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Unveiling Novel Functions of the Trascriptional Repressor HDAC7 in B Lymphocyte Development

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Unveiling Novel Functions of the Trascriptional Repressor HDAC7 in B Lymphocyte Development Unveiling novel functions of the trascriptional repressor HDAC7 in B lymphocyte development Alba Azagra Rodríguez Aquesta tesi doctoral està subjecta a la llicència Reconeixement- NoComercial – SenseObraDerivada 4.0. Espanya de Creative Commons. Esta tesis doctoral está sujeta a la licencia Reconocimiento - NoComercial – SinObraDerivada 4.0. España de Creative Commons. This doctoral thesis is licensed under the Creative Commons Attribution-NonCommercial- NoDerivs 4.0. Spain License. FACULTAT DE BIOLOGIA PROGRAMA DE BIOMEDICINA UNVEILING NOVEL FUNCTIONS OF THE TRANSCRIPTIONAL REPRESSOR HDAC7 IN B LYMPHOCYTE DEVELOPMENT Memòria presentada per Alba Azagra Rodríguez per optar al grau de Doctor en Biomedicina per la Universitat de Barcelona Aquesta tesi s’ha realitzat al Grup de Diferenciació cel·lular a les instal·lacions del Programa d’Epigenètica i Biologia del Càncer (PEBC) de l’Institut d’Investigació Biomèdica de Bellvitge (IDIBELL, sota la direcció de la Dra Maribel Parra. Directora de tesi: Doctorand: Tutor de tesi: Dr Maribel Parra Bola Alba Azagra Rodríguez Dr Albert Tauler Girona Juliol 2019 AGRAÏMENTS 3 4 Agraïments “I will discover the cure of cancer”. Aquesta frase era el meu recurs més usat a la ESO per exemplificar el futur simple a anglès, una frase que amb el pas dels anys s’ha tornat massa simple i innocentment ambiciosa. De vegades va bé recordar per què ens vam ficar en aquest món i quins eren els nostres primers pensaments, desitjos i objectius, fossin més o menys realistes, perquè segurament eren els més entregats, purs i desinteressats. El meu primer desig de curar el càncer contenia una visió utòpica del món de la ciència, essent els pacients la principal prioritat, i involucrava la col·laboració de tots els membres del camp per poder arribar abans al coneixement i la cerca de teràpies. Per sort, més d’una persona durant aquests anys de tesi m’ha portat a recordar les bases d’aquest primer desig. M’agradaria començar amb el Víctor Deroncelé, tutor del treball de recerca que ens va transmetre la seva passió per la ciència de la manera més amena i amb gran paciència. Va ser un privilegi poder viure i experimentar què era treballar en un laboratori i poder començar a valorar amb una lleugera idea si aquesta vessant de la ciència et podia agradar o no pel teu futur. A l’Antonio García de Herreros, l’únic professor del grau al que vaig suspendre una assignatura. Tot i així, em va agafar per fer les pràctiques del TFG I em va donar la oportunitat de treballar en un grup de recerca i d’espavilar-me dins d’un laboratori (no m’ho va deixar de recordar fins l’últim dia que vaig estar allà). Aquí aprofito per agrair també a Josep Baulida, el que va ser el meu tutor del treball i que em va supervisar sempre de bon grat i amb predisposició a qualsevol cosa que em faltés, i a Josué Curto que m’ensenyés de la manera més poc convencional, sempre amb un somriure i un moment divertit. Ja anant al doctorat, m’agradaria agrair a la Maribel, la meva directora de tesi. Gràcies per confiar en mi i donar-me la oportunitat de realitzar la tesi al teu grup, sense mirar ni jutjar notes. Gràcies per tot l’ensenyament rebut durant la tesi. Gràcies per la paciència infinita als meus oblits i despistes. Gràcies per la comprensió en els moments difícils. Encara que pugui semblar absurd pels que no són del camp, crec que els que hi estan ficats em podran entendre millor, i és que em sento afortunada de tenir una cap de grup que sigui humana a més de gran investigadora. Malauradament, és una qualitat molt menys freqüent del que tocaria. Seguint amb els membres del nostre petit grup, amb el quals es respira amb tots ells molt bona sintonia, continuem amb el nostre post-doc, l’Oriol. Un gran potencial que es va haver d’adaptar ràpidament a un camp completament diferent al que feia. Disposat sempre a ajudar…i a assabentar-se de tot! Gràcies per tots els consells i recomanacions de la tesi, gràcies per les aportacions de la teva experiència al laboratori, pels moments de poyata compartits, i pels que queden. A l’Ainara, la nostra minion, la joveneta del grup. Tens grans facultats en múltiples sentits, eres buena y lo sabes ;) Gràcies per tota l’ajuda amb els experiments, amb els escrits, aquesta última etapa d’escriure ha estat una mica més fàcil gràcies a tu...i gràcies pels entranaments de gym! Un gran plaer haver-te pogut