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XII Congreso Anual de Biotecnología 2018
Libro de Resúmenes. XII Congreso de la Federación Española de Biotecnólogos - Congreso Anual de Biotecnología.Girona, 11-14 de julio de 2018
EditaFederación Española de BiotecnólogosCampus de Vegazana s/n24071 – León
AutoresAitor BalmasedaJuan CalvetÓscar Moreno
EditorAitor Balmaseda
Diseño y MaquetaciónAitor BalmasedaÓscar Moreno
ISBN 978-84-606-9600-1
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Índice de contenidos
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Índice de contenidosÍndice de Contenidos............................................................................... 7Bienvenida ................................................................................................. 11Prólogo ....................................................................................................... 15Comités ...................................................................................................... 19
Comité Científico ........................................................................... 21Comité Organizador ...................................................................... 23
Programa ................................................................................................... 25bioBAC: ....................................................................................................... 29businessBAC: ............................................................................................. 43
Mesas redondas ............................................................................. 54Transferencia de tecnología ............................................. 54Sesión Startups ................................................................... 56
expoBAC ..................................................................................................... 59MALOLACTIC FERMENTATION PERFORMANCE OF OENOCOCCUS OENI STRAINS IS DIFFERENTLY AFFECTED BY NON-SACCHAROMYCES YEAST LEES ............................................................................................................62A MICROTITER PLATE METHOD TO CONFIRM THE CLASSIFICATION OF SHERRY WINE YEASTS .............................................................................64VIRTUAL BIOPSY: DEVELOPMENT OF NON-INVASIVE IMMUNOTARGETED IMAGING AGENTS FOR THE DIAGNOSIS OF GLIOBLASTOMA ..........66THE EFFECT OF COLLAGEN-BASED EXTRACELLULAR MATRIX CONCEN-TRATION AND TGF-B IN 3D CANCER DISSEMINATION: A MICROFLUIDIC APPROACH ................................................................................................68DEVELOPMENT OF PROGRAMMABLE PLANT TRANSCRIPTIONAL ACTIVA-TORS BASED ON CRISPR /CAS9 ............................................................70PREDICTION OF STABILIZING POINT MUTATIONS IN PROTEIN STRUCTU-RES USING RATIONAL FEATURES IN A MACHINE LEARNING WORKFLOW 72CHARACTERIZATION OF PHOTOSWITCHABLE HYDROPHOBIC AND AM-PHIPHILIC PEPTIDES FOR FOLDING AND MEMBRANE INSERTION STU-DIES ............................................................................................................74BIOSYNTHESIS OF BETAXANTHINS BY ELICITATION WITH MEJA AND SA IN CELL CULTURES OF AMARANTHUS HYPOCHONDRIACUS VAR. NUTRI-
Índice de contenidos
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SOL .............................................................................................................76PRODUCTION OF PTEROSTILBENE IN METABOLICALLY ENGINEERED GRAPEVINE CELL CULTURES WITH ROSA HYBRIDA ORCINOL O-METHYL TRANSFERASE ..........................................................................................78IN SILICO BINDING SITE DETECTION IN ABCC3 FOR PHARMACOPHO-RE-BASED DRUG DESIGN .......................................................................80MYCO-MIGE: OPTIMIZATION OF A NEW POWERFUL TOOL FOR MYCOBAC-TERIAL GENOME ENGINEERING ...........................................................82INHIBITION OF HIF-1a/BNIP3 AXIS AND HYPOXIA-MEDIATED MITOPHAGY BY MELATONIN ADDITION ENHANCES HUMAN HEPATOCELLULAR CAR-CINOMA CELLS SENSITIVITY TO SORAFENIB TREATMENT ..............84BIBLIOGRAPHIC REVIEW OF CELLULAR DIFFERENTIATION OF OMMATI-DIUM IN DROSOPHILA MELANOGASTER.............................................86THE ROLE OF FURC IN THE RESPONSE OF ANABAENA PCC7120 TO OXI-DATIVE STRESS .........................................................................................88UNC0642 EPIGENETICALLY ACTIVATES AUTOPHAGY AND MODULATES THE CELLULAR CHARACTERISTICS AND SURVIVAL OF U2OS CELLS 90CHARACTERIZATION OF KLEBSIELLA PNEUMONIAE BACTERIOPHAGES WITH BIOTECHNOLOGICAL POTENTIAL .............................................92MULTI-STABILITY OF BLOOD CIRCULATION IN LADDER-SHAPED NE-TWORKS ....................................................................................................94SYNTHESIS AND EVALUATION OF THE BIOLOGICAL ACTIVITY OF LIPO-PEPTIDES DERIVED FROM BP100 CONTAINING A D-AMINO ACID ..96SEMINAL PLASMA FROM BOARS WITH HIGH RESISTANCE TO COLD SHOCK COULD IMPROVE POST-THAWING SPERM QUALITY ...........98IDENTIFICATION OF NOVEL TARGETS FOR ANTI-PSEUDOMONAS AEUR-GINOSA THERAPIES ................................................................................100
viveBAC ....................................................................................................... 103Cursos de formación ..................................................................... 104
En las diferentes ediciones del congreso se han realizado Design Thinking .................................................................. 105Bioinformática ..................................................................... 105Taller de desarrollo personal y profesional ................... 106Seminario Gestión de proyectos ..................................... 106
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Programa Social ............................................................................ 107Visitas ............................................................................................... 110
Sincrotrón Alba ................................................................... 111Asambleas Generales de FEBiotec ....................................................... 113Índice de Autores ...................................................................................... 118
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Bienvenida
Gracias a todos.
Como ya sabréis, en FEBiotec celebramos, con el BAC 2018, nuestro décimo ani-versario. Y si hemos llegado hasta aquí ha sido gracias a la contribución de cada uno de nosotros. La contribución de los que hemos estado a primera línea de la Federación, de los que ayudábamos a las comisiones y de aquellos que, colabo-rando o no, han confiado siempre en FEBiotec como entidad que representa a los biotecnólogos y defiende la biotecnología.
Ha costado mucho llegar hasta aquí. Muchas han sido las horas de trabajo volunta-rio, durante mucho tiempo, siempre con la incertidumbre de si merecería la pena. Este dossier demuestra que así ha sido. Hemos llevado la biotecnología y sus apli-caciones a prácticamente cualquier rincón de España, hemos defendido nuestra valía ante cada convocatoria de la que hemos sido excluidos, hemos abierto un debate social responsable sobre como la biotecnología ayuda a mejorar la vida de las personas y el medio ambiente.
Y seguiremos trabajando en esta dirección. Nuestro décimo congreso, BAC 2018, será la celebración de estos 10 años en los que hemos trabajado juntos para llegar más lejos.
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Bienvenida
En el momento de escribir estas líneas, la biotecnología representa el mismo por-centaje de PIB que el sector del turismo. Quizás ha llegado el momento de que de-jemos de decir que España es un país de turismo y empecemos a decir que es un país de Biotecnología. Está en nuestras manos conseguirlo, tenemos la capacidad y la motivación.
Como sabéis, es habitual que en los congresos de FEBiotec (que evolucionaron de los iniciales congresos interuniversitarios a BAC) asistan entre trescientos y cuatro-cientos asistentes, además de ser más de mil socios. Os hemos convocado a asistir a los congresos de León, Gijón, Salamanca, Sevilla, Barcelona, Madrid, Tarragona, Valencia… Ahora os pedimos que nos acompañéis a Girona, junto con asistentes de toda España y Latinoamérica, y ponentes galar-donados con premios Nobel y referentes internacionales en el campo de la biotec-nología.
Nos vemos en Girona para celebrar nuestro décimo aniversario. Y como siempre, orgullosos de ser Biotecnólogos
Imma Prats MorillaPresidenta de FEBiotec
Codirectora de BAC 2018
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Prólogo
11 EDICIONES… Después de once ediciones del Congreso Anual de Biotecnología de la Federación Española de Biotecnólogos (BAC), nos sentimos con capacidad de afirmar que he-mos establecido una referencia en España.Por el congreso han pasado premios Nobel como Ada Yonath, Robert Huber, Wer-ner Arber o Jack Szotack. También hemos tenido el placer de tener ponentes con una larga carrera en el sector como Tom Dodd (pionero en la obtención de plantas transgénicas), Marc Van Montagu (expresidente de la European Federation of Bio-technology y la Public Research and Regulation Initiative).
BAC 2018 se sustenta en 4 ejes temáticos, de manera que cada persona que asista puede diseñar su propio itinerario, bien sea apostando por hacer todas las activi-dades de un único eje o por la combinación de los cuatro.
Estos ejes se llaman bioBAC, businessBAC, expoBAC y viveBAC. Mientras que los tres primeros son el cuerpo de BAC y constituyen todos los bloques de ponencias, que discurren a la vez paralelamente (salvo unas pocas conferencias plenarias, como las mesas de debate o la ponencia del galardonado con un Nobel); viveBAC es todo el conjunto de actividades que hay alrededor: cursos de formación, visitas científicas, actividades de networking y, incluso, programa social. viveBAC discurri-rá las tardes de los dos primeros días que se hagan ponencias (11 y 12 de julio) y los días previos.
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Este congreso se enmarcará dentro de la celebración del 10º aniversario de la Fe-deración y es por esto que esta celebración se acompañará durante todos los días del congreso. Con una celebración pensada para elúltimo día del evento, se harán diversas actividades para dar a conocer la trayecto-ria de FEBiotec así como invitar a los impulsores de la federación y a las diferentes juntas directivas que han hecho posible que FEBiotec se convierta en uno de los referentes de la biotecnología en España.
Imma Prats MorillaPresidenta de FEBiotec
Codirectora de BAC 2018
Prólogo
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del congreso anual de biotecnología 2018
COMITÉS
Comité Científico
Microbiología clínicaMargarita [email protected]
Ingeniería de proteínasMark Ribó[email protected]
ImmunologíaAnna Masaller [email protected]
Biologia sintética y OncologíaAntoni [email protected]
Mejora genética asistida con biomarcadores Oriol [email protected] Luis Garcí[email protected]
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Comité Científico
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Biotecnología vegetalMercè [email protected]
Biotecnología de la reproducciónM. Dolores [email protected]
Biotecnología vegetalOlga [email protected]
Comité Organizador
DIRECCIÓNPablo OrtizImma Prats
RESPONSABLES DE COMISIONES DE TRABAJO
Dirección RegionalJudit Rovira
expoBACAitor Balmaseda
Juan Calvet
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businessBACArturo BlázquezYago Juste
bioBACLuís Getino
Raquel LedoEduardo Moreno
Diseño y webAitor BalmasedaÓscar MorenoPablo Ortiz
Programa
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bioBAC:Ponentes
bioBAC hereda todas las ponencias científicas que se han vi-vido a lo largo de las diversas ediciones de BAC y de la marca precedente, el Congreso Interuniversitario de Biotecnología. Si bien, la nueva marca BAC permitió llegar a nuevo público interesado en la investigación más senior, ahora propone-mos llegar también a públicos más enfocados a la industria biotecnológica. Es por esto que nace la necesidad de crear una marca única y diferenciada para aquellas ponencias que son de carácter exclusivamente científico: bioBAC.
Respecto a ediciones anteriores también se ha decidido acor-tar la duración total de las exposiciones a 45 minutos. De esta manera, se puede dar cabida a más ponencias en el mismo tiempo (sin que esto implique una disminución de la calidad), es mejorar la atención del público y da al congreso un mayor dinamismo. Este tiempo se distribuirá en 30 minutos de expo-sición de la persona encargada de la ponencia y 10 pregun-tas. Los 5 restantes se aprovecharán para facilitar el cambio entre ejes a todas aquellas personas que estén interesadas.
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Ada YonathLa Dra. Ada Yonath es licenciada en Química por la Universidad Hebrea de Jerusalén (1965) con un M.Sc en Biofísica. Doctorada en Cristalogra-fía de Rayos X en el Instituto Weiz-man de Ciencias de Israel, realizó estudios postdoctorales en la Uni-versidad de Carnegie-Mellon (Pitts-burg) y en el Instituto Tecnológico de Massachusetts (MIT) donde tra-bajó en la estructura de nucleasas.
A finales de 1970 regresó al Instituto Weizmann y constituyó el primer la-boratorio de cristalografía biológica del país. Fue pionera en el desarrollo de la cristalografía del ribosoma que le permitió desentrañar la estructu-ra tridimensional del ribosoma y su función vital en la biosíntesis protei-ca. Esta investigación básica ha teni-do una gran repercusión terapéuti-ca, pues ha revelado el mecanismo de acción de varios antibióticos que
atacan los ribosomas de las bacterias para inhibirlas.
