Biología 2.0: Búsqueda de los principios de computación celular a través de la Biología Sintética

Actividad integrada en el curso "Bioinformática y análisis de datos" (Coordinador: Prof. Enrique Viguera Mínguez). Máster Biotecnología AvanzadaLa biología sintética es una disciplina de nueva formación que busca la consolidación de una ingeniería partiendo de la biología molecular. En esta charla se discuten las diferencias entre esta nueva aproximación y las ya existentes como la biotecnología, biología molecular e ingeniería genética. En esta aproximación una de las primeras necesidades es la estandarización de protocolos y piezas moleculares, llamadas partes genéticas que combinándolas se busca la creación de comportamientos moleculares no triviales. En este aspecto se presenta las iniciativas tipo iGEM una competición a nivel mundial en el que se pretende fomentar este tipo de disciplina en centros universitarios. Un segundo punto importante es la aproximación matemática y de creación y utilización de modelos, intrínseca a toda ingeniería. Gracias al uso de las matemáticas y de la computación se busca un diseño racional de circuitos de génicos que realicen un comportamiento no trivial. La forma de trabajo radica en generar modelos predictivos, dejando atrás o reduciendo ¡hasta donde sea posible la aproximación tipo prueba y error. Por último en esta charla se presenta de forma muy general el potencial que esta disciplina representa y las aplicaciones y distintas expectativas del área. Ejemplos citados son creación de bio-sensores con interés biomédico, o la llamada computación celular, es decir, el uso de células para conseguir puertas lógicas, al igual que ocurre e una computación estándar.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

De la idea al negocio o ¿Cómo montar una startup biotecnológica?

En la sociedad actual es cada vez más común hablar de emprendimiento. Emprender es afrontar la incertidumbre del desarrollo de un proyecto que generalmente contiene una componente alta de innovación. Las habilidades requeridas no son, en realidad, diferentes a la que la carrera científica exige: gestión de la incertidumbre, valoración del riesgo, perseverancia y sacrificio en un entorno cambiante y competitivo. De hecho, no es casual que detrás de las startups que han acabado en empresas de éxito hayan perfiles altamente tecnológicos. Empresas actuales como Google, Tesla o personalidades como Bill Gates o Craig Venter son ejemplos de emprendimiento con base tecnológica. La presente charla busca aportar los elementos necesarios de como desde la investigación se puede llegar a ser emprendedor, ofreciendo además un testimonio en primera persona para aquellos que se plantean alternativas más allá del entorno académico.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

¿Qué es la conectómica?

The advances in neuroimaging have provided unprecedented insight about how the brain is. Beyond brain structure visualisation, a new discipline has emerged from the interaction between neuroimaging techniques and the so-called network theory. The result of this convergence is the connectomics. This article talks about what it is and how is transforming our understanding of the brain.Los avances en neuroimagen han proporcionado un marco sin precedentes sobre cómo es el cerebro. Más allá de la visualización de estructuras del cerebro, esta nueva disciplina surge de la interacción de las técnicas de neuroimagen y la llamada teoría de redes. El resultado de esta convergencia es la conectómica. En este artículo mostramos qué es y cómo está transformando la comprensión del cerebro

Análisis multinivel de los factores asociados a la educación cívica en estudiantes de secundaria

La presente investigación tuvo como propósito analizar los efectos de un conjunto de variables personales y escolares en las actitudes cívicas en una muestra de estudiantes mexicanos de educación secundaria (n=4,111). Los datos obtenidos, producto de la aplicación de la adaptación del Civic Education Study de la International Association for the Evaluation of Educational Achievement (IEA), se analizaron mediante el modelamiento multinivel, controlando los efectos del nivel socioeconómico y tipo de escuela. Los resultados muestran que el tipo de secundaria y el nivel socioeconómico explican sólo una proporción marginal de la varianza asociada con las actitudes cívicas, donde el mayor porcentaje de la varianza se explica por variables de naturaleza personal

