ANALYSIS OF VIRULENCE AND PATHOGENICITY MECHANISMS IN MYCOPLASMAS: DESIGN OF VACCINES AGAINST SOME SPECIES OF CLINICAL INTEREST (Q3160298): Difference between revisions
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(Created claim: summary (P836): MYCOPLASMAS REPRESENT ONE OF THE SIMPLEST KNOWN BIOLOGICAL SYSTEMS AND ARE A GOOD MODEL OF MINIMO GENE AND MINIMA-REPLICATIVE CELL. DESPITE ITS SIMPLICITY, ITS BASIC BIOLOGY IS VERY UNKNOWN AND HAS A LARGE NUMBER OF GENES WITHOUT FUNCTIONAL ANNOTATION. MOST MYCOPLASMAS ARE PARASITES AND PATHOGENS OF VARIOUS ANIMAL SPECIES, INCLUDING THE HUMAN SPECIES. THE FUNDAMENTAL OBJECTIVE OF THIS PROJECT IS TO DESIGN STRATEGIES FOR THEIR PROPHYLAXIS OR THER...) |
(Changed label, description and/or aliases in en: translated_label) |
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ANALYSIS OF VIRULENCE AND PATHOGENICITY MECHANISMS IN MYCOPLASMAS: DESIGN OF VACCINES AGAINST SOME SPECIES OF CLINICAL INTEREST | |||
Revision as of 16:37, 12 October 2021
Project Q3160298 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | ANALYSIS OF VIRULENCE AND PATHOGENICITY MECHANISMS IN MYCOPLASMAS: DESIGN OF VACCINES AGAINST SOME SPECIES OF CLINICAL INTEREST |
Project Q3160298 in Spain |
Statements
105,875.0 Euro
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211,750.0 Euro
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50.0 percent
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1 January 2014
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31 December 2017
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UNIVERSIDAD AUTONOMA DE BARCELONA
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41°29'27.71"N, 2°8'15.00"E
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08266
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LOS MICOPLASMAS REPRESENTAN UNO DE LOS SISTEMAS BIOLOGICOS MAS SIMPLES CONOCIDOS Y SON UN BUEN MODELO DE ¿GENOMA MINIMO¿ Y ¿CELULA MINIMA¿ AUTORREPLICATIVA. PESE A SU SIMPLICIDAD, SU BIOLOGIA BASICA ES MUY DESCONOCIDA Y PRESENTAN UN GRAN NUMERO DE GENES SIN ANOTACION FUNCIONAL. LA MAYORIA DE LOS MICOPLASMAS SON PARASITOS Y PATOGENOS DE DIVERSAS ESPECIES ANIMALES, INCLUYENDO LA ESPECIE HUMANA. EL OBJETIVO FUNDAMENTAL DEL PRESENTE PROYECTO ES DISEÑAR ESTRATEGIAS PARA SU PROFILAXIS O TERAPIA, ESPECIALMENTE TRATANDO DE OBTENER VACUNAS CONTRA ALGUNOS MICOPLASMAS. CONCRETAMENTE NOS CENTRAREMOS EN LAS SIGUIENTES ESPECIES: MYCOPLASMA GENITALIUM, PATOGENO DEL SISTEMA UROGENITAL HUMANO; MYCOPLASMA HYOPNEUMONIAE, IMPORTANTE PATOGENO RESPIRATORIO DEL GANADO PORCINO; MYCOPLASMA BOVIS, IMPORTANTE PATOGENO RESPIRATORIO DEL GANADO BOVINO; MYCOPLASMA HYORHINIS, PATOGENO DEL GANADO PORCINO Y TAMBIEN AFECTA A HUMANOS (RELACIONADO CON EL CANCER DE PROSTATA). M. GENITALIUM ES LA ESPECIE QUE PREVIAMENTE MAS HEMOS ESTUDIADO, EN GRAN PARTE POR SU MAYOR FACILIDAD DE TRANSFORMACION Y MANIPULACION GENETICA EN GENERAL Y POR TRATARSE DE UN MODELO DE GENOMA