La investigación de la Dra. Yonath ha sido reconocida con diferentes galardones:: en 2007 recibió el Premio Wolf en Química, en 2008 fue doblemente galardonada con el Premio L’Oréal-UNESCO a Mujeres en Ciencia y el Premio Mundial de Ciencias Albert Einstein. Y, en 2009, recibió el Premio Nobel de Química junto al indio Venkatraman Ra-makrishnan y el estadounidense Thomas Steitz por su trabajo donde descifró, mediante cristalografía de rayos X, la base estructural de la se-lección de los antibióticos y mostró el papel clave en la utilidad clínica y la eficacia terapéutica, preparando así el camino para la estructura de base del diseño de fármacos.
Ada Yonath
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Pedro GuerreroRedactor y divulgador de nuevas tecnologías y crítico de videojuegos. También da talleres de hablar en público y es cofundador de Ludolo-gía BCN, microempresa de gamifi-cación pedagógica…
“Mujeres, ciencia y rock&roll” es una breve y concisa charla donde analizaremos los aspectos más re-levantes del papel de la mujer ac-tual dentro de la industria científica y tecnológica en contraste con la imagen mostrada en la ficción den-tro del marco de la cultura del privi-legio.
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Anna Laromaine SagueTítulo: “Controlling the nanostruc-turation and composition to crea-te functional composites of bacte-rial cellulose”
Doctora en Química por el Instituto de Ciencia de Materiales de Barcelo-na (ICMAB, CSIC), en el cual trabaja actualmente en el grupo de Na-noparticles and Nanocomposites. Con varios periodos en el extranjero –Imperial College de Londres, Insti-tuto Tecnológico de Massachusetts (MIT), Universidad de Harvard – es experta en bionanotecnología.Actualmente su investigación se centra en el estudio de la interacción entre nanomateriales y estructuras biológicas in vitro (como células o tejidos) y in vivo en el nematodo Caenorhabditis elegans. Su trayec-toria profesional se combina con aventuras empresariales y activida-des en docencia y en divulgación.
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José Pío BeltránTítulo: “La producción de ali-mentos y la ingeniería genéti-ca”
Doctor en Ciencias Químicas por la Universidad de Valencia, es actualmente profesor de Investi-gación en el Instituto de Biología Molecular y Celular de Plantas (IBMCP, CSIC). Especializado en interacciones planta-patógeno y en genética del desarrollo en plantas, dirige el Laboratorio de Biología Reproductiva y Biotec-nología de Plantas del IBMCP. A lo largo de su carrera ha ostentado distintos cargos, entre ellos el de vicepresidente del CSIC.
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Penélope GarcíaPenélope García-Angulo attained the degree in Biological Sciences from the University of León (ULE) in 2001. One year later, she obtai-ned a predoctoral grant from the Ministry of Education and Science of Spain inside the University Teacher Training program (FPU). From April 2006 to date, she has been carr-ying out her work as a lecturer and researcher in the Plant Physiology Area of the ULE, first as an Assistant Professor (from 2006 to 2009); later, as an Associate Professor (from 2009 to 2014) and currently, as a Senior Lecturer.For years, Penélope García-Angulo research interest has been focused on plant cell wall polymers such as cellulose, hemicelluloses, pectins and lignin and their plasticity under stress situations as some of the cell wall mo-difications that take place during stress situa-tions could have important biotechnological applications. As part of this research, she has worked with in vitro cultures of different spe-cies (bean, maize, poplar, grape, hops…) and over the last 3 years, Penélope is the scienti-fic advisor-in-chief of Agrovet-Healthy Plants Biotechnological Institute which is a priva-te enterprise focused on the production of free-pathogen certified plants.
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Fátima BoschFátima Bosch i Tubert es doctora en Farmacia y catedrática de Bioquímica y Biología Molecular en la Universidad Autónoma de Barcelona, donde es responsable del Centro de Biotecnolo-gía Animal y Terapia Génica (CBATEG). Cuenta con más de un centenar de publicaciones y diversos premios a la investigación. Fue vicepresidente de la European Association for the Study of Diabetes (EASD), y es miembro de distintas sociedades y asociaciones li-gadas a la enfermedad.
Su grupo de investigación se centra en la diabetes mellitus y la obesidad, contando con líneas centradas tanto en el estudio de las causas y la fisio-patología de estos trastornos, como en el desarrollo de nuevas estrategias terapéuticas a los mismos basadas en la terapia génica. Asimismo, utilizan su experiencia en la terapia génica para desarrollar el tratamiento de enferme-dades raras, como las mucopolisacari-dosis tipo II y III.
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David CaparrósDavid Caparrós es un investigador del Centro de Investigación en Genó-mica Agrícola (CRAG, por sus siglas en inglés). Trabaja en el programa de metabolismo e ingeniería metabóli-ca, dentro del grupo de “Bioingenie-ría de biomasa lignocelulósica en el maíz”. Tras su período de Investigador Ramón y Cajal y profesor asociado, es actualmente investigador titular de su mencionado grupo.
Su trabajo se centra en el estudio de la lignina de la pared celular del maíz y los genes que la afectan. Esto per-mitirá el desarrollo de nuevas líneas de maíz con mejoras nutricionales, y una mejor calidad lignocelulósica, lo que puede utilizarse para la produc-ción de nuevos combustibles no fósi-les como el bioetanol.
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María Vallet RegíMaría Vallet Regí es catedrática de Quí-mica Inorgánica de la Facultad de Far-macia de la Universidad Complutense de Madrid. Tiene una amplia carrera in-vestigadora, con distintos premios acre-ditándola, como la medalla de oro de la Real Sociedad Española de Química (2011), de la cual fue Vicepresidenta en el período 1999-2007. También cuenta con el premio de investigación “Miguel Cata-lán” (2013) y es Doctora Honoris Causa por la Universidad Jaume I.
Cuenta con más de medio millar de pu-blicaciones y ha liderado numerosos proyectos tanto nacionales como inter-nacionales. Su trabajo abarca distintas líneas de investigación, centrados en la aplicación biológica y biotecnológica de los materiales nanoestructurados. De en-tre sus proyectos más recientes, destaca una “Advanced Grant” concedida por el Consejo Europeo de Investigación (ERC, por sus siglas en inglés), dedicada a desa-rrollar un “nanosistema mesoporoso po-livalente para enfermedades del hueso”.
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María del Carmen Marín Título: “Nueva función del gen Trp73 como arquitecto tisular”
Profesora titular de la Universidad de León en Departamento de Biología Molecular, Área de Biología Celular, dirige el grupo de investigación consolidado de la Junta de CyL (UIC157) y fue subdirectora del IBIO-MED del 2007-2018. Licenciada en Ciencias Biológicas en la Universidad de Salaman-ca, realizó su tesis doctoral en el MD Ander-son Cancer Center. Su trabajo se centró el estudio de las interacciones funcionales de los genes p53 y bcl-2 y fue subvencionada por una beca del Instituto Nacional de Sa-lud (NIH) de EEUU.Realizando su trabajo post-doctoral en el Dana Farber Cancer Institute (Harvard University), demostró por primera vez, la función pro-apoptótica de p73, el primer homólogo identificado del gen supresor tumoral p53, su función en la regulación de E2F y en la respuesta a quimioterapia y su interacción con mutantes de p53. Des-de su incorporación a la ULE ha diseñado y dirigido 19 proyectos de investigación.
businessBAC:Ponentes
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businessBAC nace de la creciente necesidad de la inte-gración de la ciencia con el mundo empresarial. Con el mismo esquema que bioBAC, businessBAC se centrará en la exposición de las últimas tendencias del sector bio-tecnológico orientadas al negocio.
Así, podemos encontrar las últimas tendencias en lide-razgo o business development, cuál es la situación de las nuevas empresas que quieren salir al mercado o cuáles son las mayores dificultades actuales a la hora de paten-tar, hacer marketing o market access.
El valor añadido de este eje, que recoge una temática que ya había ido apareciendo de una u otra manera en anteriores ediciones de BAC, es la formalización como a eje propio, de manera que se dota de mayores recursos y un enfoque especializado además de permitir desarrollar actividades más centradas en el área de business en el eje viveBAC.
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José Antonio MesaTítulo: “Financiación privada para empresas del sector biosanitario”
Jose Antonio es el Director de Inversiones en Caixa Capital Risc. Se especializa en inversiones en biotecnología y dispositivos médicos. Actual-mente es miembro del Consejo de Administra-ción de Laboratoris Sanfit, Aelix Therapeutics, STAT Dx, mTrap y Genmedica Therapeutics. Es responsable del análisis, negociación y estruc-turación de procesos en empresas de ciencias de la vida. José A. tiene más de 10 años de expe-riencia en el análisis de oportunidades de inver-sión y se especializa en la creación de empresas en el sector de la salud.Su experiencia comenzó en el Departamento de Desarrollo de Negocios en Genzyme Corpo-ration, una compañía especializada en el desa-rrollo y comercialización de medicamentos para enfermedades huérfanas. Más tarde se unió al equipo de Technology Portfolio de Genoma España, una fundación del sector público que promueve el desarrollo tecnológico, la transfe-rencia de conocimiento y la innovación, particu-larmente en el sector biotecnológico, donde se especializó en el análisis de oportunidades de inversión en empresas de nueva creación. José Antonio es licenciado en Biología y tiene un Más-ter en Finanzas Corporativas por la Universidad Complutense de Madrid (UCM), un MBA y PDD IESE de la Universidad de Navarra.
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María José Borreguero Figols
María José Borreguero es doctora en Economía y Empresa por la Universi-dad de Barcelona y Máster en Comer-cio y Finanzas internacionales (UB). En sus más de diez años de experiencia como consultora, ha asesorado a más de 150 empresas en sus procesos de internacionalización dentro de los programas subvencionados por ICEX, ACC10, IDE y Cámaras de Comercio.Uno de sus campos de especialización son los procesos de internacionaliza-ción de empresas tecnológicas, tra-bajando como experta evaluadora en el programa europeo HORIZON 2020 SME Instrument, FTI y Eurostars-Eure-ka.Es conferenciante en las principales universidades y escuelas de negocio de España y profesora asociada de la Universidad Politécnica de Cataluña y la Universidad de Barcelona, en el de-partamento de Economía y Organiza-ción de empresas.
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Jorge BarreroTítulo: “Innovación para un futuro más hu-mano“
Director General de la Fundación Cotec. Li-cenciado en Bioquímica por la Universidad de Salamanca, Máster en Estudios de Cien-cia, Tecnología y Sociedad por esa misma Universidad, ha cursado estudios de postgra-do en Dirección de Industria Farmacéutica y Liderazgo en la Gestión Pública en las Escue-las de Negocio IE e IESE.Desde 2008 a 2012 desempeñó el cargo de Director General del Gabinete de la Ministra de Ciencia e Innovación, Cristina Garmendia, ejerciendo funciones en la coordinación ge-neral de la actuación política del Ministerio, y supervisando la agenda pública, la actividad parlamentaria y las relaciones con los medios de comunicación, y una vez finalizada esta etapa regresó como adjunto a la presidencia de ASEBIO, donde fue secretario general du-rante los años 2006 al 2008. Con anterioridad, había desarrollado su carrera en el ámbito de la consultoría estratégica en el sector biotec-nológico y en el sistema público de I+D. Ba-rrero colabora habitualmente con numero-sos medios de comunicación y ha impartido docencia en varias universidades y escuelas de negocios.
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Alice NewtonTítulo: “Why Europe needs a strate-gy for Bioeconomy“
Alice Newton is a tenured Professor at the Department of Earth, Envi-ronmental and Marine Sciences of the University of Algarve, Portugal and a researcher at the NILU-De-partment of Environmental Impacts and Sustainability. Her work bridges Science-Policy and she has been a consultant to national governments (Portugal, Norway, Denmark, USA) as well as the EC, (Joint Research Centre, DG Environment and DG Re-search and Development). In 2016 and 2017, Alice was Chairperson of the expert group reviewing the Bioe-conomy Strategy for the European Commission.
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Paola SalanuevaTítulo: Oportunidades Profesiona-les en el sector de la Biotecnología: El caso de HISTOCELL, Medicina Re-generativa
Paola Salanueva es Directora de Re-cursos Humanos del holding biotec-nológico vasco “Noray Biosciences Group”. Desde hace diez años, se res-ponsabiliza del área de desarrollo de personas en “Histocell S.L.” empresa biofarmacéutica vizcaína dedicada a la medicina regenerativa que emplea a personas de alta cualificación en el ámbito de la ciencia y la tecnología.
Además, es graduada en Derecho por la Universidad de Deusto y postgra-duada en gestión del talento en redes sociales por la Innovation & Entrepre-neurship Business School.