La Biología Sintética y la comunidad DIY

In recent years, the Do-It-Yourself (DIY) culture has been making its way as a social phenomenon. This brings together various hobbies and activities, the common point of all of them is creating and manufacturing some type of product by oneself. In many ways it is synonymous with traditional crafts. However, today, making a sweater by hand or a crocheted rug with recycled material is the latest trend in underground markets. Beyond an aesthetic issue, more and more activities are incorporated under the DIY label that require a level of precision and knowledge that until now were only considered in the purely professional field. Today we are not only talking about making some booties, but about editing a book, publishing a record or design and sell a cloth bag online that is available, commentable and tweetable in and from any place. In the field of technology the scenario has evolved enormously. From the first electronics enthusiasts who patiently soldered their circuits following thick manuals, we have moved on to a personnel profile that combines electronics and programming. From this community, a whole repertoire of projects is being developed that can compete with traditional commercial initiatives. As we will see, the do-it-yourself culture has come to consider genetic manipulation as another element of this cultural movement.En los últimos años, la cultura Do-It-Yourself (DIY) o hazlo tu mismo ha ido abriéndose paso como un fenómeno social. Éste aglutina diversas aficiones y actividades, el punto en común de todas ellas es el crear y fabricar por uno mismo algún tipo de producto. En muchos aspectos es un sinónimo de las manualidades de toda la vida. Sin embargo, hacer hoy un jersey a mano o un tapete de ganchillo con material reciclado es el último grito de los mercadillos underground. Más allá de un tema estético, bajo la etiqueta de DIY se incorporan cada vez más actividades que requieren un nivel de precisión y conocimiento que hasta ahora sólo se planteaban en el ámbito puramente profesional. Hoy no solo hablamos de hacer unos patucos, sino de editar un libro, publicar un disco o diseñar y vender por Internet un bolso de tela que esté disponible, comentable y ‘tuiteable’ en y desde cualquier parte del mundo. En el ámbito de la tecnología el escenario ha evolucionado enormemente. Desde los primeros aficionados a la electrónica que soldaban pacientemente sus circuitos siguiendo gruesos manuales se ha pasado a un perfil de personal que combina electrónica y programación. Desde esta comunidad se están desarrollando todo un repertorio de proyectos que puede llegar a competir con iniciativas comerciales tradicionales. Como veremos, la cultura do-it-yourself ha llegado considerar la manipulación genética como un elemento más de este movimiento cultura

Measuring the hierarchy of feedforward networks

12 páginas, 6 figuras.In this paper we explore the concept of hierarchy as a quantifiable descriptor of ordered structures, departing from the definition of three conditions to be satisfied for a hierarchical structure: order, predictability, and pyramidal structure. According to these principles, we define a hierarchical index taking concepts from graph and information theory. This estimator allows to quantify the hierarchical character of any system susceptible to be abstracted in a feedforward causal graph, i.e., a directed acyclic graph defined in a single connected structure. Our hierarchical index is a balance between this predictability and pyramidal condition by the definition of two entropies: one attending the onward flow and the other for the backward reversion.We show how this index allows to identify hierarchical, antihierarchical, and nonhierarchical structures. Our formalism reveals that departing from the defined conditions for a hierarchical structure, feedforward trees and the inverted tree graphs emerge as the only causal structures of maximal hierarchical and antihierarchical systems respectively. Conversely, null values of the hierarchical index are attributed to a number of different configuration networks; from linear chains, due to their lack of pyramid structure, to full-connected feedforward graphs where the diversity of onward pathways is canceled by the uncertainty (lack of predictability) when going backward. Some illustrative examples are provided for the distinction among these three types of hierarchical causal graphs.This work was supported by the EU 6th framework project ComplexDis (NEST-043241, CRC and JG), the UTE project CIMA (JG), Fundación Marcelino Botín (CRC), the James McDonnell Foundation (BCM and RVS) and the Santa Fe Institute (RVS)

Human synthetic lethal inference as potential anti-cancer target gene detection

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 towards human SL candidates is limited to inference methods. Results: In the present work, we use phylogenetic analysis and database manipulation (BioGRID for interactions, Ensembl and NCBI for homology, Gene Ontology for GO attributes) in order to reconstruct the phylogenetically-inferred SL gene network for human. In addition, available data on cancer mutated genes (COSMIC and Cancer Gene Census databases) as well as on existent approved drugs (DrugBank database) supports our selection of cancer-therapy candidates./nConclusions: Our work provides a complementary alternative to the current methods for drug discovering and gene target identification in anti-cancer research. Novel SL screening analysis and the use of highly curated databases would contribute to improve the results of this methodology

