MECHANISMS REGULATING THE GERMINAL CENTRE REACTION: FUNCTIONAL RELATIONSHIP WITH LINFOMAGENESIS OF ORIGIN B (Q3208604): Difference between revisions
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(Created claim: summary (P836): MOST LYMPHOMAS THAT ARE DIAGNOSED IN THE WESTERN WORLD ORIGINATE FROM MATURE B-LYMPHOCYTES THAT HAVE GONE THROUGH GERM CENTER REACTION (GC). CGS ARE STRUCTURES IN WHICH A SOMATIC REMODELING OF IMMUNOGLOBULIN (IG) GENES TAKES PLACE, WHICH ALLOWS THE GENERATION OF HIGH AFFINITY ANTIBODIES AND CONSEQUENTLY IMPROVES THE QUALITY OF THE IMMUNE RESPONSE. ACTIVATION-INDUCED DEAMINASE (AID) INITIATES THESE REMODELING EVENTS DESAMINING CYTOSINS IN THE DNA...) |
(Changed label, description and/or aliases in en: translated_label) |
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MECHANISMS REGULATING THE GERMINAL CENTRE REACTION: FUNCTIONAL RELATIONSHIP WITH LINFOMAGENESIS OF ORIGIN B | |||
Revision as of 08:42, 14 October 2021
Project Q3208604 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | MECHANISMS REGULATING THE GERMINAL CENTRE REACTION: FUNCTIONAL RELATIONSHIP WITH LINFOMAGENESIS OF ORIGIN B |
Project Q3208604 in Spain |
Statements
205,700.0 Euro
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411,400.0 Euro
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50.0 percent
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1 January 2014
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31 December 2016
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FUNDACION CENTRO NAL DE INV. CARDIOVASCULARES CARLOS III
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40°25'0.12"N, 3°42'12.89"W
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28079
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LA MAYORIA DE LOS LINFOMAS QUE SE DIAGNOSTICAN EN EL MUNDO OCCIDENTAL SE ORIGINAN A PARTIR DE LINFOCITOS B MADUROS QUE HAN PASADO POR LA REACCION DE CENTRO GERMINAL (CG). LOS CGS SON ESTRUCTURAS EN LAS QUE TIENE LUGAR UNA REMODELACION SOMATICA DE LOS GENES DE INMUNOGLOBULINAS (IG), LO QUE PERMITE LA GENERACION DE ANTICUERPOS DE ALTA AFINIDAD Y EN CONSECUENCIA MEJORA LA CALIDAD DE LA RESPUESTA IMMUNE. LA DEAMINASA INDUCIDA POR ACTIVACION (AID) INICIA ESTOS EVENTOS DE REMODELACION DESAMINANDO CITOSINAS EN EL DNA DE LOS GENES DE IG. SIN EMBARGO, LA ESPECIFICIDAD DE AID POR LOS GENES DE IG NO ES PERFECTA Y PUEDE GENERAR MUTACIONES Y TRANSLOCACIONES CROMOSOMICAS EN OTROS SITIOS DEL GENOMA, LO QUE ESTABLECE UNA CONEXION DIRECTA ENTRE LOS CGS Y LA LINFOMAGENESIS. ADEMAS, OTROS MECANISMOS REGULADORES DE LOS CGS, TANTO TRANSCRIPCIONALES COMO POST-TRANSCRIPCIONALES TAMBIEN CONTRIBUYEN A LA PREDISPOSICION DE LOS LINFOCITOS B A LA TRANSFORMACION ONCOGENICA._x000D_ _x000D_ AQUI PROPONEMOS ABORDAR LOS MECANISMOS MOLECULARES QUE REGULAN LA REACCION DE CG CON TRES OBJETIVOS ESPECIFICOS: 1) ENTENDER LA ESPECIFICIDAD DE AID A TRAVES DE UNA APROXIMACION DE SECUENCIACION MASIVA; 2) EXPLORAR EL PAPEL DEL REMODELADOR DE CROMATINA CTCF EN LA REGULACION DE LAS REACCIONES DEPENDIENTES DE AID Y 3) ANALIZAR LA CONTRIBUCION DE MIR-28 A LA FUNCION DEL CG Y SU POTENCIAL COMO AGENTE TERAPEUTICO PARA EL TRATAMIENTO DE LINFOMAS._x000D_ _x000D_ EL LABORATORIO RECEPTOR TIENE AMPLIA EXPERIENCIA EN EL CAMPO DE LA BIOLOGIA DE LINFOCITOS B Y MAS ESPECIFICAMENTE EN LA REGULACION DE LA FUNCION DE AID (RAMIRO ET AL, 2003, 2004, 2005, 2006; SERNANDEZ ET AL, 2008, DE YEBENES