of enterocytes, first we formulate a one-dimensional mathematical model based on the assumption of elastic deformation of the cell layer. Then we extend the model into a two-dimension space and the resulting moving boundary problem is solved by using modified Finite Element Method. (II) Diabetic foot ulcers (DFU) are caused by both vascular and neurologic complications of diabetes, in combination with persistent opportunistic infections and deficient wound healing. We develop an Agent-based computational model to simulate its inflammation and the resolution of the inflammatory response in its wound healing process