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Ion ArocenaTítulo: “Situación y tendencias del sec-tor de la biotecnología en España”
Ion Arocena es Licenciado en Biología por la Universidad Complutense de Ma-drid con Premio Extraordinario (2003) y Master MBA por la EOI (2010). Cuenta con años de experiencia en evaluaciones científico-técnicas y de viabilidad comer-cial de tecnologías, proyectos y empre-sas en el ámbito de la biotecnología.
Trabajó como Técnico de Vigilancia Tec-nológica en el Círculo de Innovación en Biotecnología/OTRI UAM (2004- 2005) y Técnico de Evaluación y Comercializa-ción en Genoma España (2005-2006). Posteriormente, fue socio y Director de Inversiones de la firma de capital riesgo especializada en biotecnología, SUAN-FARMA Biotech SGECR y consejero-re-presentante en Agrenvec, Vivia Biotech y Clavesuan. Desde 2016 es Director Gene-ral de ASEBIO, la Asociación Española de Bioempresas.
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Pablo is the Head the Technology and Business Development Office activities where he channels CRG´s discoveries to market. He has over 14 years of research and development experience in Drug Discovery, Synthetic Biology and Protein Therapeutics, and 10 years managing technology transfer and commercialization processes in areas such as geno-mics, protein therapeutics, gene therapy, cell therapy, live bio therapeutics, etc. Dr. Cironi has acquired a unique and strong acumen in strategy and innovation, and serves on seve-ral boards of renowned health research institutions.Prior to his appointment at Center for Genomic Regulation, Pablo was Senior Innovation & Technology Transfer Manager at the Botín Foundation, one of the nation’s largest philan-thropy where he was responsible for identifying new business opportunities, managing the IP portfolio and defining business strategies to accelerating developments of scientific discoveries into viable innovations to improve health, wellbeing, and geared towards so-cioeconomic impact.Pablo holds a B.Sc. in Chemistry from the University of Buenos Aires and a Ph.D. in Orga-nic Chemistry from the University of Barcelona. He was a postdoctoral Fulbright Fellow at the Department of Systems Biology at Harvard University from 2005 to 2009, during which he worked on different aspects of Synthetic Biology, Protein Design and Engineering, in addition to successfully developing a novel technology for designing novel protein thera-peutics.
Pablo Cironi
Jorge Barrero
Mesas redondas
Director General de la Fundación Cotec. Licenciado en Bioquímica por la Universidad de Salaman-ca, Máster en Estudios de Ciencia, Tecnología y Sociedad por esa misma Universidad, ha cursado
Transferencia de tecnologías Maximizando el retorno de la ciencia, ¿hablamos de transferencia?
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Mesas redondas
Doctor (Farmacología) y Licenciado con Grado (Farmacia, Espec. Bioquímica) por la Univ. de Bar-celona. Posición actual: Director de Ferrer Advanced Biotherapeutics (Ferrer). Posiciones previas: Biotechnology and Biological Sciences, Director (Ferrer); R&D Director & Member of the Board (Sal-vat); Associate Director of Discovery (Almirall); Profesor Asociado de Biología Celular (UAB); Head of Pharmacology (Almirall). Ha ejercido responsabilidades ejecutivas y/o científicas en equipos que han desarrollado y lanzado al mercado: 5 nuevas entidades moleculares (UE/EEUU/ASIA); 1 nue-va entidad terapéutica (UE/EEUU) y 1 nuevo producto de diagnóstico molecular en oncología en Europa. Es co-autor de más de 40 publicaciones en revistas con revisión por pares, 110 comunica-ciones y conferencias y es co-inventor de 18 solicitudes de patentes. Ha dirigido dos tesis doctora-les. Ex-Presidente del Comité de Programas de la Unión Internacional de Farmacología (IUPHAR). Ex-Miembro de la Junta Directiva de ASEBIO. Presidente de la Sociedad Catalana de Biotecnología Médica. Miembro del Expert Panel y Mentor en el Programa CaixaImpulse. Miembro del Comi-té Científico Asesor de BIONAND. Ha actuado como miembro del Comité Científico de múltiples congresos y reuniones. Miembro del Jurado de varios Premios Científicos. Conferenciante invitado en numerosos eventos científicos y académicos. Intereses actuales: Innovación abierta & Investiga-ción en colaboración. Terapias avanzadas. Neurofarmacología. Oftalmología. Diagnóstico molecu-lar. Políticas de investigación y sostenibilidad.
Andrés Fernández
estudios de postgrado en Dirección de Industria Farmacéutica y Liderazgo en la Gestión Pública en las Escuelas de Negocio IE e IESE.Desde 2008 a 2012 desempeñó el cargo de Director General del Gabinete de la Ministra de Ciencia e Innovación, Cristina Garmendia, ejerciendo funciones en la coordinación general de la actuación política del Ministerio, y supervisando la agenda pública, la actividad parlamentaria y las relaciones con los medios de comunicación, y una vez finalizada esta etapa regresó como adjunto a la presi-dencia de ASEBIO, donde fue secretario general durante los años 2006 al 2008. Con anterioridad, había desarrollado su carrera en el ámbito de la consultoría estratégica en el sector biotecnológico y en el sistema público de I+D. Barrero colabora habitualmente con numerosos medios de comu-nicación y ha impartido docencia en varias universidades y escuelas de negocios.
Transferencia de tecnologías Maximizando el retorno de la ciencia, ¿hablamos de transferencia?
Veterinaria, máster en inmunolgía y doctorado en farmacologia (estancia de 1 año en el National Institute of Health de Bethesda). Inicié mi etapa emprenedora a raíz de mi pos-doctorado en el Instituto de Investigación Biomédica de Girona (IDIBGi) i complementé mi formación con un Programa de Desarrollo Directivo en IESE (PDD).
Actualmente, soy cofundadora y CEO de GOODGUT, miembro de Consejo Social de la Universitat Autònoma de Barcelona, donde presido la comisión Universidad- Empresa, y miembro de la junta directa de l’AENTEG.
Mariona Serra
Es Ingeniero Industrial Mecánico por la UPC y ha cursado un PDD por ESADE. Posee más de 25 años de experiencia en la gestión de varias áreas empresariales: desarrollo de pro-ducto, desarrollo de negocio, análisis y estrategia, product management, marketing y ventas.
Ha trabajado más de 8 años en el campo de dispositivos médicos y equipos de laborato-rio desarrollando una nueva línea de negocio dentro de una multinacional. Dispone de un excelente conocimiento de la cadena de valor global del sector desde la detección de la necesidad del mercado hasta la comercialización y servicio postventa, especialmente en equipos complejos de automatización del laboratorio de microbiología y dispositivos médicos para terápias de medicina regenerativa.
Josep M. Escuer
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Sesión Startups Biotech-up: Jóvenes empresas del sector biotecnológico
Joan es un emprendedor, co-fundador de la empresa Cebiotex (www.cebiotex.com). Durante más de 8 años ha estado trabajando en la I&D+i de un nuevo material textil (na-no-fibras), orientado al uso Biomédico. En Octubre de 2013 deja sus responsabilidades como Director de Operaciones en la empresa Indesmalla (www.indesmalla.com) para incorporarse a Cebiotex como CEO. Actualmente, junto con el equipo, que ha logrado for-mar alrededor del proyecto Cebiotex (Médicos Oncológicos, Cirujanos, Farmacéuticos, In-genieros, Biotecnologías, Financieros, UPC, HSJD) está desarrollando el primer producto, CEB-01, como “local drug delivery system” para uso oncológico. Cebiotex fue el 2º finalista del BioEmprendedorXXI de 2013.
Joan tiene una sólida formación tecnológica, industrial y empresarial. Como Ingeniero Textil, trabajó durante 12 años en el Departamento de I&D+i de la empresa fabricante de maquinaria textil Jumberca. Así mismo, su formación en Masters de Dirección de Opera-ciones (EADA www.eada.edu) y MBA (ICT www.ict.edu), le han permitido liderar con éxito Proyectos Industriales de Re-estructuración, Organización y Dirección en empresas como Penn Elastic www.penelastic.com; Punto Blanco www.puntoblanco.com; Realts www.relats.com . Durante dichos proyectos ha formando y liderando equipos de mas de 180 colaboradores; instalaciones de más de 12.000 m2; +200 telares y equipos industriales; coordinado y diseñado +100 nuevos tejidos/año; producido +40.000 Kg semanales de tejidos técnicos; ….
Joan Bertran
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Sesión Startups Biotech-up: Jóvenes empresas del sector biotecnológico
expoBAC
Pósters y comunicacio-nes orales
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expoBAC se podría definir como el eje de BAC donde reunir a los jóvenes investigadores de los proyectos actuales.
Respecto a otras ediciones, se decide dar un espacio propio a este eje. Comunicaciones escritas y comunicaciones orales de los resúmenes seleccionados por el Comité Científico.
Las sesiones orales constarán de dos ponencias de 15 minutos y 5 minutos para preguntas después de cada una, de temáticas relacionadas. Como siempre, al final se contemplan 5 minutos de margen para facilitar el cambio de espacio. 14 ponentes serán los que darán voz a estas sesiones orales de expoBAC.
Para dar más valor añadido a este apartado del congreso, ade-más de dar la oportunidad de presentar la investigación de los ponentes mediante la sesión de posters y de interactuar con los asistentes, se organizará un concurso. Éste se basará en la buena capacidad comunicativa, más que en la calidad de la investiga-ción que ya ha sido garantizada previamente.
Los mejores abstracts se publicarán en un suplemento de la revis-ta BMC Biotechnology.
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MALOLACTIC FERMENTATION PERFORMANCE OF OENOCOCCUS OENI STRAINS IS DIFFERENTLY AFFEC-
TED BY NON-SACCHAROMYCES YEAST LEESBalmaseda, A., Bordons, A. and Reguant C.
Grup de recerca en Biotecnologia Enològica, Departament de Bioquímica i Biotecnologia, Facultat d’Enologia, Universitat Rovira i Virgili, Tarragona, Spain
Malolactic fermentation (MLF) of wine consists on the decarboxylation of L-ma-lic acid to L-lactic acid by lactic acid bacteria. Particularly, the main species of this process is Oenococcus oeni. Generally, MLF is positively affected when it is performed in presence of yeast lees, as result of an autolytic process of yeasts, which releases different compounds, such as nitrogenated compounds, glucans, mannoproteins or other yeast metabolites [1]. Nowadays, the use of non-Saccha-romyces yeasts in winemaking has increased because of their positive role in the organoleptic profile of wines, developing a new scenario where MLF has to take place [2].The aim of this work is to determine the fitness of different non-Saccharomyces yeast lees with the MLF performance by three O. oeni strains. For this purpose, a synthetic wine was supplemented with lees from different yeast strains (S. cerevi-siae, Torulaspora delbrueckii and Metschnikowia pulcherrima) and inoculated with O. oeni. Every 24h, L-malic acid consumption and bacterial viability was measured. O. oeni Viniflora CH11 was the fastest strain finishing the MLF, respect to the con-trol, when it was supplemented with all the 7 different yeast lees. Unexpectedly, PSU-1 and 13W1 O. oeni strains showed a slower MLF performance in presences of yeast lees suggesting a predilection for another energy substrate apart from L-malic acid. Furthermore, the consumption of citric acid was related with a bet-ter performance of the MLF, demonstrating its role in the adaptation of O. oeni to stress environment.
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These results will be complemented with the characterization of wines after su-pplementation in terms of protein (including mannoproteins) and polysaccharides concentration, amino acid profile, fatty acid and organic acid composition to better understand O. oeni’s behaviour.
References:[1] Guilloux-Benatier, M., Guerreau, J., and Feuillat, M. (1995). Influence of initial colloid content on yeast macromolecule production and on the metabolism of wine microorganisms. Am. J. Enol. Vitic. 46, 486–492.[2] Balmaseda, A., Bordons, A., Reguant, C. and Bautista-Gallego, J. (2018) Non-Saccharomyces in Wine: Effect Upon Oenococcus oeni and Malolactic Fer-mentation. Front. Microbiol. 9:534.
Funding:This work is supported by grant AGL2015-70378-R from Spanish Ministry of Eco-nomy and Competitiveness. AiB is grateful to the predoctoral fellowship 2018 FI_B 00501 from Generalitat de Catalunya.
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A MICROTITER PLATE METHOD TO CONFIRM THE CLASSIFICATION OF SHERRY WINE YEASTS
Hughes-Herrera, D., Cordero-Bueso, G., Ruíz-Muñoz, M., González, M., Bernal-Grande, M. and Cantoral J.M.
