XXXVII Congreso SEBBM

LIBRO DE RESÚMENES

Pósters XXXVII Congreso SEBBM 2

Granada 204 Pósters Primera edición: Septiembre 204 los autores, 204 XXXVII Congreso de la Sociedad Española de Bioquímica y Biología Molecular Publica: Sociedad Española de Bioquímica y Biología Molecular (SEBBM) Producción editorial: Rubes Editorial, S.L. Sicilia, 253 6º 4ª. 08025 Barcelona 3

Pósters XXXVII Congreso SEBBM Índice Agradecimientos....................................................................... 5 Comité organizador..................................................................... 6 Junta Directiva de la SEBBM.............................................................. 7 Socios protectores de la SEBBM............................................................ 7 Conferencias plenarias................................................................... 8 Simposios............................................................................ S Biomedicina molecular............................................................ S2 Biotecnología de plantas y productos de valor añadido...................................... 5 S3 Estructura y función de proteínas..................................................... 9 Pósters............................................................................... 23 4 P00 II Workshop sobre la Innovación Docente en la Enseñanza de la Bioquímica y Biología Molecular...... 24 P0 Apoptosis.................................................................... 27 P02 Bases moleculares de la patología................................................... 33 P03 Biología del desarrollo........................................................... 50 P04 Biología molecular computacional................................................... 53 P05 Biomembranas y bioenergética..................................................... 55 P06 Bioquímica de la nutrición........................................................ 62 P07 Bioquímica perinatal............................................................ 66 P08 Bioquímica y biología molecular de plantas............................................ 68 P09 Biotecnología molecular.......................................................... 76 P0 Estructura y función de proteínas.................................................... 86 P Genómica y proteómica........................................................... 03 P2 Metabolismo del nitrógeno........................................................ 2 P3 Neurobiología molecular.......................................................... 7 P4 Parasitología molecular........................................................... 25 P5 Radicales libres y estrés oxidativo................................................... 33 P6 Regulación de la expresión génica y dinámica del genoma.................................. 4 P7 Regulación metabólica........................................................... 49 P8 Señalización celular............................................................. 59 P9 Transgénesis en mamíferos........................................................ 73 P20 Transportadores de membrana...................................................... 75

Granada 204 Pósters Agradecimientos Nuestro agradecimiento a las entidades públicas y privadas que han colaborado económicamente en la realización del XXXVII Congreso de la SEBBM. Ministerio de Economía y Competitividad Consejo Superior de Investigaciones Científicas (CSIC) Junta de Andalucía Universidad de Granada Parque de las Ciencias Turismo Ciudad de Granada Fundación BBVA Fundación Lilly Fundación Ramón Areces L Oréal For Women in Science FEBS PABMB Bio-Rad Canvax BIOTOOLS Condalab Cultek Ecogen Eppendorf Gilson Izasa-Werfen Neuron Panreac Applichem Sarstedt StabVida Vitro Fisher Scientific Sigma 5