MINIMO. NOS HA PERMITIDO ADQUIRIR EXPERIENCIA EN EL MANEJO Y MANIPULACION GENETICA DE ESTOS DIFICILES MICROORGANISMOS ASI COMO EN ANALIZAR LOS MECANISMOS DE PATOGENICIDAD DE LOS MICOPLASMAS E IDENTIFICAR Y CARACTERIZAR (EN ALGUNOS CASOS A NIVEL DE ESTRUCTURA CRISTALOGRAFICA) LAS PROTEINAS INVOLUCRADAS EN LOS MISMOS. EN ESTE CASO, MAS QUE UNA VACUNA CREEMOS INTERESANTE RASTREAR LA ACTIVIDAD INHIBIDORA DE UNA LIBRERIA DE COMPUESTOS DESARROLLADOS EN EL ANTERIOR PROYECTO COORDINADO Y DIRIGIDOS A INACTIVAR LAS GLICOSIL-TRANSFERASAS DEL MICROORGANISMO. ALGUNAS DE ESTAS ENZIMAS SON TOTALMENTE INDISPENSABLES PARA MICOPLASMA Y EXHIBEN ACTIVIDADES MUY ESPECIFICAS, POR LO QUE SON BUENAS CANDIDATAS A DIANAS TERAPEUTICAS. ADEMAS, SEGUIREMOS ESTUDIANDO LAS BASES MOLECULARES DE SU PATOGENICIDAD, IDENTIFICANDO GENES DE VIRULENCIA ESPECIALMENTE AQUELLOS RELACIONADOS CON EL MECANISMO DE ADHESION Y REDES COMPLEJAS DE REGULACION GENICA. TAMBIEN SE REANOTARA SU GENOMA EN BASE A UN ANALISIS PROTEOGENOMICO Y BIOINFORMATICO, REANOTACION QUE SERA EXTENSIBLE A LOS GENES ORTOLOGOS DE OTRAS ESPECIES DE MICOPLASMAS. EN EL CASO DE M. HYOPNEUMONIAE Y M. BOVIS TRATAREMOS DE DISEÑAR UNA VACUNA VIVA POR DELECION DE GENES DE VIRULENCIA ASI COMO UTILIZAR LA CELULA VIVA VACUNAL COMO HUESPED PARA UNA POSIBLE VACUNA COMBI, POR EXPRESION HEREROLOGA DE PROTEINAS ANTIGENICAS DE OTROS PATOGENOS PORCINOS (P.E., CIRCOVIRUS) Y BOVINOS (P.E., BHV-1, BRSV, ETC) RESPECTIVAMENTE. ESTO REQUIERE DISPONER DE METODOS DE TRANSFORMACION, COSA QUE YA HEMOS CONSEGUIDO EN M. HYOPNEUMONIAE Y QUE SE VA A EXTENDER A M. BOVIS, CON ANTECEDENTES QUE INDICAN QUE PODRIA SER TRANSFORMADO MEDIANTE TRANSPOSICION Y RECOMBINACION HOMOLOGA. FINALMENTE, EN EL CASO DE M. HYORHINIS, AUNQUE YA SE HA MENCIONADO SU PAPEL COMO PATOGENO, EN EL PRESENTE PROYECTO VAMOS A EXPLORAR OTRA FACETA DEL MISMO. RECIENTEMENTE SE ACABA DE DESCRIBIR QUE ALGUNA/S DE SUS PROTEINAS DE MEMBRANA PRESENTA ACTIVIDAD ANTIAGREGACION DE LOS BETAPEPTIDOS DEL ALZHEIMER. ESTE EFECTO VENDRIA MEDIADO POR UNA SOBREEXPRESION DEL GEN DE LA CALPASTATINA (INHIBIDOR DE LA CALPAINA) EN LAS CELULAS HUMANAS. TRATAREMOS DE PURIFICAR, IDENTIFICAR Y CARACTERIZAR ESTE O ESTOS COMPONENTES Y DE REALIZAR ENSAYOS EN UN MODELO DE RATON, DISPONIBLE EN OTRO GRUPO DE NUESTRA UNIVERSIDAD, CON OBJETO DE IDENTIFICAR EL MECANISMO SUBYACENTE. (Spanish)
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MYCOPLASMAS REPRESENT ONE OF THE SIMPLEST KNOWN BIOLOGICAL SYSTEMS AND ARE A GOOD MODEL OF MINIMO GENE AND MINIMA-REPLICATIVE CELL. DESPITE ITS SIMPLICITY, ITS BASIC BIOLOGY IS VERY UNKNOWN AND HAS A LARGE NUMBER OF GENES WITHOUT FUNCTIONAL ANNOTATION. MOST MYCOPLASMAS ARE PARASITES AND PATHOGENS OF VARIOUS ANIMAL SPECIES, INCLUDING THE HUMAN SPECIES. THE FUNDAMENTAL OBJECTIVE OF THIS PROJECT IS TO DESIGN STRATEGIES FOR THEIR PROPHYLAXIS OR THERAPY, ESPECIALLY BY TRYING TO OBTAIN VACCINES AGAINST SOME MYCOPLASMAS. SPECIFICALLY, WE WILL FOCUS ON THE