Department of Biomedicine, Biotechnology and Public Health, University of Cádiz, Cádiz 11510, Spain
Production of Sherry and Manzanilla wines follows two successive processes: firstly, an alcoholic fermentation of must by yeasts present on the surface of Vitis vinifera var. Palomino Fino in order to produce a “young” wine, and then, occurs a biological ageing of this wine by other veil-forming yeasts, also so-called yeasts of flor. Little is known about yeast diversity in the flor. Recent progress in molecular biology has led to the development of several techniques for yeast identification based on similarities or dissimilarities of DNA, RNA or proteins. However, these molecular techniques are insufficient in order to understand the real veil-forming yeast diversity within Sherry wines. The conditions present in biological ageing wine may influence the morphological and physiological characteristics of these yeast, causing ambiguous results in classical techniques that analysing the yeast gas production using Durham tubes.For this reason, we propose a rapid and reliable method, using a microtiter reader, to evaluate the fermentation and assimilation of carbon and nitrogen sources, the osmotolerance and the antibiotic resistance using 18 Saccharomyces cerevisiae and 5 non-Saccharomyces yeast strains for a correct identification and classifica-tion of the yeast present in the velum of flor complex. We used 96-well polysterene microplates and analysed the population growth in different mediums for 72 hours. With the compilation of data every hour, we observed its evolution, characterised and classified the different veil-forming yeast strains, according to the databases, in an economical and easily reproducible way. Yeasts were also analysed using
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the Microsatellite Multiplex PCR technique and the mitochondrial DNA restriction analysis, in order to confirm the correct yeast identification of our technique. Thus, the application of this simplified method using polysterene 96-well plates, is inex-pensive, low time consuming and efficient technique in combination with the mole-cular methods described above to ensure the veil-forming yeast diversity in Sherry wines.
References:[1] Ruíz-Muñoz, M.; Bernal-Grande, M.C.; Cordero-Bueso, G.; González, M.; Hu-ghes-Herrera, D.; Cantoral, J.M. A Microtiter Plate Assay as a Reliable Method to Assure the Identification and Classification of the Veil-Forming Yeasts during Sherry Wines Ageing. Fermentation 2017, 3, 58.[2] Kurtzman, C.; Fell, J.W.; Boekhout, T. The Yeasts: A Taxonomic Study; Elvesier: London, UK, 2011; p. 2363.[3] Barnett, J.A.; Payne, R.W.; Yarrow, D. Yeasts: Characterisation and Identifica-tion, 3rd ed.; Cambridge University Press: Cambridge, UK, 2000; p. 1139.
Funding:This work was financed by the project UCA18DGUEII02, and by the European Union’s Seventh Framework Programme via the Marie Curie Action, “Co-funding of Regional, National and International Programs” to stimulate research activities without mobility restrictions, co-financed by the ‘Junta de Andalucía’ and the Euro-pean Commission under grant agreement No. 291780
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VIRTUAL BIOPSY: DEVELOPMENT OF NON-INVASIVE IMMUNOTARGETED IMAGING AGENTS FOR THE
DIAGNOSIS OF GLIOBLASTOMARuiz-López, E.1, González-Gómez, R.1, Torres-Herrero, B.1, Naya-For-
cano, S.1, Magro, N.2, Romero, E.2, Tejero, H.3, Al-Shahrour, F.3, Morcillo, M.A.2, Schuhmacher A.J.1
1Aragon Health Research Institute (IIS ARAGON), Molecular Oncology Group, Zaragoza, Spain.2Research Centre for Energy, Environment and Technology (CIEMAT), Biomedical Applica-tions of Radioisotopes and Pharmacokinetics Unit, Madrid, Spain.3Spanish National Cancer Research Center (CNIO), Bioinformatics Unit, Madrid, Spain.
Glioblastoma (GBM) is the most common and aggressive brain tumor. Current diag-nosis of GBM by Magnetic Resonance Imaging (MRI) provides morphological, some-times inaccurate, information. A brain biopsy is finally often required [1]. One alterna-tive is Positron Emission Tomography (PET) but, unfortunately, the most widely used tracer, 18F-Fluorodeoxyglucose (18F-FDG), is ineffective due to the high consumption of glucose by the brain [2]. An innovative option is termed “immunotargeted imaging” [3]. By merging the high target selectivity and specificity of antibodies with the high spatial resolution, sensitivi-ty, and quantitative capabilities of PET, it is possible to conduct the non-invasive diag-nosis and monitoring of patients over time using in vivo, integrated, quantifiable, 3D, full body “immunohistochemistry”. ImmunoPET could be considered a virtual biopsy. Applying bioinformatics on patient datasets, we have identified molecular targets for the development of an immunoPET agent for GBM, due to the high levels of protein expression in GBM and negligible levels in normal brain. We are developing novel immunoPET agents against these candidates using murine monoclonal antibodies labeled with 89Zirconium in xenograft mice and “avatar” models. For clinical deve-lopment, we are reducing the radioactivity exposure and optimizing the blood brain barrier permeability of the tracers by generating different antibody fragments with faster clearance and pharmacokinetics [4]. As matching of the physical half-life of the
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positron-emitting radionuclide with the biological half-life of the antibody or fragment is crucial for immunoPET, these smaller derivatives will be labeled with PET isotopes of shorter half-lives, such as 68Galium, which advantageously can be produced in a generator rather than a cyclotron. Click chemistry by biorthogonal reactions in vivo allows the matching of other antibodies/fragments with tracers and thereby dimini-shes the exposure to radioactivity to ensure a better signal-to-noise ratio. We are ex-ploiting this approach to label multiple imaging tracers, including MRI-tracers, to the same pre-targeted molecule in vitro as well as multi-modal and multifunctional ima-ging and theragnostics. These imaging agents could be used for other tumor types and pathologies and may have a major impact on the diagnosis and monitoring of patients.
References:[1] Ahmed, R., et al., 2014. Malignant gliomas: current perspectives in diagnosis, treat-ment, and early response assessment using advanced quantitative imaging methods. Cancer management and research, 6:149-70.[2] La Fougère, C., et al., 2011. Molecular imaging of gliomas with PET: opportunities and limitations. Neuro Oncology, 13:806-19.[3] De Lucas, A. G., Schuhmacher, A. J., et al., 2016. Targeting MT1-MMP as an Im-munoPET-Based Strategy for Imaging Gliomas. PLoS One, 11(7):e0158634.[4] Freise, A. C., & Wu, A. M., 2015. In vivo imaging with antibodies and engineered fragments. Molecular Immunology, 67(2 Pt A):142-52.
Funding:Asociación Española Contra el Cáncer (AECC).Programa Ramón y Cajal (RYC).Fundación de Investigación Oncológica (FERO)
THE EFFECT OF COLLAGEN-BASED EXTRACELLULAR MATRIX CONCENTRATION AND TGF-B IN 3D CANCER
DISSEMINATION: A MICROFLUIDIC APPROACHJuste-Lanas, Y., Plou, J., Olivares, V., del Amo, C. , Borau, C., and Gar-
cía-Aznar J.M.
Multiscale in Mechanical and Biological Engineering, Aragon Institute of Engineering Re-search, Department of Mechanical Engineering, University of Zaragoza, 50018 Zaragoza, Spain..
Tumor cells are able to migrate from the original site to other places along the body, in a so-called metastatic process. The extracellular matrix is known to regulate their migration capability and it has been correlated with tissue-specific spreading pat-terns. Nevertheless, how the matrix affects these migration behaviors remains elu-sive [1, 2]. Here, through the use of microfluidic devices [3] and non-small cell lung cancer cells (H1299 cell line), we investigated how both 3D collagen-based matri-ces concentration and transforming growth factor-β (TGF-β) regulate the formation of cancer spheroids and promote tumor cell invasion capacity. Our results show that at low collagen concentrations, cancer cells migrate individually and have mo-derate invasion capacity, while on the contrary, when the collagen concentration is increased, the formation of cell aggregates is promoted. Most of these cancer cell aggregates have a spheroid-like morphology and reduced migratory capacity when the concentration of TGF-β in the microenvironment is lower. However, hi-gher concentrations of TGF-β induce the formation of strand-like clusters with a notably higher collective invasion capacity. This work shows that the concentration of the extracellular matrix is a key regulator of the generation of tumor aggregates, which affects their development and growth. It also exhibits how chemical factors can create a microenvironment that promotes the transformation of passive tumor aggregates into very active, invasive tumor structures. Finally, these results toge-ther demonstrate the relevant regulatory character of the mechano-chemical mi-croenvironment in conducting the preferential metastasis of tumor cells to specific
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tissues with high collagen concentrations and TFG-β activity.
References:[1] Kim, J., Feng, J., Jones, C. A. R., Mao, X., Sander, L.M., Levine, H., & Sun, Bo. Stress-induced plasticity of dynamic collagen networks. Nat Commun. 8, 842 (2017)[2] William, J., Zervantonakis, I. K., Roger, D. & Link, C. Tumor cell migration in com-plex microenvironments. Cell Mol Life Sci. 70, 1335–1356 (2015).[3] Shin, Y. et al. Microfluidic assay for simultaneous culture of multiple cell types on surfaces or within hydrogels. Nat Protoc. ; 7(7): 1247–1259 (2014)
Funding:European Research Council (ERC) through the INSILICO-CELL (ERC-2012-StG 306571) project, its proof of concept IMAGO (ERC-PoC-2016-737543) and the Spanish Ministry of Economy and Competitiveness through the project DPI2015-64221-C2-1-R.
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DEVELOPMENT OF PROGRAMMABLE PLANT TRANS-CRIPTIONAL ACTIVATORS BASED ON CRISPR /CAS9
Diego Martin, B.1, Selma García, S.2, Ajenjo Bauzá, M.3, Bernabé Orts, J.2, Orzáez Calatayud, D.2
1Student at the University of the Basque Country (EHU)1IBMCP Institute for Plant Molecular and Cellular Biology3Polytechnic University of Valencia (UPV)
The specific DNA recognition and binding capacity of the CRISPR/Cas9 system offers unprecedented possibilities in the field of Plant Synthetic Biology. Modifi-cations of Cas9 or its guide RNA allow the expansion of Cas9 activities, from the original nuclease function to other activities related to DNA binding, such as trans-criptional activation or repression. This opens the possibility of creating regulatory circuits that allow controlling genetic expression with greater precision. The aim of this work consists on the design and evaluation of new programmable transcriptio-nal activators based on the CRISPR/Cas9 system.In order to optimise the CRISPR/Cas9 system as a tool for transcriptional regula-tion a catalytically inactive version of the Cas9 endonuclease (dead Cas9 or dCas9) was used, to which a series of transcriptional activation domains were bound by two different strategies.One of the strategies, dCas9-SAM (Synergistic activation mediator) is based on the incorporation of aptamers to the gRNA scaffold, to which viral coat proteins fused to activator domains will bind. A second approach was dCas9-Suntag. This strategy consists on the addition of a C-terminal peptide, which contains several repeats of an epitope that is recognized by antibodies fused to transcriptional re-gulator domains.The study of transcriptional activation has been carried out in Nicotiana benthamia-na, targeting the dihydroflavonol reductase promoter of Solanum lycopersicum,
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which is a weak promoter, inducible by endogenous MYB-like transcriptional fac-tors. As a result of this study it was found that the dCas9-SAM strategy results in higher levels of expression, reaching increases in transcription rates of more than 20 fold as compared with the reference values of the non-activated promoter.
References:[1] Vazquez-Vilar, M. et al. A modular toolbox for gRNA-Cas9 genome engineering in plants based on the GoldenBraid standard. Plant Methods 12, 1–12 (2016).[2] Vazquez-Vilar, M. et al. GB3.0: a platform for plant bio-design that connects functional DNA elements with associated biological data. Nucleic Acids Res. 45, 2196–2209 (2017).[3] Dominguez, A. A., Lim, W. A. & Qi, L. S. Beyond editing: Repurposing CRIS-PR-Cas9 for precision genome regulation and interrogation. Nat. Rev. Mol. Cell Biol. 17, 5–15 (2016).[4] Tanenbaum, M. E., Gilbert, L. A., Qi, L. S., Weissman, J. S. & Vale, R. D. A pro-tein-tagging system for signal amplification in gene expression and fluorescence imaging. Cell 159, 635–646 (2014).