Pósters XXXVII Congreso SEBBM Comité organizador Presidente Juan Luis Ramos (Estación Experimental del Zaidín, CSIC, Granada - Abengoa Research, Sevilla) Comité ejecutivo Federico Mayor Menéndez (presidente de la SEBBM, Centro Biología Molecular «Severo Ochoa», Universidad Autónoma de Madrid) Miguel Alaminos Mingorance (Facultad de Medicina, Universidad de Granada) María Dolores Girón González (tesorera, Facultad de Farmacia, Universidad de Granada) Tino Krell (Estación Experimental del Zaidín, CSIC, Granada) Irene Díaz Moreno (responsable de Congresos y Cursos de la SEBBM, Instituto de Bioquímica Vegetal y Fotosíntesis, ciccartuja, CSIC-Universidad de Sevilla) Miguel Ángel Navarro Carretero (Instituto de Parasitología y Biomedicina «López-Neyra»-CSIC, Granada) Enrique de la Rosa Cano (responsable de Grupos de la SEBBM, Centro de Investigaciones Biológicas, CSIC, Madrid) Joaquín Ros i Salvador (coordinador de la Comisión Asesora de Congresos SEBBM, Facultad de Medicina, Universidad de Lérida) Rafael Salto González (secretario, Facultad de Farmacia, Universidad de Granada) María Dolores Suárez Ortega (vicepresidenta, Facultad de Farmacia, Universidad de Granada) Otros miembros del Comité organizador - Junta Directiva de la SEBBM Alicia Alonso Izquierdo (vicepresidenta y Responsable de Relaciones Internacionales de la SEBBM, Departamento de Bioquímica, Facultad de Ciencias, Universidad del País Vasco) Juan P. Bolaños Hernández (responsable del Portal Electrónico de la SEBBM, Instituto de Biología Funcional y Genómica, IBFG, Universidad de Salamanca) Carme Caelles Franch (responsable de Jóvenes de la SEBBM, IRB-Barcelona, Universidad de Barcelona) Marta Cascante Serratosa (responsable de Cónsules de la SEBBM, Facultad de Biología, Universidad de Barcelona) Crisanto Gutiérrez Armenta (tesorero de la SEBBM, Centro Biología Molecular «Severo Ochoa», CSIC- UAB, Madrid) Almudena Porras Gallo (secretaria Científica Electa de la SEBBM, Facultad Farmacia, Universidad Complutense de Madrid) Isabel Varela Nieto (secretaria Científica de la SEBBM, Instituto de Investigaciones Biomédicas, CSIC-Universidad Autónoma de Madrid) Otros miembros del Comité organizador - Comité local: Mª José Alejandre Pérez (Facultad de Ciencias, Universidad de Granada) Matilde Barón Ayala (Estación Experimental del Zaidín, CSIC, Granada) Andrés Belver Cano (Estación Experimental del Zaidín, CSIC, Granada) Francisco Gamarro Conde (Instituto de Parasitología y Biomedicina «López-Neyra», CSIC, Granada) Juan José Lázaro Paniagua (Estación Experimental del Zaidín, CSIC, Granada) Ana Linares Gil (Facultad de Ciencias, Universidad de Granada) Eduardo López-Huertas León (Estación Experimental del Zaidín, CSIC, Granada) Esperanza Ortega Sánchez (Facultad de Medicina, Universidad de Granada) Mariam Sahrawy Barragán (Estación Experimental del Zaidín, CSIC, Granada) Luisa María Sandalio González (Estación Experimental del Zaidín, CSIC, Granada) Alberto M. Vargas Morales (Facultad de Farmacia, Universidad de Granada) 6

Granada 204 Pósters Junta directiva de la SEBBM Presidente Federico Mayor Menéndez (202-206) Vicepresidenta Alicia Alonso Izquierdo (200-204) [Relaciones exteriores y COSCE] Secretaria Isabel Varela Nieto (200-204) [Divulgación] Tesorero Crisanto Gutiérrez Armenta (202-206) Vocales Marta Cascante Serratosa (200-204) [Cónsules] Enrique de la Rosa Cano (200-204) [Grupos Científicos] Juan Luis Ramos Martín (200-204) [Empresa y Patrocinadores] Juan Pedro Bolaños Hernández (202-206) [Página web] Carmen Caelles Franch (202-206) [Jóvenes Investigadores] Irene Díaz Moreno (202-206) [Congresos y Cursos] Secretaria Electa Almudena Porras Gallo (202-204) Socios protectores de la SEBBM Los Socios protectores de la Sociedad Española de Bioquímica y Biología Molecular (SEBBM) contribuyen al progreso de la ciencia. 7

Pósters XXXVII Congreso SEBBM Conferencias Plenarias 8

Granada 204 Conferencias Plenarias Conferencia inaugural Alberto Sols Fundación BBVA CP0- (R0-) Selfish genes vs selfish metabolism: how environmental bacteria conquer the chemical space Víctor de Lorenzo Centro Nacional de Biotecnología, CSIC, Madrid-Cantoblanco, ES Bacteria that colonize sites polluted by industrial waste are capable of metabolizing synthetic and recalcitrant chemicals that have been in the biosphere for only a few years. This capability is orchestrated by the integration of environmental and physiological signals into regulatory systems that tightly control the expression of genes that are in charge of degrading such molecules. The emergence of these capabilities is due not only to the adaptation of catabolic enzymes acting on new substrates, but also to the emergence of new regulators that firmly control the expression of the genes involved in the production of catabolic enzymes. This scenario provides a good case to examine how transcriptional factors that respond to small molecules can adjust their specificity to novel signals, the significance of the effects of individual changes on overall