ensenyar en els teus inicis, veure que aviat sabràs molt més que jo i haver pogut compartir poyata, molts riures i ficades de pota amb tu, jefa. Espero que encara ens quedin uns quants més. 5 Y a mi querida Olguiña…hemos estado mucho tiempo las dos solas, así que me tomo la libertad de explayarme un poco más. Desde el primer día que llegué me enseñaste, me aconsejaste, me cuidaste y me ayudaste en todo lo que pudiste, con la mejor voluntad y un gran humor. Gran compañera…y amiga. En el laboratorio se pasan muchas horas cada día, y cuán largas se harían sin momentos como los que hemos pasado, tanto en la poyata como en cultivos. Aunque por un lado me hubiera gustado conocerte en otra época de tu vida para poder compartir esos momentos post-lab en los que te apetece una cerveza (o unas cuantas) y olvidar el día hablando de cualquier cosa o salir a descubrir sitios algún fin de semana entre risas, me alegro de haber tenido la oportunidad de conocerte en una época de tu vida tan especial. Una época en que la vida te ha dado muchas experiencias, pero no dejas de querer aprender cada día gracias (en gran parte) a dos maravillosos pequeñines muy moviditos con una curiosidad y una avidez alucinante. Y con lo que aprendes de ellos tomo nota para otro momento que siempre viene bien saber de estas cosas! Tienen mucha suerte de tenerte como madre…en serio, y te deben una muy grande por la falta de sueño, aunque ni el estar sin dormir hace que pierdas esa risa tan viva y tan única que te hace tan especial. Te voy a echar mucho de menos el día que me vaya….mucho. Querría también agradecer a otros miembros del PEBC. Dentro del mismo laboratorio, agradezco a los miembros del grupo de Esteban Ballestar la ayuda prestada en ocasiones cuando fue necesaria, pero especialmente quería agradecer a Natalia, former member del grupo vecino y compañera de unas cuantas aventuras en la ciudad y la provincia, de las cuales me guardo un entrañable recuerdo, a Clara, dulce y alegre con la que era un gusto compartir laboratorio, i al Xec, un company al que li acabes agafant gran carinyo, a més de ser un crack en bioinformàtica és un sol, disposat sempre a ajudar-te i explicar-te quan ho necessites. Saliendo del laboratorio sin avanzar mucho, a las chicas del PEBC6, Sandra, Marta, Laura, Clara y Marina. Con las que es un placer coincidir dentro y fuera del laboratorio, sea en la montaña o en una fiesta de Zumba. Sandra y Jordi, tenéis un corazón que no os cabe en el pecho, sois unos soles…el uno para el otro. Marta, no te lo digo mucho para que no te lo creas, pero… te voy a echar de menos, a tus lametones no por eso! Chicas, se os echará de menos por los pasillos...incluyendo la risa de Sandra, las salidas de Laura, las imitaciones de Clara y las palabras dulces de Marina. A l’Adrià, un tros pa i campió imbatible d’hores treballades en aquell departament, una màquina que t’ajudava encara que no tingués temps ni de respirar. A Pedro, mestre de cerimònies i temps lliure del departament, un gran personatge en el millor dels sentits, un plaer i una alegria tenir-te pels passadissos. A Fer, el pilar del departamento, una fuente de sabiduría de cualquier tema que se te pueda pasar por la cabeza, dispuesto a ayudarte, aconsejarte y enseñarte con calma e infinita paciencia. Agrair també a tota aquella gent maca que et creues cada dia i que et fan el dia més amè i fàcil amb un simple somriure, com la Marta, Eva, Ana, Nico, Maria, Jèssica, Paula, Olga de la Caridad, Alberto i, tanmateix, al Carles i la Patri per tots els dinars de tupper i les rialles compartides. Gracias a las chicas de cocina por facilitar el trabajo y su buen humor, sobretodo a Sonia del Oro. Gràcies també al Jaume, la Sònia i l’Ester per totes les hores d’ajuda al sorter, pels consells sobre les millors combinacions de separació i pel temps dedicat a intentar solucionar els problemes que he pogut tenir, sigui en una facultat o altra. 6 Sortint de l’Hospital, hi ha persones molt importants a la meva vida a les quals vull agrair la companyia i suport durant els anys de tesi… i anys enrere. Empezando por ti Alba, un ejemplo de constancia y de esfuerzo. Una persona que será una gran enfermera y un pilar clave para todo paciente, ya que aparte de poseer el conocimiento necesario para atender a todo enfermo en el aspecto más estrictamente médico, tiene esa gracia natural (esa salsa interna que llevas en la sangre), ese gran corazón lleno de humanidad y empatía y esa vitalidad envidiable que hacen que todo se lleve un poco mejor. Gracias por regalarme tu risa tan viva y esos momentos de charla tan buenos querida amiga.
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