Funding:Design of synthetic orthogonal regulatory gene circuits in plants using CRIS-PR-Cas9-like programmable DNA-binding proteins. PI: Dr Diego Orzaez, Prof Anto-nio Granell Funding: Spanish Ministry of Economy and Competitiveness (BIO2016-78601-R). Co-financed by FEDER. Duration: 2017 - 2019
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PREDICTION OF STABILIZING POINT MUTATIONS IN PROTEIN STRUCTURES USING RATIONAL FEATURES IN
A MACHINE LEARNING WORKFLOWGarcía-Cebollada, H.1,2, Sancho Sanz, J.1,2,3
1University of Zaragoza, Biochemistry and Molecular and Cell Biology Department2Institute of Biocomputation and Physics of Complex Systems (Bifi)
3Aragon Health Research Institute (IIS Aragon), Universidad de Zaragoza, Spain
Increasing the stability of proteins is relevant for several applications, such as the production and storage of diagnostic kits and antibodies for therapeutic use or in-dustrial enzymatic catalysis for processes performed at high temperature [1, 2]. For this reason, several approaches have been developed to predict the effects of a mutation on protein stability. However, all of the currently available approaches are only capable of performing user-defined computational mutagenesis experiments. To solve this problem, reducing the number of mutations to analyse and, therefore, the output that the user has to process, we have developed a method based on simple rational and empirical rules that both proposes mutations and quantifies the probability of those mutations being stabilizing. Rules used in this program focus both on sequence analysis (ancestral and consensus sequences) and on struc-ture analysis, including composition of alpha helices, presence of disulphide and hydrogen bonds, exposure and burial of residues according to their polarity, steric clashes and internal cavities.Mutations are then evaluated with a logistic regression model trained using machi-ne learning techniques on a training group obtained from ProTherm database. As this database is dominated by destabilizing mutations with a negative free energy change upon mutation (∆∆G), we have made the assumption that ∆∆GA->B = ∆∆GB-
>A in order to obtain a symmetric database. The optimal parameters for fitting the model are evaluated using cross-validation to avoid overfitting. The accuracy of the final model is tested on common datasets, in order to compare
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its performance with some of the current alternatives for prediction of user-defi-ned mutations [3]. The program is run on 96 proteins with mutations present in ProTherm database, reaching a positive predictive value (PPV) of 70%, much hi-gher than randomly picking mutations from the database (PPV=18%). Our program shows a good performance that can be further improved with the development of more modules to study the structural properties of the proteins, such as electros-tatics [4].
References:[1] Zore, O. V., Pande, P., Okifo, O., Basu, A. K., Kasi, R.M., Kumar, C. V. RSC Adv. 7, 29563–29574 (2017).[2] Lamazares, E., Clemente, I., Bueno, M., Velázquez-Campoy, A. & Sancho, J. Sci. Rep. 5, 9129 (2015).[3] Pucci, F., Bernaerts, K., Kwasigroch, J. M. & Rooman, M. Bioinformatics (2018).[4] Estrada, J., Echenique, P. & Sancho, J. Phys. Chem. Chem. Phys. 17, 31044–31054 (2015).
Funding:FPU grant from the Spanish Government to Héctor García Cebollada
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CHARACTERIZATION OF PHOTOSWITCHABLE HYDRO-PHOBIC AND AMPHIPHILIC PEPTIDES FOR FOLDING
AND MEMBRANE INSERTION STUDIESGutiérrez-Salazar, M.V.1, Sampedro, D.2, Santamaría, E.2, Lórenz-Fonfría,
V.1
1Instituto de Ciencia Molecular, Universitat de València, España.2Centro de Investigación en Síntesis Química, Universidad de la Rioja, España.
Mechanics and kinetics of folding and insertion of hydrophobic and amphiphilic peptides in lipidic membranes is a process not fully understood. This is mainly due to the lack of sensitive experimental procedures that allow to follow the pro-cess with sufficient temporal and structural resolution. A practical approach to achieve this sensitivity is photocontrol of folding, using molecular photoswitches linked to the peptide. These photoswitches isomerize when irradiated with light of specific wavelengths, and can induce changes in the structure of the peptide, as folding or unfolding of the peptide and, consequently, modulate the insertion in the membrane. This work aims to characterize two model peptides (hydrophobic and amphiphilic) linked to a derivate of the molecular photoswitch azobenzene, by circular dichroism, infrared and ultraviolet/visible spectroscopies, to use them in fu-ture folding and membrane insertion studies. We designed different lighting setups to achieve photoisomerization with precision and in controlled environment. We characterized the azobenzene derivative (BCA) and concluded that it is a suitable candidate for photoswitching. The photoswitchable peptides were characterized in membrane-mimicking environments and solvents, to know in which conditions their structure could be controlled with photoswitching. The hydrophobic peptide showed good photoisomerization of BCA, but poor control of structure in most solvents. We managed to photocontrol the structure of the amphiphilic peptide in solvents, and some promising results were obtained in membrane environments.
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This work aims to be taken as a starting point for finding suitable photoswitchable membrane peptides.
References:[1] Gelman, H. & Gruebele, M. Fast protein folding kinetics. Q. Rev. Biophys. 47, 95–142 (2014). [2] Ulmschneider, J. P., Andersson, M. & Ulmschneider, M. B. Determining peptide partitioning properties via computer simulation. J. Membr. Biol. 239, 15–26 (2011). [3] Szymański, W., Beierle, J. M., Kistemaker, H. A. V, Velema, W. A. & Feringa, B. L. Reversible photocontrol of biological systems by the incorporation of molecular photoswitches. Chem. Rev. 113, 6114–6178 (2013). [4] Flint, D. G., Kumita, J. R., Smart, O. S. & Woolley, G. A. Using an azobenzene cross-linker to either increase or decrease peptide helix content upon Trans-to-cis photoisomerization. Chem. Biol. 9, 391–397 (2002).
Funding:BFU2016-76805-P, Ministerio de Economía, Industria y Competitividad
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BIOSYNTHESIS OF BETAXANTHINS BY ELICITATION WITH MEJA AND SA IN CELL CULTURES OF AMARAN-
THUS HYPOCHONDRIACUS VAR. NUTRISOLGuadarrama-Flores, B.1,2,3, Rodríguez-Monroy, M.2, Cruz-Sosa, F.1, Gar-
cía-Carmona, F.3, and Gandía-Herrero, F.3
1Departamento de Biotecnología, Universidad Autónoma Metropolitana Unidad Iztapala-pa, Col. Vicentina, México, D.F. (Mexico).1Departamento de Biotecnología, Centro de Desarrollo de Productos Bióticos (CeProBi), Instituto Politécnico Nacional, San Isidro, Yautepec, Morelos (Mexico).3Departamento de Bioquímica y Biología Molecular A, Unidad Docente de Biología, Facultad de Veterinaria. Regional Campus of International Excellence "Campus Mare Nostrum". Universidad de Murcia, Murcia (Spain).
Betalains are natural water-soluble pigments that contain nitrogen and provide a bright coloration to the fruits, flowers, leaves and roots of most Caryophyllales [1]. Betalains are divided into two groups: the red-violet betacyanins, with absorbance spectra centered at 536 nm, and the yellow-orange betaxanthins, with absorbance spectra centered at 480 nm. Both groups share betalamic acid as structural unit and chromophore, which is condensed with cyclo-DOPA in betacyanins and with amines and amino acids in betaxanthins [2]. Betalains are stable in acid medium and have antioxidant, anti-inflammatory, anticarcinogenic and neuroprotective ac-tivity in very low concentrations, recognizing them as nutraceutical substances, so they can be used as a natural bioactive dye [3]. In order to obtain cell cultures of Amaranthus hypochondriacus, var. nutrisol producing betalains, a stable line of greenish yellow callus was established in MS medium with BAP and 2,4-D, from which a cell line in suspension was derived. To induce the synthesis of betalains, callus lines and suspensions were elicited with 100 μM methyl jasmonate (MeJA) and 10 mM salicylic acid (SA). With this strategy, two dihydroxylated betalains were obtained: carboxylated dopaxanthin, miraxanthin V. Maximum accumulation of the pigments was reached in the suspension lines at 72 hours after adding MeJA.
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These cultures represent a suitable model for the study of activation in the betalains biosynthesis pathway, and can also be a viable source of pigments with possible industrial application.
References:[1] Miguel, M.G. Betalains in Some Species of the Amaranthaceae Family: A Re-view. Antioxidants (Basel). 2018, 7(4). pii: E53. doi: 10.3390/antiox7040053.[2] Casique-Arroyo, G.; Martínez-Gallardo, N.; González de la Vara L.; Délano-Frier, J.P. Betacyanin biosynthetic genes and enzymes are differentially induced by (a)biotic stress in Amaranthus hypochondriacus. PLoS One. 2014;9(6):e99012. doi: 10.1371/journal.pone.0099012.[3] Gandía-Herrero, F.; Escribano, J.; García-Carmona, F. Biological activities of plant pigments betalains. Crit. Rev. Food Sci. Nutr. 2016, 56, 937−945.
Funding:B.G.-F. holds a postdoctoral fellowship from “Consejo Nacional de Ciencia y Tec-nología” (CONACYT, Mexico)
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PRODUCTION OF PTEROSTILBENE IN METABOLICALLY ENGINEERED GRAPEVINE CELL CULTURES WITH ROSA
HYBRIDA ORCINOL O-METHYL TRANSFERASEMartínez-Márquez, A.1, Morante-Carriel, J.1,2, Palazon, J.3, Bru-Martínez,
R.1
1Plant Proteomics and Functional Genomics Group, Department of Agrochemistry and Biochemistry, Faculty of Science, University of Alicante, Alicante, Spain.2Biotechnology and Molecular Biology Group, Quevedo State Technical University, Que-vedo, Ecuador.3Laboratory of Plant Physiology, Faculty of Pharmacy, University of Barcelona, Av.Joan XXIII sn, E-08028 Barcelona, Spain
Stilbenes in grapevine are thought to play important roles in defence responses in several plant species. The main stilbenes in grapevine are resveratrol and its deri-vatives and, among these, pterostilbene (3',5'-dimethoxy-resveratrol; t-Pt) produ-ced in small amounts by an specific resveratrol O-methyltransferase (VvROMT) [1]. t-Pt has attracted much attention due both to its antifungal and pharmacological properties. Indeed, pterostilbene is 5 to 10 times more fungitoxic than resveratrol in vitro and recent studies have shown that pterostilbene exhibits anticancer, hypo-lipidemic, and antidiabetic properties. We demonstrated that grapevine cell cul-tures are able to accumulate more than 4 g/L of stilbenoid trans-resveratrol in the extracellular medium as end product when the culture is elicited with cyclodextins alone or combined with methyl jasmonate [2]. The combination of both cell culture elicitation and metabolic engineering strategies to produce resveratrol analogs pro-ved efficient for the dimethylated derivative pterostilbene, when grapevine O-me-thyltransferase VvROMT-transformed cell cultures were used [3]. Rose orcinol O-methyltransferase (RhOOMT) displays enzymatic properties, which makes it an appealing candidate to substitute VvROMT in the combined strategy to enhance the pterostilbene production level by engineered grapevine cells upon elicitation. We cloned a Rosa hybrida OOMT gene, and created a genetic construction suita-
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ble for Agrobacterium-mediated plant transformation. RhOOMT’s ability to catalyze the conversion of resveratrol into pterostilbene was first assessed in vitro using protein extracts of agroinfiltrated Nicotiana benthamiana leaves and transformed grapevine callus. The grapevine cell cultures transformed with RhOOMT produced about 16 mg/L culture of pterostilbene and reached an extracellular distribution of up to 34% of total production at the best, which is by far the highest produc-tion reported to date in a plant system. A bonus large resveratrol production of ca. 1500–3000mg/L was simultaneously obtained. As a conclusion, these results demonstrate a viable successful metabolic engineering strategy to produce pteros-tilbene, a resveratrol analog with enhanced pharmacological properties.
References:[1] Schmidlin L, Poutaraud A, Claudel P, Mestre P, Prado E, et al. A stress-inducible resveratrol O-methyltransferase involved in the biosynthesis of pterostilbene in gra-pevine. Plant Physiol 2008;148:1630–1639.[2] Almagro L, Belchí-Navarro S, Sabater-Jara AB, Vera-Urbina JC, Selles-Mar-chart S, et al. Bioproduction of trans-resveratrol from grapevine cell cultures. In: Ramawat KG, Merillon JM, editors. Handbook of Natural Products. Heidelberg: Springer; 2013. p. 1683–1713. [3] Martínez-Márquez A, Morante-Carriel JA, Ramírez-Estrada K, Cusidó RM, Pala-zon J, Bru-Martínez R. Production of highly bioactive resveratrol analogues pteros-tilbene and piceatannol in metabolically engineered grapevine cell cultures. Plant Biotechnol J 2016;14:1813–1825.
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IN SILICO BINDING SITE DETECTION IN ABCC3 FOR PHARMACOPHORE-BASED DRUG DESIGN
Ruiz-López E.