behaviour of the evolving regulators and the role of other environmental and physiological circumstances in the process. Biological bottlenecks for biodegradation of recalcitrant compounds include [i]unfavourable thermodynamics of (bio) chemical reactions at stake, [ii] lack of specificity of existing pathways and enzymes for novel substrates, and [iii] physicochemical stress encountered in polluted sites. Besides these limitations, bacterial cells also experience increased endogenous oxidative stress during metabolism of aromatic compounds, which is exacerbated when enzymes meet suboptimal substrates. Two experimental systems were employed to examine this issue. First, we studied the regulation of the TOL plasmid-encoded upper and lower operons of the soil bacterium Pseudomonas putida mt-2, a toluene and m-xylene degrader, on the background of endogenous production of reactive oxygen species (ROS) during the process. ROS-responsive dyes and flow cytometry helped to quantify stress associated to each metabolic block and its relationship with redox metabolism. We also examined oxidative stress brought about by the still-evolving 2,4-dinitrotoluene biodegradative pathway in Burkholderia sp. DNT. The dnt pathway of this bacterium apparently evolved from a precursor naphthalene degradation route and the first enzyme (2,4-dinitrotoluene dioxygenase) maintains some activity towards its earlier substrate []. Examination of both in vivo reactions and the associated regulatory system suggests that ROS production is the first bottleneck that evolving pathways have to overcome for dealing with novel compounds [2]. Evolutionary consequences [3] -and some hints for engineering new biocatalysts [4] will be discussed. References [] de las Heras, A., Chavarría, M. and de Lorenzo V. Mol Microbiol 20; [2] Pérez-Pantoja, D., Nikel P.I., Chavarría M. and de Lorenzo, V. [3] de Lorenzo, V. BioEssays 204; 36: 226-35.Phil Trans B Roy Soc 203; 368: 2020377. Conferencia plenaria L Oréal-UNESCO For Women in Science CP02- (R02-) Structures and mechanisms of bacterial transcriptional regulation via oligomeric proteins Xiadong Zhang Centre for Structural Biology, Imperial College London, Londres, UK Bacterial gene transcription depends on the binding of RNA polymerase to a wide range of sigma factors that recognize specific promoter DNA sites to achieve specificity. Two classes of sigma factors exist in bacteria. The σ 70 class includes most sigma factors and the RNAP σ 70 -promoter complex can often spontaneously converts to the open complex, which is competent for transcription. In contrast, the complex between RNAP and its major variant sigma factor σ 54 remains as a closed complex which is incompetent for transcription until ATP hydrolysis-dependent remodelling by activator proteins occurs. The activator proteins, which belong to the AAA+ protein family, bind remotely to the DNA sequences upstream of the transcriptional starting site and contact RNAP-σ 54 through DNA looping. Most AAA+ activators contain three domains: a N-terminal regulatory domain, a central AAA+ domain and a C-terminal DNA binding domain. The regulatory domain senses environmental changes and controls the activities of the AAA+ domain while the AAA+ domain contacts RNAP-σ 54 and uses ATP binding and hydrolysis to remodel the closed complex. In addition, bacteria gene transcription can be inhibited though simple blockage of promoter sites. Over the last few years we have used a combination of X-ray crystallography, cryo-electron microscopy single particle analysis and functional analysis to understand why RNAP-σ 54 remains as a closed complex, how the AAA+ activator interacts with and induces changes in RNAP-σ 54 that ultimately lead to transcriptional activation and how binding and hydrolyzing ATP are coupled to the activation process. I will present our results and explain why RNAP-σ 54 is unable to proceed to transcription, how a hexameric AAA+ protein interacts with and remodels the asymmetric RNAP-σ 54 -DNA using ATP binding and hydrolysis, how these activators are organised at the enhancer-binding site and how their ATPase activity is controlled by both the regulatory and DNA-binding domains. In addition, I will discuss how oligomeric proteins interact with their DNA operators in order to achieve repressive functions. Conferencia plenaria Leloir CP03- (R03-) The brain speaks back to the ear: