HOMEOSTASIA AND MOLECULAR REPLACEMENT IN THE CENTRAL DOGMA: PROTHEOMIC APPROACHES, RESPONSE TO STRESS AND CONTRIBUTION OF THE PREFOLDIN-LIKE BUD27/URI COMPLEX (Q3201538)
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Project Q3201538 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | HOMEOSTASIA AND MOLECULAR REPLACEMENT IN THE CENTRAL DOGMA: PROTHEOMIC APPROACHES, RESPONSE TO STRESS AND CONTRIBUTION OF THE PREFOLDIN-LIKE BUD27/URI COMPLEX |
Project Q3201538 in Spain |
Statements
135,520.0 Euro
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169,400.0 Euro
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80.0 percent
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30 December 2016
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29 June 2021
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UNIVERSIDAD DE JAEN
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37°57'20.63"N, 3°29'31.42"W
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23050
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EL ENFOQUE REDUCCIONISTA DE LA BIOLOGIA MOLECULAR HA APORTADO UNA GRAN CANTIDAD DE INFORMACION SOBRE LOS MECANISMOS CELULARES, PERO SU RESULTADO ES DEMASIADO LIMITADO PARA ENTENDER COMO FUNCIONA UNA CELULA EN SU CONJUNTO. SE REQUIERE UNA VISION INTEGRADORA QUE DESCUBRA LOS NIVELES SUPERIORES DE RELACION ENTRE MOLECULAS, RUTAS Y ESTRUCTURAS CELULARES. LAS CIENCIAS OMICAS Y LA BIOLOGIA DE SISTEMAS PROPORCIONAN LAS HERRAMIENTAS Y LA VISION GLOBAL NECESARIA PARA CAPTAR LAS PROPIEDADES EMERGENTES DE LA CELULA. DESDE ESA PERSPECTIVA, QUEREMOS CONTRIBUIR A RE-EXAMINAR LA EXPRESION GENICA, ENTENDIENDO POR TAL EL PROCESO QUE CONVIERTE LA INFORMACION GENETICA EN ELEMENTOS FENOTIPICOS ACTIVOS (PROTEINAS). _x000D_ EN EL PARADIGMA CLASICO, EL EQUILIBRIO DINAMICO DE LOS ELEMENTOS DE LA CELULA (HOMEOSTASIA) SE CONSIGUE GRACIAS AL BALANCE ENTRE SINTESIS Y DEGRADACION, CON MECANISMOS DE CONTROL QUE REGULAN UNO DE ESOS DOS PROCESOS. SEGUN ESA VISION, EL LLAMADO ¿DOGMA CENTRAL¿ ES UN CAMINO LINEAL EN EL QUE EL MRNA JUEGA UN PAPEL DE MERO INTERMEDIARIO. EN LOS ULTIMOS AÑOS NUESTRO EQUIPO HA CONTRIBUIDO A DEMOSTRAR QUE EXISTE UN CONTROL GENERAL DE LA CONCENTRACION CELULAR DE MRNA (HOMEOSTASIA DEL MRNA) EN SACCHAROMYCES CEREVISIAE QUE ES FRUTO DE LA COMUNICACION CRUZADA ENTRE LAS MAQUINARIAS DE TRANSCRIPCION Y DEGRADACION (MRNA-CROSSTALK). ESTA IMPLICA TANTO LA IMPRONTA QUE LOS MRNAS RECIBEN EN SU SINTESIS, COMO LA RETROALIMENTACION QUE SOBRE LA MAQUINARIA DE TRANSCRIPCION EJERCEN LOS PROPIOS FACTORES DE DEGRADACION DEL MRNA. DURANTE EL PROYECTO EN CURSO HEMOS IDENTIFICADO LA ETAPA DE ELONGACION DE LA TRANSCRIPCION, Y MAS CONCRETAMENTE EL