1Aragon Health Research Institute (IIS ARAGON), Molecular Oncology Group, Zaragoza, Spain.
ATP Binding Cassette family C member 3 (ABCC3) is a multispecific organic anion transporter associated with ATP-dependent efflux of drugs. ABCC3 overexpres-sion in cancer cells confers resistance to multiple structurally unrelated chemo-therapeutic agents, leading to multidrug resistance (MDR) phenotypes [1]. One successful therapeutic option in sensitizing MDR cancer cells against conventio-nal chemotherapy has been the co-administration of repositioned drugs targeting ABCC3. Tyrosine kinase inhibitors, cannabinoid type 1 receptor antagonists, and reverse transcriptase inhibitors have been shown to directly reduce ABCC3 trans-port activity. Nevertheless, there are no specific ABCC3 inhibitors ready for clinical use. While some novel specific ABCC3 inhibitors have been recently identified by virtual screening using Bayesian models, they have not been tested nor achieved success in clinical trials yet [2]. Due to the absence of a human ABCC3 experimentally determined structure, we developed a three-dimensional model of ABCC3 by using structure prediction bioinformatic software. We perform molecular docking assays of different non-spe-cific inhibitors [3, 4], to find out presumable surface pockets on the protein and detect potential binding sites. This binding sites can then be used for designing pharmacophore-based specific drugs. ABCC3 rationally designed drugs will allow a pharmacological control of ABCC3 transport activity not only by themselves but also by complementing immuno-targeting strategies against this protein target. Im-munotherapy treatment of MDR cancer cells with mAb against ABCC3 in combina-
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tion with specific ABCC3 transport activity inhibitors may decrease synergistically cancer progression.
References:[1] König, J., et al., 2005. Expression and localization of human multidrug resistance protein (ABCC) family members in pancreatic carcinoma. International journal of cancer, 115(3), 359-367.[2] Ali, I., et al., 2017. Identification of novel MRP3 inhibitors based on computa-tional models and validation using an in vitro membrane vesicle assay. European Journal of Pharmaceutical Sciences, 103, 52-59.[3] Beretta, G. L., et al., 2017. Overcoming ABC transporter-mediated multidrug resistance: the dual role of tyrosine kinase inhibitors as multitargeting agents. Euro-pean journal of medicinal chemistry.[4] Wittgen, H. G., et al., 2011. Cannabinoid type 1 receptor antagonists modulate transport activity of multidrug resistance-associated proteins MRP1, MRP2, MRP3, and MRP4. Drug Metabolism and Disposition, 39(7), 1294-1302.
Funding:PhD grant from the Spanish Association Against Cancer, AECC
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MYCO-MIGE: OPTIMIZATION OF A NEW POWERFUL TOOL FOR MYCOBACTERIAL GENOME ENGINEERING
Calvet, J.1; Campos-Pardos, E.1; Ainsa, J.A.1,2,3; Martín, C.1,2; Gonza-lo-Asensio, J.1,2,3
1Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain1CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain3Institute for Biocomputation and Phisics of Complex Systems (BIFI), Universidad de Zaragoza, Zaragoza, Spain.
In 2009, Multiplex Automated Genome Engineering (MAGE) was described as a new powerful tool to introduce multiple mutations in Escherichia coli, using a cy-clic automated system. MAGE uses the recombineering machinery to introduce ssDNA oligonucleotides (oligos) with the desired mutations [1]. More recently, this technique has been improved following a co-selection strategy, in which, an oligo carrying an antibiotic resistant genotype is added together with the oligos carrying the desired mutations [2].With the objective to implement this technique in mycobacteria, we propose the project Myco-MIGE. Unlike MAGE, in this project we manually performed the au-tomation process in an iterative manner following several transformation cycles. Mycobacterium smegmatis mc2155 carrying the recombineering system in the plasmid pJV53 is used as a reliable surrogate host to demonstrate proof-of-con-cept of this methodology. In a first step of Myco-MIGE, we optimized the length and concentration of the mutagenic oligos. Oligos carrying a SNP that confers streptomycin resistance were designed to replace the wild type allele of the rpsL gene (which confer sensibility to streptomycin), thus providing a selectable phenotype. In a next step, we designed oligos to inactivate fourteen efflux pumps in M. smegmatis, by placing two conse-cutive STOP codons (missense mutations) in frame with the corresponding gene in
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the 5’ end of the coding sequence. All these oligos were transformed in M. smeg-matis together with the oligo conferring streptomycin resistance in a 100:1 ratio, in order to allow isolation of resistant bacteria and follow a co-selection strategy.Using the Mismatch Amplification Mutation Assay PCR and Real Time MAMA PCR, we have demonstrated that higher percentages of the desired mutations ac-cumulate in the bacterial population throughout the Myco-MIGE cycles and these mutations are more abundant in the streptomycin resistant population. Altogether, this tool hold promise to improve and accelerate multiplex genome engineering in the Mycobacterium genus opening new research avenues.
References:[1] Wang et al. Programming cells by multiplex genome engineering and accelera-ted evolution. Nature (2009).[2] Carr PA, et al. Enhanced Multiplex Genome Engineering through Cooperative Oligonucleotide Co-selection. Nucleic Acids (2012)
Funding:BFU2015-72190-EXP
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INHIBITION OF HIF-1a/BNIP3 AXIS AND HYPOXIA-MEDIATED MITO-
PHAGY BY MELATONIN ADDITION ENHANCES HUMAN HEPATOCELLU-
LAR CARCINOMA CELLS SENSITIVITY TO SORAFENIB TREATMENT
Fondevila, F.1,2, Méndez-Blanco, C.1,2, Prieto-Domínguez, N.1,2, Fernán-dez-Palanca, P.1,2, García-Palomo, A.3, González-Gallego, J.1,2, Mauriz,
J.L.1,2
1Institute of Biomedicine (IBIOMED), University of León, León, Spain2Centro de investigación biomédica en red de enfermedades hepáticas y digestivas (CI-BERehd), ISCIII, Madrid, Spain 3Medical Oncology Service, Complejo Asistencial Universitario de León, Hospital of León, León, Spain.
Background: sorafenib is the only drug approved as first-line treatment for advan-ced hepatocellular carcinoma (HCC), but its efficacy is limited due to the develop-ment of resistant tumor cells. Overexpression of hypoxia-inducible factor 1 alpha (HIF-1α) is related to sorafenib acquired resistance in advanced HCC. The HIF-1α target B-cell lymphoma-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) is the master regulator of hypoxia-induced mitophagy in liver, a process which exhi-bits a dual role in cancer favoring cell survival or death depending on the cellular context. Melatonin has shown oncostatic, proapoptotic, antiangiogenic and anti-metastatic properties on HCC cells.Aim: our aim was to evaluate the melatonin ability to enhance the sensitivity of HCC cells to sorafenib, focusing on the modulation of HIF-1α-induced mitophagy.Methods: Hep3B human HCC cells were treated with the hypoximimetic CoCl2 (100 µM), sorafenib (5 µM) and melatonin (2 mM). siRNAs were employed to silence HIF-1α and BNIP3 genes; cell viability was analyzed by MTT assay; hypoxia, mito-phagy and apoptosis-related proteins levels were measured by Western blot; mito-chondria and lysosomes colocalization was assayed using immunofluorescence, laser confocal imaging and ImageJ software; and GraphPad Prism 6 software was employed to perform the statistical analysis, considering significant differences
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when p<0.05.Results: coadministration of melatonin and sorafenib strongly reduced the hypoxia-induced accumulation of HIF-1α and its mitophagy target BNIP3. BNIP3 downregulation resulted in a significant reduction of cell viability, suggesting a cyto-protective role of mitophagy in our HCC in vitro model. Melatonin addition was able to abolish HIF-1α-induced mitophagy and enhance apoptotic cell death through the inhibition of HIF-1α/BNIP3 axis, thus improving sorafenib efficacy.Conclusion: these results suggest that melatonin can efficiently suppress the pro-survival HIF-1α-induced mitophagy, becoming a potential coadjuvant for the che-motherapeutic treatment of HCC.
Funding:CIBERehd is funded by Instituto de Salud Carlos III. FF and NPD are supported by the Ministry of Education of Spain (Becas FPU: FPU16/05277 and FPU13/04173, respectively), CMB by the Asociación Española Contra el Cáncer (AECC)-Junta provincial de León, and PFP by the IBIOMED-University of León.
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BIBLIOGRAPHIC REVIEW OF CELLULAR DIFFERENTIATION OF OMMATIDIUM IN DROSOPHILA MELANOGASTER
González-García, P., Bellido-Gutiérrez, J.M.
Universidad de Cádiz (UCA).
Drosophila melanogaster has been of special importance for understanding human embryogenesis at genetic and molecular level, due to the notable similarities be-tween their genome and ours (and, in this case, their development mechanisms), the amount of knowledge there is about this species, and many other reasons that make the Drosophila melanogaster an excellent model organism. In particular, cell signalling pathways involved in cell and tissue differentiation studied in said organism have shed light on biochemical mechanisms responsible for human em-bryonic development. With this bibliographic review, we intend to show the diffe-rent signalling pathways involved in the formation of the compound eyes (and, therefore, of the ommatidia they are made of) of the dipteran during its embryoge-nesis. The most important pathways in this process are mainly three, all of them related with transmembrane receptors. The first of them is Spitz/DER, in which the ligand, Spitz, is secreted by adjacent cells to a precursor cell. This cell con-tains a transmembrane protein called DER, with intrinsic tyrosine kinase activity, which promotes differentiation. A second pathway of special interest is the Boss/Sev (Bridge of Sevenless/Sevenless), which is activated when a transmembrane proteic ligand (Boss), situated in the precursor cell’s membrane, causes conforma-tional changes in Sevenless, a Receptor Tyrosine Kinase (RTK) on the membrane of another precursor cell, which then goes through the differentiation process. And the third pathway is the Notch/Delta. The same way as in Spitz/DER, both Notch and Delta are transmembrane proteins located in adjacent cells. In this case, the signalling pathway starts with several proteolytic cleavages. In essence, all these
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pathways coordinate to promote the development of the ommatidium. Finally, we will highlight some of the genes that codify the main pigments that give Drosophila melanogaster’s compound eyes their characteristic red coloration. Likewise, we will show the consequences that mutations in these loci can have, and how this causes vastly different colours in the pigmentary cells of the ommatidia.
References:[1] Kuman, J.P. (2012). Building an ommatidium one cell at a time. Dev Dyn. 241, 136–149.[2] Ben-Zion, S. (2003). Signaling by the Drosophila epidermal growth factor recep-tor pathway during development. Cell Research. 284, 140–149.[3] Matthew, F. (1996). Reiterative use of the EGF receptor triggers differentiation of all cell types in the Drosophila eye. Cell Press. 87, 651–660.[4] Baonza, A.; Matthew, F. (2001). Notch signalling and the initiation of neural deve-lopment in the Drosophila eye. Development. 128, 3889-3898.)
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THE ROLE OF FURC IN THE RESPONSE OF ANABAENA PCC7120 TO OXIDATIVE STRESS
Nevot, G., Sarasa, C., González, A., Peleato, M.L., Fillat, M.F. and Sevilla, E.
Department of Biochemistry and Molecular and Cell Biology and Institute for Biocom-putation and Physics of Complex Systems. Faculty of Sciences, University of Zaragoza, Pedro Cerbuna 12, 50009-Zaragoza, Spain.Fur proteins are a widespread family of transcriptional regulators present in a broad range of bacteria, some of them responsible for pathogenicity. In the cyanobacteria Anabaena PCC7120, three paralogs of this family have been identified as FurA, FurB and FurC. Whereas FurA and FurB have defined roles as iron and zinc regula-tors, the function of FurC remains unclear. Previous research in our group revealed that FurC was unable to bind any of the three fur promoters. Nevertheless, FurC was shown to modulate FurA and FurB autoregulation in vitro, intensifying DNA binding of the former and inhibiting the latter [1]. Recently, the strong induction of FurC expression under oxidative stress conditions and its action mechanism has led to purpose it as the hydrogen peroxide regulator (PerR) of Anabaena PCC7120 [2]. In the present study, we have analysed the effects of FurC-overexpression in the phenotype and transcriptional profile of Anabaena PCC7120 to provide further insights in FurC regulation. Interestingly, the high levels of FurC led to more sensi-tivity to oxidative stress produced either by hydrogen peroxide or methyl viologen. Additional biochemical assays showed a reduction of superoxide dismutase and catalase activities among other physiological alterations. In order to assess the behaviour of the strain under oxidative stress, the expression of key genes involved in this response was determined. Our data revealed an impairment of the expres-sion pattern under oxidative conditions in the genes sodA (superoxide dismutase), alr0998 (Mn-catalase) and prxA (peroxiredoxin), suggesting that FurC might directly or indirectly regulate them. To prove this, EMSA analysis were performed with FurC
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protein and prxA, sodA and alr0998 promoters showing FurC ability to bind only to prxA promoter. However, FurB protein was previously described in our laboratory to bind alr0998 and sodA promoters, regulating their transcription. In this context, we repeated EMSA assays incubating FurB and FurC together and the results su-ggested an undescribed regulatory mechanism involving these two proteins that could indicate a crosstalk between oxidative stress and zinc homeostasis. Taken together, our results reveal that the role of FurC in oxidative stress response is more complex than it was previously expected.