molecules, physiology and pathology of the efferent olivocochlear-hair cell synapse Ana Belén Elgoyhen Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Dr. Héctor N. Torres, CONICET, Buenos Aires, AR In bringing information about the world to an individual, sensory systems perform a series of common functions. Each system responds with some specificity to a stimulus and each one employs some specialized receptor cells at the periphery to translate specific stimuli into electrical signals that all neurons can use. That initial electrical event begins the process by which the central nervous system constructs an orderly representation of for example, sounds, odors, tastes and objects. Thus, basic sound detection begins when sound waves strike the eardrum, which transmits that physical stimulus to the organ of Corti within the cochlea, the sensory epithelium of the mammalian inner ear. Here the primary receptor cells known as inner hair cells transform the information into electrical signals that are sent to the central nervous system by the auditory nerve. However, unlike vision, touch and the chemical senses, sound processing is modulated by efferent signals that travel in reverse, from the brain back to the inner ear. One fundamental question in auditory neuroscience is what role(s) this feedback plays in our ability to hear. The presentation will overview our work over the years which has contributed to elucidate the molecules which operate at this efferent olivocochlear-hair cell synapse, how the synapse operates to fine tune amplification in the inner ear and the role of the efferent system in protection from acoustic trauma. 9

Conferencias Plenarias XXXVII Congreso SEBBM Conferencia plenaria Niemeyer - PABMB CP04- (R04-) Caveolin-, a pleiotropic molecular switch in cancer development and progression Andrew F.Q. Quest Laboratorio de Comunicaciones Celulares, Centro de Estudios Moleculares de la Célula (CEMC), Centro de Estudios Avanzados en Enfermedades Crónicas (ACCDiS), Programa de Biología Celular y Molecular, ICBM, Facultad de Medicina, Universidad de Chile, Santiago de Chile, CL Cancer is a leading cause of human suffering and death worldwide, whereby most patient deaths are caused by metastatic dissemination rather than primary tumor growth. Understanding the mechanisms that favor such development is currently an area of great interest given the potential it holds for designing successful therapeutic intervention strategies. A central dogma in cancer research over the last decades has been that changes at the molecular level, referred to as gain-of-function in oncogenes or lossof-function in tumor suppressor genes, contribute to the genesis of this disease. Because it is generally thought that any given protein will belong to one or the other category, but not to both, treatment strategies will in general terms seek to enhance tumor suppressor and block oncogene function. Paradoxically, Caveolin- (CAV), a member of the caveolin family of scaffolding proteins, is implicated in cancer development and progression both as a tumor suppressor and promoter of metastasis. In recent years, research from this laboratory has sought to shed light on this enigma. Tumor suppression by CAV was linked to E-cadherin-dependent suppression of genes, including survivin and cyclooxygenase-2, and augmented apoptosis. However, in the absence of E-cadherin, CAV promotes metastasis. More recent studies implicate CAV tyrosine phosphorylation and activation of a novel Rab5-Rac signaling axis in enhanced tumor cell migration, invasion and metastasis. In the presence of E-cadherin, signaling via this pathway and metastasis are suppressed. Thus, CAV switches roles in an E-cadherin-dependent manner. Understanding such context-dependent variations in protein function has important ramifications for our basic understanding of signal transduction processes and cancer, as well as for the development of successful strategies to treat the disease. Acknowledgements: FONDECYT-FONDAP 5300, FONDECYT 30250, ACT (AFGQ). posttranscriptional regulation of gene expression. Examples will be presented that highlight the role of structural changes and conformational dynamics in the recognition of the 3 splice site RNA during eukaryotic pre-mrna splicing, translational regulation and RNA stability. Conferencia plenaria de clausura Fundación Ramón Areces CP06- (R06-) Understanding