Estudio De Los Cofactores De La Tubulina En Gametos Humanos Victoria Jiménez Moreno

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Estudio De Los Cofactores De La Tubulina En Gametos Humanos Victoria Jiménez Moreno UNIVERSIDAD DE CANTABRIA FACULTAD DE MEDICINA DEPARTAMENTO DE BIOLOGÍA MOLECULAR ESTUDIO DE LOS COFACTORES DE LA TUBULINA EN GAMETOS HUMANOS Mª Victoria Jiménez Moreno Santander, Febrero 2015 Estudio de los Cofactores de la tubulina en gametos humanos Departamento de Biología Molecular Facultad de Medicina Universidad de Cantabria ESTUDIO DE LOS COFACTORES DE LA TUBULINA EN GAMETOS HUMANOS Memoria presentada por la Lda. Mª Victoria Jiménez Moreno para aspirar al título de Doctor por la Universidad de Cantabria Directora de Tesis Dra. Mónica López Fanarraga Profesora Titular de Bioquímica y Biología Facultad de Medicina, Universidad de Cantabria Santander, Febrero 2015 1 Estudio de los Cofactores de la tubulina en gametos humanos Dña Mónica López Fanarraga, Profesora Titular de Bioquímica y Biología Molecular de la Facultad de Medicina de la Universidad de Cantabria CERTIFICA: que Dña. Mª Victoria Jiménez Moreno ha realizado bajo mi dirección el trabajo que lleva por título “Estudio de los cofactores de la tubulina en gametos humanos” Considero que dicho trabajo se encuentra terminado y reúne los requisitos necesarios para su presentación como memoria de doctorado por el interesado, al objeto de poder optar al título de Doctor por la Universidad de Cantabria. Santander, Febrero de 2015 2 Estudio de los Cofactores de la tubulina en gametos humanos Dedicada a mis padres por enseñarme a tener ilusiones y a perseguir mis sueños 3 Estudio de los Cofactores de la tubulina en gametos humanos Agradecimientos Agradecimientos La realización de esta Tesis Doctoral no habría sido posible sin todas aquellas personas que se han cruzado en mi camino tanto a nivel profesional como personal y que han contribuido a ella con su granito de arena, incluidos todos los pacientes que de forma altruista y voluntaria me han donado su material biológico sin el cual no podría haber realizado este estudio. En primer lugar quiero dar las gracias a mi directora de tesis, Mónica López Fanarraga, por toda la paciencia, dedicación y conocimientos científicos que has compartido conmigo. Por enseñarme a pensar de forma científica y hacerme razonar cada una de las dudas, preguntas o respuestas que te he realizado durante estos años. Pero sobre todo me gustaría agradecerte que nunca hayas perdido la esperanza en mí y por enseñarme a entender el mundo de la investigación con esa “ilusión” que tú “nunca pierdes” aunque las cosas no vayan bien y que también aplicas en tu vida personal. Agradecer a Juan Carlos Zabala el hecho de abrirme las puertas al mundo de los cofactores de la tubulina y permitirme trabajar en sus laboratorios. También quiero dar las gracias a Juan Carlos Villegas y a Ekaitz Agirregoitia por su inestimada ayuda y generosidad en su trabajo de microscopia electrónica y PCR respectivamente. A Luis Buelta por ayudarme a perseguir mi sueño de realizar la tesis y por su dedicación y paciencia conmigo en mis primeros años de cursos de Doctorado y Suficiencia investigadora. Gracias por esos cafés anuales recordándome que tenía que acabar la tesis, al final surtieron su efecto. También me gustaría dar las gracias a Lorena porque sin todas las horas que has dedicado a enseñarme las técnicas bioquímicas e informáticas, hoy no estaría escribiendo estos agradecimientos. Gracias por tu generosidad, tus consejos, tu sinceridad en nuestras largas conversaciones, por los buenos momentos, y las comidas de los sábados entre gel y gel. Espero que no perdamos nunca estas buenas costumbres. A Laura y a Gerardo por la acogida cariñosa y toda la ayuda que me habéis prestado y todo lo que me habéis enseñado desde el primer momento que llegue al laboratorio. Gracias a los tres por devolverme parte de la ilusión en el trabajo que había perdido por el camino. 0 Estudio de los Cofactores de la tubulina en gametos humanos Agradecimientos Gracias a mis compañeros de la Unidad de Reproducción Asistida y del hospital, por compartir conmigo tantos años de duro trabajo, darme vuestra ayuda para poder realizar mi tesis incluso cuando ha supuesto aumentar vuestra carga laboral y por no perder nunca la ilusión aunque a veces nos hayamos visto en situaciones difíciles. En especial a Cristina y a Elena por recordarme en los momentos bajos que todo esfuerzo lleva su recompensa. A Lourdes y Abel, gracias por revisar mi tesis y corregir mis errores en el campo de la reproducción y porque junto con Josu y Marina lo que empezó como una relación profesional se ha convertido en una relación de amistad. A todos mis amigos, por la paciencia que habéis tenido conmigo siempre y en especial estos últimos años que os he tenido un poco desatendidos. Gracias por escucharme, ayudarme a ser mejor persona, darme buenos consejos y