References:[1] Hernández JA, López-Gomollón S, Bes MT, Fillat MF, Peleato ML. Three fur homologues from Anabaena sp. PCC7120: exploring reciprocal protein-promoter recognition. FEMS Microbiol Lett. 2004 Jul 1;236(2):275–82. [2] Yingping F, Lemeille S, Talla E, Janicki A, Denis Y, Zhang C-C, et al. Unravelling the cross-talk between iron starvation and oxidative stress responses highlights the key role of PerR (alr0957) in peroxide signalling in the cyanobacterium Nostoc PCC 7120. Environ Microbiol Rep. 2014 Oct;6(5):468–75.
Funding:BFU2016-77671-P
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UNC0642 EPIGENETICALLY ACTIVATES AUTOPHAGY AND MODULATES THE CELLULAR CHARACTERISTICS
AND SURVIVAL OF U2OS CELLSRodriguez-Pastrana, I. and Coutts, A.S.
NOTTINGHAM TRENT UNIVERSITY - COLLEGE OF SCIENCE AND TECHNOLOGY.
Autophagy is a catabolic process that degrades different cytoplasmic components and damaged-organelles in order to allow the cells to reuse their basic biomo-lecules. Autophagy is a cellular intrinsic pathway that maintains the tissue ho-meostasis, but it can easily be activated by different stress stimuli like starvation or chemotherapeutic-drugs, acquiring a cell survival role. UNC0642 is an epigene-tic G9a-methyltransferase inhibitor, which reduces the methylation levels of H3K9 (histone-3/lysine-9). We show that, the presence of UNC0642 produces cellular density and morphological changes with concentrations greater than 1μM-dose during 48 hours of exposure, with a possible senescence induction. Furthermo-re, we report that UNC0642 presents low toxicity levels being the first epigenetic G9a-methyltransferase inhibitor to be tested in vivo. We also show that, UNC0642 rises in a time and concentration-dependent manner the autophagy process. This autophagy induction is demonstrated by an increase in the transformation of LC3-I into LC3-II, a reduction of the cytoplasmic p62 levels and the accumulation of fluo-rescence autophagosomes. Thus, our results establish that UNC0642 is a potent epigenetic regulator, with low cytotoxicity and it can induce autophagy in osteosar-coma cells (U2OS).
References:[1] Liu, F. et al. Discovery of an in vivo chemical probe of the lysine methyltransfera-ses G9a and GLP. J. Med. Chem. 56, 8931–8942 (2013).[2] Sui, X. et al. Epigenetic modifications as regulatory elements of autophagy in
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cancer. Cancer Lett. 360, 106–113 (2015) [3] Choi, A. M. K., Ryter, S. W. & Levine, B. Autophagy in human health and disease. N. Engl. J. Med. 368, 651–662 (2013).[4] Coutts, A. S. & La Thangue, N. B. Regulation of actin nucleation and autophago-some formation. Cell. Mol. Life Sci. 73, 3249–3263 (2016).
Funding:NOTTINGHAM TRENT UNIVERSITY - COLLEGE OF SCIENCE AND TECHNOLO-GY. Dr. AMANDA S. COUTTS
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CHARACTERIZATION OF KLEBSIELLA PNEUMONIAE BACTE-RIOPHAGES WITH BIOTECHNOLOGICAL POTENTIAL
Torres, B.1, Shorff, S.3, Koskinen, K.2, Penttinen, R.2, Jalasvuori, M.2
1University of Zaragoza, Spain.2Department of Biological and Environmental Science, Nanoscience Center, University of Jyvaskyla, Finland.3University of Jyvaskyla, Finland
Klebsiella pneumoniae has emerged as the major cause of hospital-acquired infec-tions. The extensive use and misuse of antibiotics has led to an increased emer-gence of multidrug-resistant Klebsiella pneumoniae strains, which are a serious concern worldwide since they have a great propensity to spread and a small num-ber of effective treatments are left [1]. Consequently, phage therapy is garnering renewed interest as an alternative method to defeat antibiotic resistant bacteria. Alongside this, phages – natural pathogens of bacteria – have several properties, such as high capacity to replicate as long as the host is present and high host spe-cificity that turns them into a great advantage in the face of antibiotics [2]. In this study, eight bacteriophages were characterized according to their genetic material and morphology by performing endonuclease digestions and transmis-sion electron microscopy imaging with 1% phosphotungstic acid or 2% uranyl acetate as staining dyes. Then, they were classified in agreement with their mor-phological characterization. Seven phages were classified into Siphoviridae family (EKP3P1, EKP3P2, EK-P3P4, EKP3P5, EKP8P2, EKP8P3, EKP8P4) showing hexagonal heads with long non-contractile, sometimes flexible, tails and closely related restriction patterns among them. EKP8P1 phage was classified into Podoviridae family showing an icosahedral head with a short non-contractile tail and a different restriction pattern.
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All of them belong to Caudovirales order. In addition, a prophage was found in EK-P8P1 sample, and classified into Siphoviridae family according to its morphology. The genome of EKP3P5 phage, a double stranded DNA of 47,622 bp long, was sequenced and, then, manually annotated. EKP3P5 phage turned out to be a tem-perate phage encoding integrase, holin and endolysin proteins, among others. As a temperate phage, EKP3P5 could not be used in phage therapy due to the risk of transferring virulence and resistance genes to the host bacteria, turning it into a more pathogenic strain and contributing in antibiotic resistance dissemination.For all the above reasons, this study provides detailed knowledge of the physical structure along with genomic qualities of eight multidrug-resistant Klebsiella pneu-moniae infective bacteriophages. This is important for determining the potential of phages as therapeutic agents and the first step to improve phage therapy.
References:[1] Antimicrobial resistance: global report on surveillance. (World Health Organiza-tion, 2014).[2] Matsuzaki, S. et al. Bacteriophage therapy: a revitalized therapy against bacterial infectious diseases. J. Infect. Chemother. 11, 211–219 (2005).
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MULTI-STABILITY OF BLOOD CIRCULATION IN LAD-DER-SHAPED NETWORKS
De-Vicente-Martínez, B., Podgorski, T., and Coupier, G.
Laboratoire Interdisciplinaire de Physique (LIPhy) UMR5588 CNRS-Université Grenoble Alpes, Grenoble F-38041, France
All human cells need oxygen supply as well as carbon dioxide removal and red blood cells (RBCs) are in charge of those functions. To make that possible, blood flows through a complex network of the circulatory system, from large arteries to very tiny capillaries where RBCs accomplish their vital functions. It is worthy to note that RBCs do not behave as passive tracers, as their size is comparable to that of blood capillaries. RBCs flexibility and dynamics have a decisive role in the haematocrit partition at the level of bifurcations, which is the main mechanism that dictates blood heterogeneity in the microvascular networks, and it affecting many physiological functions, although it remains poorly understood. Therefore, in or-der to have a better insight of some causes and consequences related to circula-tory pathologies, it would be interesting to study the parameters that influence the partition of haematocrit at the microvascular bifurcations, to improve and lead to new applications in biomedical technology, for example in blood substitute deve-lopment and transfusion techniques. Previous computer simulations, consisting in numerical resolution of the system of equations governing the flow in ladder-sha-ped networks using specific models for blood rheology and phase separation, pre-dict interesting and non-intuitively multi-stability states for the velocity profile and haematocrit partition in ladder-shaped microchannels. In this study, we mimicked human capillaries utilizing microfluidic chips and studied the soundness or not of those simulations. For that, we carried out blood flow experiments through 2-rung ladder-shaped microchannels. The results prove the existence of different states and at least two branches of stable solutions in the 2-rung ladder-shaped network.
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Furthermore, both show the tendency to be maintained in those branches, but also an oscillatory behaviour in time. Related with the precedent in silico solutions, we prove the main characteristic of multiple-stability states, but the shape of the solu-tions discerns. This work has been the first experimental characterisation of multi-stability for blood flow in channel networks and a preliminary approach to RBCs suspensions behaviour in a basic model of capillary beds, which opens the door to new studies in the area.
References:[1] Pries, A. R., Neuhaus, D., Gaehtgens, P., 1992. Blood viscosity in tube flow: dependence on diameter and hematocrit. The American Physiological Society 363, 6135-6192[2] Shen, Z., Coupier, G., Kaoui, B., Polack, B., Harting, J., Misbah, C., Podgorski, T., 2016. Inversion of hematocrit partition at microfluidic bifurcations. Microvascular Research 105, 40-46.
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SYNTHESIS AND EVALUATION OF THE BIOLOGICAL ACTIVITY OF LIPOPEPTIDES DERIVED FROM BP100
CONTAINING A D-AMINO ACID
Moll, L.1, Oliveras, A.1, Feliu, L.1, Planas, M.1, Badosa E.2, Montesinos, E.2
1LIPPSO, Department of Chemistry, University of Girona, Campus Montilivi, Girona,2Laboratory of Plant Pathology, Institute of Food and Agricultural Technology-CID-SAV-XaRTA, University of Girona, Campus Montilivi, Girona.
Nowadays, world population has reached 7,6 billion and it is expected to rise up to 11,2 billion in 2100. This increase requires to step up the agricultural yield in order to supply food for the whole population. A way to achieve this purpose would be reducing the losses caused by microorganisms [1]. Recent restrictions imposed by the European Union on the use of several compounds to combat these pathogens, has prompted the search for safer alternatives. Antimicrobial peptides are conside-red as optimal candidates. Some years ago, our group, in collaboration with the Laboratory of Plant Pathology, described the lead peptide KKLFKKILKYL-NH2 (BP100) with antimicrobial activity against economically important plant pathogens [2]. More recently, with the aim of obtaining peptides with better biological properties, several lipopeptides have been synthetized. This type of peptides contain a fatty acid in their structure to fa-vour their insertion into the pathogen membrane [3]. The lipopeptides derived from BP100 displayed high antimicrobial activity, but they were hemolytic and poorly stable. In this work, in order to enhance the properties of the above BP100 derivatives, new lipopeptides have been described. In particular, the amino acid at position 4 has been replaced by its D enantiomer. This approach has been designed to redu-ce the hemolysis and to increase the stability, while maintaining the antimicrobial activity [4]. These new lipopeptides have been prepared on solid phase. They have
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been analysed by HPLC and characterized by ESI-MS. They have been tested against the phytopathogenic bacteria Erwinia amylovora, Pseudomonas syringae pv. syringae, Pseudomonas syringae pv. actinidiae, Xanthomonas arboricola pv. pruni, Xanthomonas fragariae, Xantomonas axonopodis pv. vesicatoria, and the fungi Penicillium expansum and Fusarium oxysporum. Furthermore, the toxicity and the stability have been analysed. The best lipopeptides will be selected to be assayed in vivo and, if they are successful, they will be produced in plants to de-crease the production cost.
References:[1] S. Savary, A. Ficke, J.N. Aubertot, C. Hollier. Crop Losses Due to Diseases and Their Implications for Global Food Production Losses and Food security. Food Se-cur. 2012, 4, 519-537. [2] E. Badosa, R. Ferre, M. Planas, L. Feliu, E. Besalú, J. Cabrefiga, E. Bardají, E. Montesinos. A Library of Linear Undecapeptides with Bactericidal Activity against Phytopathogenic Bacteria. Peptides. 2007, 28, 2276-2285. [3] A. Malina, Y. Shai. Conjugation of Fatty Acids with Different Lengths Modulates the Antibacterial and Antifungal Activity of a Cationic Biologically Inactive Peptide. Biochem. J. 2005, 390, 695-702. [4] I. Guell, J. Cabrefiga, E. Badosa, R. Ferre, M. Talleda, E. Bardaji, M. Planas, L. Feliu, E. Montesinos. Improvement of the Efficacy of Linear Undecapeptides against Plant-Pathogenic Bacteria by Incorporation of D-Amino Acids. Appl. Envi-ron. Microbiol. 2011, 77, 2667-2675.