the role of proteolysis in disease Charles S. Craik University of California San Francisco, San Francisco, US Virtually any biological process can be linked to a proteolytic event. With approximately 2% of the human genome encoding a protease a plethora of these enzymes exist, several of which have already been shown to play roles in diverse physiological processes including development, innate and adaptive immunity, cell cycle regulation and apoptosis. In situations where a unidirectional signal is required, the hydrolysis of a peptide bond can provide an irreversible, one-way event in a complex signaling pathway. Similarly, the genomes of most other organisms ranging from viruses and microorganisms to metazoans have 2 to 4% of their genomes dedicated to proteases. In cases where there is a direct link between the proteolytic event and disease, significant opportunities exist for therapeutic intervention. For these reasons, there has been a great deal of interest in protease biology and in dissecting the complex regulation, localization and activation of protease function. Identifying the actual proteases involved in physiological events, locating the natural substrates of the enzymes and selectively regulating their activity is of prime importance to the field. This talk will focus on a highly important subset of the large area of proteolysis to provide a window into this rich area of research. Methodologies will be presented that allow the global activity of proteolysis to be determined in complex biological systems and permit the non invasive imaging of protease activity in various disease states. These efforts to understand the mechanism of proteolysis in a biological context and in several cases, the relationship between proteolysis and disease are providing insights regarding how best to regulate proteolysis in infectious diseease and cancer. Conferencia plenaria FEBS National Lecture CP05- (R05-) Dynamics of protein-rna interactions in posttranscriptional regulation of gene expression Michael Sattler Institute of Structural Biology, Helmholtz Zentrum München, Neuherberg, and Center for Integrated Protein Science Munich and Biomolecular NMR, Technische Universität München, Garching, München, DE Eukaryotic multi-domain proteins play crucial roles in the regulation of gene expression and cellular signaling. The structure of these proteins often depends on dynamic domain arrangements that are modulated by binding to RNA and/or other proteins. We employ integrated structural biology combining solution techniques such as NMR-spectroscopy and small angle scattering experiments with crystallography to study the structure and dynamics of multi-domain proteins involved in various aspects of 0

Granada 204 Pósters Simposio : Biomedicina molecular

Simposios XXXVII Congreso SEBBM S. Enfermedades moleculares S.- (R.-) Pancreatic cancer: From molecular understanding to personalized treatment Manuel Hidalgo Centro Nacional de Investigaciones Oncológicas, Madrid, ES Pancreatic cancer remains one of the most deadly cancers. Over the last few years, the genomic landscape of pancreatic cancer as well as precursor pancreatic cancer lesions have been deciphered in great depth. These studies show that PDA develops as the consequence of accumulation of mutations in key oncogenes and tumour suppressor genes. The disease, once established, is characterized by high complexity, heterogeneity and genomic instability. Despite this facts, some patients harbour actionable mutations which targeting has resulted in significant clinical benefit. Indeed, one of the most active areas of research in PDA is the development of strategies and approaches to personalize the treatment of patients. This is a complex field that can be tackle from many complementary angles. Our group has been interested in using patient derive xenogaft (PDX) models, aka Avatar mouse models, to guide cancer treatment. A piece of freshly collected tumour is implanted in immunodeficient mouse models, expanded, treated with different anticancer agents alone and in combination to select the most effective drug/regimen to treat the patient cancer. Our data show that the approach is highly predicted but, because of complexity and cost issues, not widely applicable to clinical practice at the present stage. To solve some of these limitations we are working on different aspects. One area is technological