FENOMENO DE MARCHA ATRAS DE LA RNA POLIMERASA II (RNAPII BACKTRACKING), COMO UN ELEMENTO CLAVE DEL MRNA-CROSSTALK. HEMOS DEMOSTRADO ASIMISMO QUE LAS TASAS DE TRANSCRIPCION Y DEGRADACION DE MRNA CAMBIAN DE FORMA PARALELA CON LA VELOCIDAD DE PROLIFERACION CELULAR, MANTENIENDO CONSTANTE LA CONCENTRACION DE MRNA PARA UNA MAYORIA DE GENES. COMO CONSECUENCIA DE ELLO, ES EL RECAMBIO DE MRNA (MRNA-TURNOVER) LO QUE VARIA CON LA PROLIFERACION PARA GARANTIZAR SU HOMEOSTASIA. _x000D_ EN EL PRESENTE PROYECTO QUEREMOS PROFUNDIZAR EN EL CONOCIMIENTO DEL MRNA-CROSSTALK, IDENTIFICAR LOS MECANISMOS QUE ACOPLAN EL MRNA-TURNOVER A LA TASA DE PROLIFERACION CELULAR, MODELAR MATEMATICAMENTE ESTE ACOPLAMIENTO Y COMPROBAR SI TAMBIEN TIENE LUGAR EN LAS CELULAS HUMANAS. QUEREMOS ASIMISMO EXPLORAR LA POSIBLE EXISTENCIA DE COMUNICACION CRUZADA ENTRE LA TRADUCCION DE LOS MRNAS A PROTEINAS Y LA DEGRADACION DE ESTAS (PROTEIN-CROSSTALK). NUESTROS DATOS PRELIMINARES ASI LO SUGIEREN Y, CASO DE DEMOSTRARLO, QUEREMOS ENTENDER LOS MECANISMOS QUE LO SUSTENTAN Y EXPLORAR SI TAMBIEN EXISTE UN ACOPLAMIENTO DEL RECAMBIO DE PROTEINAS (PROTEIN-TURNOVER) A LA PROLIFERACION CELULAR. POR ULTIMO QUEREMOS EXPLICAR LA PARTICIPACION EN EL PROCESO DE ELONGACION TRANSCRIPCIONAL DE LAS PREFOLDINAS, UNAS CO-CHAPERONAS QUE TRABAJAN EN EL PLEGAMIENTO DE ACTINAS Y TUBULINAS DURANTE EL ENSAMBLAJE DEL CITOESQUELETO. LOS RESULTADOS DEL PROYECTO EN CURSO INDICAN QUE CONTRIBUYEN A LA DINAMICA TRANSCRIPCIONAL DE LAS HISTONAS A TRAVES DE REMODELADORES DE CROMATINA QUE CONTIENEN ACTINA. QUEREMOS ENTENDER ESE MECANISMO Y COMPROBAR SI LAS PREFOLDINAS ESTAN MEDIANDO LA COMUNICACION ENTRE LA DINAMICA CITOPLASMICA Y LA EXPRESION DE LOS GENES. EN DEFINITIVA, ESTE PROYECTO PRETENDE INVESTIGAR TRES FENOMENOS DE HOMEOSTASIA MOLECULAR QUE LA VISION REDUCCIONISTA DEL DOGMA CENTRAL NO HA PERMITIDO ENTENDER. (Spanish)
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THE REDUCTIONIST APPROACH TO MOLECULAR BIOLOGY HAS PROVIDED A LOT OF INFORMATION ABOUT CELLULAR MECHANISMS, BUT ITS RESULT IS TOO LIMITED TO UNDERSTAND HOW A CELL AS A WHOLE WORKS. AN INTEGRATIVE VISION IS REQUIRED THAT DISCOVERS THE HIGHER LEVELS OF RELATIONSHIP BETWEEN MOLECULES, PATHWAYS AND CELLULAR STRUCTURES. THE OMIC SCIENCES AND SYSTEMS BIOLOGY PROVIDE THE TOOLS AND THE GLOBAL VISION NEEDED TO CAPTURE THE EMERGING PROPERTIES OF THE CELL. FROM THAT PERSPECTIVE, WE WANT TO CONTRIBUTE TO RE-EXAMINING THE GENIC EXPRESSION, UNDERSTANDING BY SUCH THE PROCESS THAT TURNS GENETIC INFORMATION INTO ACTIVE PHENOTYPIC ELEMENTS (PROTEINS). _x000D_ in CLASSIC PARADIGMA, THE DINAMIC EQUILIBRIUM OF CELULA ELEMENTS (homeostasia) THANKS TO THE BALANCE ENTRE SINTESIS