FOLLOWING SPECIES: MYCOPLASMA GENITALIUM, PATHOGEN OF THE HUMAN UROGENITAL SYSTEM; MYCOPLASMA HYOPNEUMONIAE, IMPORTANT RESPIRATORY PATHOGEN IN PIGS; MYCOPLASMA BOVIS, AN IMPORTANT RESPIRATORY PATHOGEN IN CATTLE; MYCOPLASMA HYORHINIS, PATHOGEN OF PIGS AND ALSO AFFECTS HUMANS (RELATED TO PROSTATE CANCER). M. GENITALIUM IS THE SPECIES THAT WE HAVE PREVIOUSLY STUDIED MOST, LARGELY FOR ITS GREATER EASE OF TRANSFORMATION AND GENETIC MANIPULATION IN GENERAL AND BECAUSE IT IS A MODEL OF A MINIMAL GENOME. IT HAS ALLOWED US TO GAIN EXPERIENCE IN THE GENETIC MANAGEMENT AND MANIPULATION OF THESE DIFFICULT MICROORGANISMS AS WELL AS IN ANALYSING THE PATHOGENICITY MECHANISMS OF MYCOPLASMAS AND IDENTIFYING AND CHARACTERISING (IN SOME CASES AT THE LEVEL OF CRYSTALOGRAMIC STRUCTURE) THE PROTEINS INVOLVED IN THEM. IN THIS CASE, RATHER THAN A VACCINE, WE THINK IT INTERESTING TO TRACK THE INHIBITORY ACTIVITY OF A LIBRARY OF COMPOUNDS DEVELOPED IN THE PREVIOUS COORDINATED PROJECT AND AIMED AT INACTIVATING THE GLYCOSYLTRANSFERASE OF THE MICROORGANISM. SOME OF THESE ENZYMES ARE TOTALLY INDISPENSABLE FOR MYCOPLASMA AND EXHIBIT VERY SPECIFIC ACTIVITIES, SO THEY ARE GOOD CANDIDATES FOR THERAPEUTIC TARGETS. IN ADDITION, WE WILL CONTINUE TO STUDY THE MOLECULAR BASES OF ITS PATHOGENICITY, IDENTIFYING VIRULENCE GENES ESPECIALLY THOSE RELATED TO THE ADHESION MECHANISM AND COMPLEX NETWORKS OF GENIC REGULATION. YOUR GENOME WILL ALSO BE REANOTATED BASED ON A PROTEOGENOMIC AND BIOINFORMATIC ANALYSIS, REANOTATION THAT WILL BE EXTENDED TO THE ORTHOLOGOUS GENES OF OTHER MYCOPLASMA SPECIES. IN THE CASE OF M. HYOPNEUMONIAE AND M. BOVIS WE WILL TRY TO DESIGN A LIVE VACCINE BY DELETION OF VIRULENCE GENES AS WELL AS USE THE LIVE CELL AS A HOST FOR A POSSIBLE COMBI VACCINE, BY EXPRESSION HEREROLOGY OF PROTEINS ANTIGENICAS OF OTHER PORCINE PATHOGENS (P.E., CIRCOVIRUS) AND CATTLE (P.E., BHV-1, BRSV, ETC.) RESPECTIVELY. THIS REQUIRES HAVING METHODS OF TRANSFORMATION, WHICH WE HAVE ALREADY ACHIEVED IN M. HYOPNEUMONIAE AND THAT WILL BE EXTENDED TO M. BOVIS, WITH A HISTORY THAT INDICATES THAT IT COULD BE TRANSFORMED BY TRANSITION AND HOMOLOGATION. FINALLY, IN THE CASE OF M. HYORHINIS, ALTHOUGH HIS ROLE AS A PATHOGEN HAS ALREADY BEEN MENTIONED, IN THIS PROJECT WE WILL EXPLORE ANOTHER FACET OF IT. RECENTLY, IT HAS JUST BEEN DESCRIBED THAT SOME OF ITS MEMBRANE PROTEINS HAVE ACTIVITY ANTIAGREGACION OF ALZHEIMER’S BETAPEPTIDS. THIS EFFECT IS MEDIATED BY AN OVEREXPRESSION OF THE CALPASTATIN GENE (CALPAIN INHIBITOR) IN HUMAN CELLS. WE WILL TRY TO PURIFY, IDENTIFY AND CHARACTERISE THIS OR THESE COMPONENTS AND CARRY OUT TRIALS ON A RATON MODEL, AVAILABLE IN ANOTHER GROUP OF OUR UNIVERSITY, IN ORDER TO IDENTIFY THE UNDERLYING MECHANISM. (English)
12 October 2021
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Cerdanyola del Vallès
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Identifiers
BIO2013-48704-R
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