development to increase the take rate of tumours and to speed time to engraftment and expansion time. Currently, these figures are approximately 60-80 % and 5-7 months. Studies are in progress to optimize this aspect. Another key question is the selection of agents, both alone and in combination, to be tested in the model. In this regard, it is important to integrate biomarker assessment in the tumour to pre-select a series of treatment candidates that can then be tested in the PDX models. To this end, we have now integrated next generation sequencing and assessment of copy number variation in patient s tumour. These studies provide us with an unbiased overview of the tumour genomic landscape. From this data, using different bioinformatics and biological methods we extract the most relevant drug targets that are then bench tested against the patient Avatar mouse model to select the most effective treatment. Another area of great interest in PDA therapeutics is the cancer microenvironment. PDA is known for a flourish cancer stroma composed of extracellular matrix and cells including inflammatory, immune and cancer associate fibroblast. Strategies aiming to eliminate the cancer stroma with agents such as hyaluronidase and Hh inhibitors among others have received substantial attention. nabptx, an agent proposed to target SPARC, one of the key elements in the PDA stroma, has shown improvement in overall survival and has received regulatory approval for this disease. Agents in this category will also be reviewed. Finally, strategies to target the cancer stem cell will be presented. Laboratory studies have shown the presence of a small percentage of cells in PDA tumours with stem properties. These cells can be identified by membrane markers and are considered to be resistant to chemotherapy and radiotherapy. It is possible, that CSC is responsible for cancer failure after definitive chemotherapy and radiotherapy and there is significant interest in developing agents to selectively eliminate these cells. S.-2 (R.-2) Assessing the therapeutic role of Vav oncoproteins in high-incidence diseases Xosé R. Bustelo, Salvatore Fabbiano, Javier Robles, Luis Francisco Lorenzo, María Barreira, Mauricio Menacho-Márquez Centro de Investigación del Cáncer, Salamanca, ES Although there is a wide consensus regarding the potential therapeutic role of Rho/Rac GDP/GTP exchange factors (GEFs), we have no formal demonstration that such idea is true for most high-incidence diseases. Tackling this issue has been in fact rather difficult so far, since the human genome contains more than 70 GEFs that, in many cases, are coexpressed in the same cell types and tissues. Due to this, it is of paramount importance to utilize disease-mimetic animal models to characterize unequivocally the spectrum of GEF-dependent diseases, identify the best therapeutic targets of the GEF family for specific high-incidence diseases or disease subtypes and, in addition, unveil the GEF-dependent Achilles heels present in those diseases that can be used to devise new ways to attack them pharmacologically. In our lab, we are addressing the above issues using as working model the Vav GEF subfamily. The three members of this subfamily present in mammalian species (Vav, Vav2, Vav3) are characterized by being directly regulated by phosphorylation on specific tyrosine residues. Due to this, these GEFs are specialized in connecting stimulated upstream protein tyrosine kinases with the activation of downstream Rho/Rac GTPases during both normal and pathophysiological signaling responses. To this end, we are using both standard and secondgeneration genetically modified mice to assess the pros and cons of the inactivation of these proteins in a number of high-incidence diseases. Using this approach, we have discovered that two Vav subfamily members (Vav2 and Vav3) play critical roles in breast and skin primary tumorigenesis, the metastasis of cancer cells to the lung, obesity, and obesity-linked comorbodities (i.e., metabolic syndrome, liver esteatosis, type II diabetes). We have also discovered that the inactivation of any of those two proteins also leads to negative effects in the cardiovascular system. However, such collateral defects can be easily bypassed by treatments with currently available anti-hypertension therapies. Finally, the dissection of the role of Vav proteins in these diseases has allowed us to discover biological programs and gene signatures that have favored the molecular understanding of those diseases, the identification of new targets, and the diagnosis of some of those diseases. In this talk, we will provide an overall view of the progress made in these areas. S.