AND DEGRADATION, WITH CONTROL MECHANISMS OF THIS PROCEDURES. ACCORDING TO THAT VISION, THE SO-CALLED CENTRAL DOGMA IS A LINEAR PATH IN WHICH MRNA PLAYS A ROLE AS A MERE INTERMEDIARY. IN THE LAST FEW YEARS OUR TEAM HAS HELPED TO DEMONSTRATE THAT THERE IS A GENERAL CONTROL OF MRNA CELL CONCENTRATION (MRNA HOMEOSTASIA) IN SACCHAROMYCES CEREVISIAE WHICH IS THE RESULT OF CROSS COMMUNICATION BETWEEN THE TRANSCRIBING AND DEGRADATION MACHINERY (MRNA-CROSSTALK). THIS IMPLIES BOTH THE IMPRINT THAT MRNAS RECEIVE IN THEIR SYNTHESIS, AND THE FEEDBACK ON THE TRANSCRIPTION MACHINERY EXERTED BY THE MRNA’S OWN DEGRADATION FACTORS. DURING THE ONGOING PROJECT WE HAVE IDENTIFIED THE STAGE OF TRANSCRIPTION ELONGATION, AND MORE SPECIFICALLY THE MARCH PHENOMENA BEHIND RNA POLYMERASE II (RNAPII BACKTRACKING), AS A KEY ELEMENT OF MRNA-CROSSTALK. WE HAVE ALSO SHOWN THAT MRNA TRANSCRIPTION AND DEGRADATION RATES CHANGE PARALLEL WITH CELL PROLIFERATION VELOCITY, MAINTAINING CONSTANT MRNA CONCENTRATION FOR A MAJORITY OF GENES. AS A RESULT, IT IS THE REPLACEMENT OF MRNA (MRNA-TURNOVER) THAT VARIES WITH THE PROLIFERATION TO GUARANTEE ITS HOMEOSTASY. _x000D_ in the present project we want to develop in the knowledge of MRNA-crosstalk, identify the mechanisms that link the MRNA-TURNOVER to the CELL PROLIFERATION tax, mathematically MODELING THIS ACOPLAMITING AND COMPROBATING WHICH YOU HAVE TO PLACE IN HUMAN CELLS. WE ALSO WANT TO EXPLORE THE POSSIBLE EXISTENCE OF CROSS-COMMUNICATION BETWEEN THE TRANSLATION OF MRNAS TO PROTEINS AND THE DEGRADATION OF PROTEINS (PROTEIN-CROSSTALK). OUR PRELIMINARY DATA SUGGEST THIS AND, IF PROVEN, WE WANT TO UNDERSTAND THE MECHANISMS THAT SUPPORT IT AND EXPLORE WHETHER THERE IS ALSO A LINK BETWEEN PROTEIN REPLACEMENT (PROTEIN-TURNOVER) AND CELL PROLIFERATION. FINALLY, WE WANT TO EXPLAIN THE PARTICIPATION IN THE PROCESS OF TRANSCRIPTIONAL ELONGATION OF THE PREFOLDINS, SOME CO-CHAPERONAS THAT WORK IN THE FOLDING OF ACTINS AND TUBULINS DURING THE ASSEMBLY OF THE CYTOSKELETON. THE RESULTS OF THE ONGOING PROJECT INDICATE THAT THEY CONTRIBUTE TO TRANSCRIPTIONAL DYNAMICS OF HISTONES THROUGH CHROMATIN REMODELERS CONTAINING ACTIN. WE WANT TO UNDERSTAND THIS MECHANISM AND CHECK IF PREFOLDINS ARE MEDIATING THE COMMUNICATION BETWEEN CYTOPLASMIC DYNAMICS AND GENE EXPRESSION. IN SHORT, THIS PROJECT AIMS TO INVESTIGATE THREE PHENOMENA OF MOLECULAR HOMEOSTASIA THAT THE REDUCTIONIST VISION OF THE CENTRAL DOGMA HAS NOT ALLOWED TO UNDERSTAND. (English)
13 October 2021
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Jaén
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Identifiers
BFU2016-77728-C3-2-P
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