sobre todo por hacerme reír siempre que lo necesito. A Tere, Begoña y vuestras familias, por ser mi hogar en Cantabria. Desde el primer momento que llegue a Santander, habéis cuidado de mí, habéis sido mi refugio donde llorar, reír, desahogarme y siempre me habéis apoyado en todo. Así que solo puedo deciros “GRACIAS” por formar parte de mi vida. A mis hermanos por ser lo mejor que tengo junto con sus familias y mis padres. Quiero daros las gracias por compartir conmigo vuestras vidas y a mis cuñados por tratarme como a una hermana. A todos vosotros por trasmitir el cariño que me tenéis a vuestros hijos a los que adoro y a pesar de la distancia hablan de mí como si me vieran todos los días. A mis 11 sobrinos porque ser los responsables de la sonrisa con la que me levanto cada mañana y a mi sobrina Ana por ayudarme con el índice de la Tesis. Al resto de mi familia, porque es muy fácil vivir sabiendo que tengo tanta gente que me quiere y me apoya. Me gustaría dedicar mis últimas palabras a mis padres, por darme y enseñarme a vivir la vida con ilusión, por mostrarme con vuestro ejemplo lo que significa ser buenas personas y a intentar hacer las cosas lo mejor posible respetando a los demás. Gracias por todas las cosas que os habéis dejado en el camino por ayudarme a cumplir mis sueños. Y no sé cómo serán el resto de los padres, pero lo que sí que se dé fijo es que los míos son los “mejores” padres que me podían haber tocado. 1 Estudio de los Cofactores de la tubulina en gametos humanos Indice INDICE I ABREVIATURAS ................................................................................................................................. 2 II INDICE FIGURAS Y TABLAS ............................................................................................................ 7 II.1 Introducción: ...............................................................................................................................................8 II.2 Materiales y métodos: .................................................................................................................................9 II.3 Resultados: ................................................................................................................................................ 10 II.4 Discusión: ................................................................................................................................................. 12 III INTRODUCCIÓN ............................................................................................................................. 13 III.1 El citoesqueleto: ........................................................................................................................................ 14 III.2 Los microtúbulos: ...................................................................................................................................... 15 III.2.1 Estructura .......................................................................................................................................................... 15 III.2.2 Nucleación de los MT ........................................................................................................................................ 17 III.2.3 Dinámica de los MTs ......................................................................................................................................... 17 III.2.4 Estructuras celulares compuestas por MTs ....................................................................................................... 19 III.3 Tubulinas: ................................................................................................................................................. 20 III.3.1 Estructura de la tubulina ................................................................................................................................... 21 III.3.2 Diversidad en tubulina y .......................................................................................................................... 21 III.3.3 Síntesis de tubulina ............................................................................................................................................ 22 III.3.4 Plegamiento de tubulina y formación del heterodímero .................................................................................... 22 III.4 Los Cofactores del plegamiento de la tubulina: ........................................................................................ 26 III.4.1 Cofactor A ......................................................................................................................................................... 26 III.4.2 Cofactor B ........................................................................................................................................................
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