-3 (R.-3) Muerte celular, senescencia y autofagia en la pérdida de audición relacionada con la edad: regulación por IGF- Isabel Varela-Nieto, Adelaida Celaya 2, Alejandro Gibaja 2, Sara Pulido 2, Rocio de Iriarte 2, Marta Magariños 3 Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), IdiPAZ y CIBERER, Madrid, ES, 2 Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM) y CIBERER, Madrid, ES, 3 Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Facultad de Ciencias (UAM) y CIBERER, Madrid, ES La deficiencia congénita en el factor de crecimiento similar a la insulina tipo (IGF-) es una enfermedad rara humana que produce alteraciones severas del crecimiento y sordera neurosensorial. Este factor neurotrófico es fundamental en la diferenciación postnatal tardía de la cóclea, su ausencia causa muerte por apoptosis de las neuronas auditivas tipo I, y otras alteraciones celulares en el receptor periférico y en las vías auditivas centrales. Entre los mecanismos implicados se ha descrito la activación de quinasas de estrés (MAPK8/9 y 4-FoxP3) y la inhibición de rutas de supervivencia (AKT), de proliferación (MAPK/3-FoxM/p27Kip) y de diferenciación celular (MEF2). El IGF- en la edad adulta es un protector ótico, mantiene la fisiología coclear y promueve la supervivencia de las neuronas auditivas. Durante el envejecimiento, se produce senescencia neuronal, un aumento en la expresión de genes de la maquinaria autofágica (Becn, Atg4b yatg5) y en los niveles de marcadores proteicos de autofagosomas (LC3-II y p62), neuroinflamación y una disminución en los niveles de IGF- que progresa pari pasu con la pérdida auditiva relacionada con la edad (ARHL). El componente neurodegenerativo de la ARHL empeora en situaciones patológicas de déficit de IGF-, agudizándose el fenotipo molecular, celular y funcional, e incluso predispone al receptor auditivo a sufrir un mayor daño cuando se somete a estrés. 2

Granada 204 Simposios En conclusión, el IGF- es un neuroprotector ótico que favorece la supervivencia celular, mientras que su déficit promueve procesos de inflamación que producen un aumento del daño en la cóclea. Este trabajo ha sido fi nanciado por los proyectos FP7-innova2 AFHELO y la MCA TARGEAR. S.2 Señalización celular «cascadas y dianas» S.2- (R.2-) The loss of memory in Alzheimer disease Jesús Ávila de Grado Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, ES Memory impairment in Alzheimer disease (AD) could be related to a defect in the function of hippocampal region of an AD patient. In this region, dentate gyrus plays an important role in the formation of new memories. The study of neurogenesis in dentate gyrus, in mouse models for AD, has indicated some important features that could also take place in Alzheimer disease patients. S.2-2 (R.2-2) The role of the JNK pathway in insulin resistance Carme Caelles Universidad de Barcelona, Barcelona, ES During the last decade, the c-jun N-terminal kinase (JNK) has emerged as a major regulator of the insulin signalling and, hence, glucose homeostasis. By directly targeting the insulin receptor substrate (IRS)- and -2 for serine phosphorylation, JNK inhibits insulin signalling at very early steps. Actually, JNK is activated by insulin and acts as a negative feedback mechanism to turn off insulin signal under physiological conditions. However, abnormal JNK activation due to stress, such as oxidative or endoplasmic reticulum stress, or pro-inflammatory signals induces, by this IRS-phosphorylation dependent mechanism, insulin resistance. In fact, the insulin-sensitizing drugs and peroxisome-proliferator activated receptor (PPAR) γ ligands thiazolidinediones (TZDs) restore glucose homeostasis through inhibition of JNK, further supporting the role of this kinase as a major mediator of obesity-induced insulin resistance. In addition to the role of JNK in peripheral insulin-target tissues, JNK activity also regulates insulin action in pancreatic β-cells. In this regard, in vivo ectopic activation of JNK this cell type renders a glucose-intolerance phenotype in mice due to the impairment of glucose- and insulin-induced insulin secretion