Exploring the randomness of Directed Acyclic Networks

The feed-forward relationship naturally observed in time-dependent processes and in a diverse number of real systems -such as some food-webs and electronic and neural wiring- can be described in terms of so-called directed acyclic graphs (DAGs). An important ingredient of the analysis of such networks is a proper comparison of their observed architecture against an ensemble of randomized graphs, thereby quantifying the {\em randomness} of the real systems with respect to suitable null models. This approximation is particularly relevant when the finite size and/or large connectivity of real systems make inadequate a comparison with the predictions obtained from the so-called {\em configuration model}. In this paper we analyze four methods of DAG randomization as defined by the desired combination of topological invariants (directed and undirected degree sequence and component distributions) aimed to be preserved. A highly ordered DAG, called \textit{snake}-graph and a Erd\:os-R\'enyi DAG were used to validate the performance of the algorithms. Finally, three real case studies, namely, the \textit{C. elegans} cell lineage network, a PhD student-advisor network and the Milgram's citation network were analyzed using each randomization method. Results show how the interpretation of degree-degree relations in DAGs respect to their randomized ensembles depend on the topological invariants imposed. In general, real DAGs provide disordered values, lower than the expected by chance when the directedness of the links is not preserved in the randomization process. Conversely, if the direction of the links is conserved throughout the randomization process, disorder indicators are close to the obtained from the null-model ensemble, although some deviations are observed.Comment: 13 pages, 5 figures and 5 table

Barley-ß-glucans reduce systemic inflammation, renal injury and aortic calcification through ADAM17 and neutral-sphingomyelinase2 inhibition

In chronic kidney disease (CKD), hyperphosphatemia-induced inflammation aggravates vascular calcification (VC) by increasing vascular smooth muscle cell (VSMC) osteogenic differentiation, ADAM17-induced renal and vascular injury, and TNFα-induction of neutral-sphingomyelinase2 (nSMase2) to release pro-calcifying exosomes. This study examined anti-inflammatory β-glucans efficacy at attenuating systemic inflammation in health, and renal and vascular injury favoring VC in hyperphosphatemic CKD. In healthy adults, dietary barley β-glucans (Bβglucans) reduced leukocyte superoxide production, inflammatory ADAM17, TNFα, nSMase2, and pro-aging/pro-inflammatory STING (Stimulator of interferon genes) gene expression without decreasing circulating inflammatory cytokines, except for γ-interferon. In hyperphosphatemic rat CKD, dietary Bβglucans reduced renal and aortic ADAM17-driven inflammation attenuating CKD-progression (higher GFR and lower serum creatinine, proteinuria, kidney inflammatory infiltration and nSMase2), and TNFα-driven increases in aortic nSMase2 and calcium deposition without improving mineral homeostasis. In VSMC, Bβglucans prevented LPS- or uremic serum-induced rapid increases in ADAM17, TNFα and nSMase2, and reduced the 13-fold higher calcium deposition induced by prolonged calcifying conditions by inhibiting osteogenic differentiation and increases in nSMase2 through Dectin1-independent actions involving Bβglucans internalization. Thus, dietary Bβglucans inhibit leukocyte superoxide production and leukocyte, renal and aortic ADAM17- and nSMase2 gene expression attenuating systemic inflammation in health, and renal injury and aortic calcification despite hyperphosphatemia in CKD.A grant to A.S.D. and M.J.M. from IRBLleida and Agrotecnio Research collaborative projects from the Consell Social at Lleida University supported initial work, Instituto de Salud Carlos III and co-funded by European Union (ERDF/FEDER) (FIS PI11/00259, PI14/01452, PI17/02181), Plan de Ciencia, Tecnología e Innovación 2013–2017 y 2018–2022 del Principado de Asturias (GRUPIN14-028, IDI-2018-000152), RedInRen from ISCIII (ISCIII-RETIC REDINREN RD16/0009). Investigator support included: NC-L by GRUPIN14-028 and IDI-2018-000152, LM-A by GRUPIN14-028, SP by FICYT; MVA and PV by Educational Grant 2 A/2015 from ERA-EDTA CKD-MBD Working Group; PV and AC by ERA-EDTA fellowships 2011 and 2012; JR-C by MINECO (“Juan de la Cierva” program, FJCI-2015-23849); A.S.D. by Asociación Investigación de Fisiología Aplicada. A.S.D. and M.J.M. are members of the Campus Iberus (Ebro Valley Campus of International Excellence)