ET AL., 2008), Y RECIENTEMENTE HA MOSTRADO POR PRIMERA VEZ QUE ES POSIBLE DETECTAR LA ACTIVIDAD DE AID MEDIANTE SECUENCIACION MASIVA (PEREZ-DURAN ET AL., 2012). ADEMAS, HEMOS REALIZADO CONTRIBUCIONES RELEVANTES A LA REGULACION DE LOS LINFOCITOS B MEDIADA POR MICRORNAS (DE YEBENES ET AL., 2008, 2010, 2013; BELVER ET AL., 2010, 2011). POR ELLO, CREEMOS QUE LA EXPERIENCIA PREVIA DEL GRUPO HACE QUE LA PROPUESTA SEA VIABLE, TANTO A NIVEL TECNICO COMO CONCEPTUAL._x000D_ _x000D_ LA PROPUESTA SURGE CON EL ESPIRITU DE ABORDAR LOS MECANISMOS MOLECULARES QUE REGULAN LOS CGS PARA ENTENDER EL PROCESO LINFOMAGENICO, Y CON EL FIN ULTIMO DE GENERAR NUEVAS PERSPECTIVAS TERAPEUTICAS PARA ESTAS PATOLOGIAS; POR ELLO EL PROYECTO SE ENCLAVA EN EL RETO DE ¿SALUD, CAMBIO DEMOGRAFICO Y BIENESTAR¿ DE LA ¿ESTRATEGIA ESPAÑOLA DE CIENCIA Y TECNOLOGIA Y DE INNOVACION¿. (Spanish)
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MOST LYMPHOMAS THAT ARE DIAGNOSED IN THE WESTERN WORLD ORIGINATE FROM MATURE B-LYMPHOCYTES THAT HAVE GONE THROUGH GERM CENTER REACTION (GC). CGS ARE STRUCTURES IN WHICH A SOMATIC REMODELING OF IMMUNOGLOBULIN (IG) GENES TAKES PLACE, WHICH ALLOWS THE GENERATION OF HIGH AFFINITY ANTIBODIES AND CONSEQUENTLY IMPROVES THE QUALITY OF THE IMMUNE RESPONSE. ACTIVATION-INDUCED DEAMINASE (AID) INITIATES THESE REMODELING EVENTS DESAMINING CYTOSINS IN THE DNA OF GI GENES. HOWEVER, AID’S SPECIFICITY FOR GI GENES IS NOT PERFECT AND CAN GENERATE CHROMOSOMAL MUTATIONS AND TRANSLOCATIONS AT OTHER SITES OF THE GENOME, ESTABLISHING A DIRECT CONNECTION BETWEEN CGS AND LINFOMAGENESIS. In addition, OTHER MECHANISMS REGULATORS OF CGS, as long as transcriptionals as post-transcriptionals ALSO CONTRIBUTE THE PREDISPOSICATION OF LINFOCITS B TO ONCOGENIC TRANSFORMATION._x000D_ _x000D_ HERE we PROPOSATE THE MOLECULAR MECHANISMS that Regulate the CG Reaction with three SPECIFIC OBJECTIVES: 1) UNDERSTAND THE SPECIFICITY OF AID THROUGH A MASS SEQUENCING APPROACH; 2) Explore the paddle of the CROMATIN CTCF refurbishment in the regulation of AID’s claims and (3) analyse the impact of MIR-28 to the function of the CG and its potential as a therapeutic agent for the treatment of lymphomas._x000D_ _x000D_ THE RECEPTOR LABORATORY had AMPLIA EXPERIENCE IN THE CHANGE OF THE B-LYOLOGY B AND MORE IN THE REGULATION OF AID’S FUNCION (RAMIRO ET AL, 2003, 2004, 2005, 2006; SERNANDEZ ET AL., 2008, BY YEBENES ET AL., 2008), AND HAS RECENTLY SHOWN FOR THE FIRST TIME THAT IT IS POSSIBLE TO DETECT AID’S ACTIVITY BY MASS SEQUENCING (PEREZ-DURAN ET AL., 2012). IN ADDITION, WE HAVE MADE RELEVANT CONTRIBUTIONS TO MICRORNA-MEDIATED B-LYMPHOCYTE REGULATION (DE YEBENES ET AL., 2008, 2010, 2013; BELVER ET AL., 2010, 2011). Therefore, we believe that the preliminary experience of the group makes the proposal moveable, as soon as possible._x000D__x000D__x000D__x000D_ the PROPOSES SURVEY WITH THE SPIRIT to abort the MOLECULAR MECHANISM that govern the CGS to understand the lymphomagic process, and with the end of managing new therapeutics for these pathologies; THAT’S WHY THE PROJECT IS PART OF THE CHALLENGE OF HEALTH, DEMOGRAPHIC CHANGE AND WELL-BEING OF THE SPANISH STRATEGY OF SCIENCE AND TECHNOLOGY AND INNOVATION. (English)
14 October 2021
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Madrid
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Identifiers
SAF2013-42767-R
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