Funding:MINECO, Grant AGL2015-69876-C2-2-R; University of Girona, MPCUdG2016/038
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SEMINAL PLASMA FROM BOARS WITH HIGH RESISTANCE TO COLD SHOCK COULD IMPROVE POST-THAWING SPERM
QUALITY
Núñez-González, A.1, Crespo-Félez, I.1,2, Fernández-Alegre, E.1,2, Nadri, T.3, Martínez-Pastor, F.1,2,4, González-Urdiales, R.1,5
1INDEGSAL, León, Spain. 2Grupo IMAPOR, León, Spain. 3Dept. of Animal Science, College of Agriculture and Natural Resources, University of Tehran, Karaj, Iran. 4Dept. of Molecular Biology, Universidad de León, León, Spain.5Grupo Topigs Ibérica (AIM Ibérica), León, Spain
Swine industry depends on the generation of seminal doses of selected boars and their application by artificial insemination, which is mainly carried out by using refri-gerated semen. As boar spermatozoa are particularly sensitive to cryopreservation, frozen doses still produce variable results. When sperm is cold-shocked by rapid cooling, the resulting injuries do not present the same intensity in every animal. This variability may be due not only to intrinsic differences in the sperm membranes but also to the action of external factors such as seminal plasma (SP). It is well-known that quantitative differences in specific SP components exist between sires. Hence, the protein composition of SP could explain differences between boars regarding the ability of their sperm to sustain cryopreservation. This study aimed to evaluate the effects of boar SP on membrane integrity, acrosomal status, mitochondrial ac-tivity and capacitation of spermatozoa after thawing, presuming that its effective-ness depends on the male from which it is obtained. We proposed that SP derived from males whose semen is resistant to cold shock could be the most suitable for its application as a protector. Thus, this study was conducted to compare the SP of males producing semen with different resistance to cold shock, in terms of its effectiveness in maintaining the quality of thawed sperm. Our work evidenced that the addition of 20 % (v/v) SP arising from cold shock-resistant boars increases
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post-thaw motility relative to non-supplemented sperm (p<0.001). Remarkably, this effect was not evident when using SP from boars whose semen was classified as susceptible to cold shock. Besides, supplementation with SP, regardless its origin, had some detrimental effects on spermatozoa (increased apoptosis rate, capa-citation status and acrosomal damage), but it improved (p<0.05) sperm viability after thawing relative to control sperm. Our results show that the addition of SP to frozen-thawed seminal doses induces changes in sperm physiology, presumably through the interaction of plasma proteins with the sperm membrane. Those chan-ges are more desirable when SP comes from males classified as highly-resistant, evidencing that cold shock could be a useful tool when selecting boars from which SP should be obtained.
References:[1] González Urdiales, R. (2011) Valoración de la capacidad de criopreservación espermática del semen porcino mediante técnicas de choque a frigore y termorre-sistencia. University of León. Available at: http://hdl.handle.net/10612/843.
Funding:This work has been supported by project CEI15-24 (Ministry of Education, Culture and Sport, Spain), through Campus of International Excellence of the University of Oviedo. The authors thank Topigs-Norsvin Ibérica (León, Spain) for housing the animals and providing the semen samples.
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IDENTIFICATION OF NOVEL TARGETS FOR ANTI-PSEUDOMONAS AEURGINOSA THERAPIES
Txopitea-Elorriaga, M.
University of the Basque Country UPV EHU
Pseudomonas aeruginosa infections are becoming more difficult to treat since the available antibiotics have significant limitations while the development of new an-timicrobials has slowed down; all attempts to obtain a vaccine have failed to date. Severe infections like necrotizing pneumonia or sepsis have already a high mortali-ty rate, even if treated with the right combination of antimicrobials. In this study, we investigated how low physiological conditions affect bacterial viru-lence and their ability to communicate and cooperate. For many bacteria, coope-rative virulence is achieved through communication via complex 'quorum sensing' (QS) networks. QS is important for ‘successful’ virulence, as it requires coordinated production of virulence factor to overcome host defences. We were interested in the interplay of QS, virulence and physiology in P. aeruginosa. To achieve its high degree of pathogenicity, the bacterium makes use of its impressive arsenal of viru-lence factors, including for example the redox-active pigment pyocyanin, several type of protein secretions systems and host defense-targeting enzymes like elas-tase. Regulation of many of these virulence factors by QS ensures a high degree of synchronisation and thus efficiency.To address this question, we have grown P. aeruginosa in 96 different conditions (71 single carbon sources, 23 ‘stressor’ conditions and two controls) in BIOLOG GenIII plates and additionally compared differences between mutants affected in metabolic regulators. To characterise pleiotropic effects and dynamics, we quanti-fied the levels of compounds of all four QS systems in P. aeruginosa (butyl-homo-serine lactone, 3-oxo-dodecanyl-homoserine lactone, the Pseudomonas quinolo-
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ne signal (PQS) family and iQS) targeted LC/MS methods. We further assayed for the virulence factors pyocyanin. We found that QS compound production is highly context-dependent and partially uncoupled from cellular density. For example, a supposed ‘stressor’ condition, low pH led to elevated PQS and pyocyanin level, while high salt significant lowered pyocyanin production.Overall, the experiments led to interesting insights into the impact of environmental conditions on P. aeruginosa virulence and have the potential to open up avenues for targeting pathway to silence QS production via physiological means.
References:[1] Behrends, V., Bell, T. J., Liebeke, M., Cordes-Blauert, A., Ashraf, S. N., Nair, C., Bundy, J. G. (2013). Metabolite Profiling to Characterize Disease-related Bac-teria. Journal of Biological Chemistry, 288(21), 15098-15109. doi:10.1074/jbc.m112.442814[2] Linares, J. F., Moreno, R., Fajardo, A., Martínez-Solano, L., Escalante, R., Rojo, F., & Martínez, J. L. (2010). The global regulator Crc modulates metabolism, sus-ceptibility to antibiotics and virulence in Pseudomonas aeruginosa. Environmental Microbiology, 12(12), 3196-3212. doi:10.1111/j.1462-2920.2010. 02292.x[3] Martínez, J. L., & Rojo, F. (2011). Metabolic regulation of antibiotic resistan-ce. FEMS Microbiology Reviews, 35(5), 768-789. doi:10.1111/j.1574-6976.2011. 00282.x.
Funding:Faro internship: FUNGE (Fundacion General University de Valladolid) Spain Ministry of Education through the Secretary of State for Education, Vocational Training and Universities.
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Cursos de formación
En las diferentes ediciones del congreso se han realizado diversos cursos. En BAC2018 se pro-ponen el curso de fecundación in vitro, que ha tenido una muy buena acogida en las dos pa-sadas ediciones, un curso de Design Thinking y otro de Bioinformática.
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Design ThinkingInnovar es clave para diferenciarse de la com-petencia, ya sea en biotecnología o en cual-quier otra rama profesional. Para conseguirlo, existen metodologías como el Design Thin-king, pero ¿en qué consiste exactamente?La detección de necesidades aún no satisfe-chas en un mundo lleno de oportunidades es un arte, algo que todos podemos aprender pero no sin esfuerzo y voluntad.
BioinformáticaLa bioinformática es un área emergente inter-disciplinaria que se ocupa de la aplicación de la informática al tratamiento de información relativa a datos biológicos o médicos. Se tra-ta de una ciencia estratégica e imprescindible actualmente, para dar sentido a la avalancha de datos biológicos que se pueden obtener en espacios temporales cortos.El curso de bioinformática se dividirá en tres partes, una parte teórica, en la que se tratará la evolución de la Biología de Sistemas y sus aplicaciones más relevantes en la biomedici-na.
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11 de julio de 2018De 10h a 14h.
11 de julio de 2018De 11h a 13h.
Cursos de formación
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Taller de desarrollo personal y profesional
Preparación para la búsqueda de empleo: RRJJ (organigrama, funciones), elaboración de CV, elaboración de carta de presentación.Entrevista de trabajoDesarrollo de habilidades interpersonales y competencias.
Seminario Gestión de proyectosImpartido por IUCT.
Definición de proyecto científico: conceptos y ob-jetivosGestión del proceso de innovación
12 de julio de 2018De 16h a 17:30h.
12 de julio de 2018De 16h a 17:30h.
Cursos de formación
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Programa Social
Jueves 12 de julio
Ruta turística
Ruta por el casco antiguo de Girona, por sus rincones más característicos y por las calles donde se rodó la serie Juego de Tronos. Shame!
Cuándo: Miércoles 11 de julio a las 19.15h2 grupos de 25 personas
Ruta de tapas
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Inicio: Facultad de Letras de Giro-na (sede del Congreso)
Finalización: Plaza Catalunya
Ruta de tapas por la ciudad de Girona. Entra en contacto con la genial gastro-nomía de la ciudad.
Programa Social
Viernes 14 de julio
Biotechnoparty
La Biotechnoparty es uno de los elementos de encuentro social más ca-racterístico y rememorado de los BAC. Consiste en una fiesta con temática Biotec con juegos, sorpresas y mucha música.
Jueves noche, 4 cervezas o 2 copas. Mientras tanto, la ya immortal fiesta de BAC, ahora con karaoke.
Lugar: Bar Celtic (Carrer del Riu Güell, 1, 17001 Girona)
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Programa Social
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Visitas
Este año se plantea organizar una visita a la Fuente de Luz de Sincrotrón Alba de
Barcelona. En esta visita científica podrás conocer de primera mano el funciona-
miento e instalaciones del sincrotrón así como relacionarte con otros científicos.
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Sincrotrón AlbaEl Sincrotrón ALBA es una infraestructura científica de tercera genera-ción y la más importante del Mediterránea. Situado en la población de Cerdanyola del Vallés, este complejo de aceleradores de electrones, per-mite visualizar la estructura atómica y molecular de los materiales así como estudiar sus propiedades.
Actualmente, ALBA tiene ocho líneas de luz operativas que se destinan a la investigación en biociencias, la materia condensada (nanociencias y propiedades magnéticas y electrónicas) y la ciencia de los materiales.
¡Ven a ver la insignia científica!
08:00, 11 de julio, 2018
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Visitas
Asambleas Generales de
FEBiotec
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Asambleas generales de FEBiotec
XI Asamblea General Ordinaria
XVII Asamblea General Extraordinaria
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Se convoca a todos los socios de FEBiotec a la XIX Asamblea General Extraordinaria de la Federación Española de Biotecnólogos, que se celebrará al término del XII Congreso Anual de Biotecnología:
Lugar: Facultad de Ciencias, Girona .
Fecha: sábado, 14 de julio de 2018.
Hora: 15:15 h- Primera convocatoria: 15:15 h.- Segunda convocatoria: 15:45 h.
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Se convoca a todos los socios de FEBiotec a la XI Asamblea General Ordinaria de la Fede-ración Española de Biotecnólogos, que se celebrará al término del XII Congreso Anual de Biotecnología:
Lugar: Facultad de Ciencias, Girona.
Fecha: sábado, 14 de julio de 2018.
Hora: 9:00 h- Primera convocatoria: 9:00 h.- Segunda convocatoria: 9:30 h.
Nuestro agradecimiento a las entidades que han he-cho posible esta edición del Congreso Anual de Bio-
tecnología 2018:
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Colabora:
Apoyan institucionalmente:
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Patrocinadores
Entidades colaboradoras:
Índice de Autores
118
AArocena, I. 61
BBalmaseda, A. 70Barrero, J. 58, 62Bertran, J. 65Borreguero-Figols, M.J. 57Bosch, F. 46
CCalvet, J. 90Caparrós, D. 47Cironi, P. 62
DDe-Vicente-Martínez, B. 102Diego Martin, B. 78
EEscuer, J.M. 64
FFernández, A. 63Fondevila, F. 92
GGarcía-Cebollada, H. 80García, P. 45González-García, P. 94Guadarrama-Flores, B. 84Guerrero, P. 41Gutiérrez-Salazar, M.V. 82
HHughes-Herrera, D. 72
Índice de Autores
119119
JJonkers, H. 43Juste-Lanas, Y. 76
LLaromaine-Sague, A. 42
MMarín, M.C. 49Martínez-Márquez, A. 86Mesa, J.A. 54Moll, L. 104
NNevot, G. 96Newton, A. 59Núñez-González, A. 106
PPío-Beltrán, J. 44
RRamón D. 56Rodriguez-Pastrana, I. 98Ruiz-López E. 74, 88
SSalanueva, P. 60Serra, M. 64
TTorres, B. 100Txopitea-Elorriaga, M. 108
Índice de Autores
120
VVallet-Regí, M. 48
YYonath, A. 39
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