and gene transcription. Moreover, results form these mice demonstrate a direct action of TZDs on pancreatic β-cells as TZD treatment inhibits this ectopic JNK activation and, thereby, restores insulin signalling and glucose- and insulin-induced secretion in pancreatic islets, and glucose tolerance in the mice. S.2r-3 (R.2-3) Deciphering the insights of poly(adp-ribosylation) in metastasis Francisco Javier Oliver Pozo Instituto de Parasitología y Biomedicina López - Neyra, CSIC, Granada, ES Poly(ADP-ribose) polymerases (PARPs) are a group of DNA-dependent nuclear enzymes (also named ARTD) which catalyze the synthesis and transfer of negatively charged ADP-ribose moieties from nicotinamideadenine-dinucleotide (NAD + ) to a number of target protein substrates, leading to the alteration of chromatin associated proteins. PARP-, the founder member, is an active player in tumor adaptation to metastasis and PARP inhibitors, recognized as promising therapeutic agents against homologous recombination deficient tumors, have novel properties responsible for the anti-metastatic actions in different tumor settings. Poly(ADP-ribosyl)ation modulates pro-metastasic activities such as hypoxic response, angiogenesis and epythelial to mesenchymal transition (EMT). Furthermore, key transcription factors are fine-tuned through this action, helping to the adaptation of tumor to a hostile microenvironment, the recruitment of new vessels, and stimulate the cellular changes promoting EMT. In this presentation we summarized some of the findings that focalize on PARP- s action on tumor aggressiveness, suggesting new therapeutic opportunities against an assembly of tumors not necessarily bearing DNA repair defects. S.3 Ingeniería tisular y medicina regenerativa S.3- (R.3-4) BIOLAMINATION for customised, rapid tissue fabrication: printer optional Robert Brown University College London. Institute of Orthopaedics & Musculoskeletal Sciences, RNOH, Stanmore Campus, Londres, UK A quiet revolution is happening under the umbrella of tissue engineering as we begin to understand that there are two distinct approaches available for producing tissues. Not surprisingly, the approach we select has a profound effect on the technology we use. Firstly, and most familiar, is the idea of growing tissues by cultivation of cells in/on a substrate (often in bioreactors). Secondly we can directly fabricate simple living tissues, in the same way we make cell-phones. In this case there is little or no contribution from the cells, though they are incorporated as one of the basic building blocks. Fabricating tissues directly is a concept which has entered largely from public excitement around the extension of ideas in 3D bio-printing to incorporate living cells and proteins into the system. In fact 3D cell-printing is only one of a family of approaches which is better termed BIO-LAMINATION, in which thin layers (micron scale) of proto-tissue are laid down in series to build up a stack and produce the gross-scale tissue. In fact although bio-printing provides the popular image, it is presently far from the most effective example of fabrication by bio-lamination, as technical problems of cell survival and natural matrix polymerisation are complex. Other bio-lamination approaches include electro-spinning and cell and matrix layering. Although attractive, the need for bio-printing and spinning approaches to assemble the X-, Y-, AND Z-planes simultaneously creates a technical hurdle. Matrix and cell layering techniques avoid this by firstly mass-fabricating the X-Y plane layers, then stacking them to give the Z-plane in a separate stage. Cell-rich constructs are fabricated by expansion of cell sheets on specialised surfaces, matrix-rich X-Y layers by rapid cocompression of cells and matrix proteins (eg collagen). Bio-lamination fabrication has the capacity to mass produce real tissues (cells embedded in a native extracellular matrix) in minutes. They can be mass- produced reproducibly, economically, with simple or complex stacks of tissue layers. They are already available for 3D tissue drug or disease screening, customised grafts and advanced drug delivery. But however we produce the component laminae, they require a number of special processing features. These include the need (i) to incorporate living cells INTO the fabric of the matrix at time zero (so no cell-seeding stage but conditions must be 3