Q3201482 (Q3201482): Difference between revisions
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(Created claim: summary (P836): The GENERAL OBJECTIVE of the project is to know the molecular elements and mechanisms through which SNPs associated with genetic risk to celiac disease (CE) modify cell phenotypes and contribute to predisposition to the disease. To this end, the following OPERATIVE OBJECTIVES are proposed: — Define the most relevant regulatory elements (expression Quantitative Trait Loci — eQTL) and their target genes (in cis or trans) in isolated cell populat...) |
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The GENERAL OBJECTIVE of the project is to know the molecular elements and mechanisms through which SNPs associated with genetic risk to celiac disease (CE) modify cell phenotypes and contribute to predisposition to the disease. To this end, the following OPERATIVE OBJECTIVES are proposed: — Define the most relevant regulatory elements (expression Quantitative Trait Loci — eQTL) and their target genes (in cis or trans) in isolated cell populations from duodenal biopsies of patients with CD and non-coeliac individuals. — Determine the effect of overexpression/silencement of non-coding regulatory RNAs on the regulation of target genes in response to stimuli (gliadine in intestinal cell lines and PSF in monocytes). — Determine the effect of deletion of active chromatin genomic regions on the regulation of target genes in response to the same stimuli. — Determine the influence of the associated NPS genotypes on this regulation — Characterise the molecular partners of these regulatory elements and draw the molecular mechanism by which they exercise their function, so that early diagnostic biomarkers or potential therapeutic targets for this and other inflammatory diseases can be proposed. METHODOLOGY: 1.- Replication of expression Quantitative Trait Loci (eQTL) with expression studies in human cell populations (epithelial and immunological) isolated from intestinal biopsies of patients and controls. 2.- Experimental validation of confirmed eQTL in cell model cultures (silencement, overexpression or editing of regulatory elements) and molecular characterisation of their molecular partners using RAP and Pull-down. (English) | |||||||||||||||
| Property / summary: The GENERAL OBJECTIVE of the project is to know the molecular elements and mechanisms through which SNPs associated with genetic risk to celiac disease (CE) modify cell phenotypes and contribute to predisposition to the disease. To this end, the following OPERATIVE OBJECTIVES are proposed: — Define the most relevant regulatory elements (expression Quantitative Trait Loci — eQTL) and their target genes (in cis or trans) in isolated cell populations from duodenal biopsies of patients with CD and non-coeliac individuals. — Determine the effect of overexpression/silencement of non-coding regulatory RNAs on the regulation of target genes in response to stimuli (gliadine in intestinal cell lines and PSF in monocytes). — Determine the effect of deletion of active chromatin genomic regions on the regulation of target genes in response to the same stimuli. — Determine the influence of the associated NPS genotypes on this regulation — Characterise the molecular partners of these regulatory elements and draw the molecular mechanism by which they exercise their function, so that early diagnostic biomarkers or potential therapeutic targets for this and other inflammatory diseases can be proposed. METHODOLOGY: 1.- Replication of expression Quantitative Trait Loci (eQTL) with expression studies in human cell populations (epithelial and immunological) isolated from intestinal biopsies of patients and controls. 2.- Experimental validation of confirmed eQTL in cell model cultures (silencement, overexpression or editing of regulatory elements) and molecular characterisation of their molecular partners using RAP and Pull-down. (English) / rank | |||||||||||||||
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| Property / summary: The GENERAL OBJECTIVE of the project is to know the molecular elements and mechanisms through which SNPs associated with genetic risk to celiac disease (CE) modify cell phenotypes and contribute to predisposition to the disease. To this end, the following OPERATIVE OBJECTIVES are proposed: — Define the most relevant regulatory elements (expression Quantitative Trait Loci — eQTL) and their target genes (in cis or trans) in isolated cell populations from duodenal biopsies of patients with CD and non-coeliac individuals. — Determine the effect of overexpression/silencement of non-coding regulatory RNAs on the regulation of target genes in response to stimuli (gliadine in intestinal cell lines and PSF in monocytes). — Determine the effect of deletion of active chromatin genomic regions on the regulation of target genes in response to the same stimuli. — Determine the influence of the associated NPS genotypes on this regulation — Characterise the molecular partners of these regulatory elements and draw the molecular mechanism by which they exercise their function, so that early diagnostic biomarkers or potential therapeutic targets for this and other inflammatory diseases can be proposed. METHODOLOGY: 1.- Replication of expression Quantitative Trait Loci (eQTL) with expression studies in human cell populations (epithelial and immunological) isolated from intestinal biopsies of patients and controls. 2.- Experimental validation of confirmed eQTL in cell model cultures (silencement, overexpression or editing of regulatory elements) and molecular characterisation of their molecular partners using RAP and Pull-down. (English) / qualifier | |||||||||||||||
point in time: 13 October 2021
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Revision as of 00:24, 13 October 2021
Project Q3201482 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | No label defined |
Project Q3201482 in Spain |
Statements
43,250.0 Euro
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86,500.0 Euro
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50.0 percent
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1 January 2017
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31 March 2020
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ASOCIACION INSTITUTO DE INVESTIGACION SANITARIA BIOCRUCES
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43°17'43.73"N, 2°59'24.32"W
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48013
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El OBJETIVO GENERAL del proyecto es conocer los elementos y mecanismos moleculares mediante los que los SNPs asociados con riesgo genético a enfermedad celíaca (EC) modifican los fenotipos celulares y contribuyen a la predisposición a la enfermedad. Para ello, se plantean los siguientes OBJETIVOS OPERATIVOS: - Definir los elementos reguladores más relevantes (expression Quantitative Trait Loci - eQTL) y sus genes diana (en cis o en trans) en poblaciones celulares aisladas de biopsias duodenales de pacientes con EC y personas no celíacas. - Determinar el efecto de la sobreexpresión/silenciamiento de RNAs no codificantes reguladores sobre la regulación de los genes diana en respuesta a estímulos (gliadina en líneas celulares intestinales y LPS en monocitos). - Determinar el efecto de la deleción de regiones genómicas de cromatina activa sobre la regulación de los genes diana en respuesta a los mismos estímulos. - Determinar la influencia de los genotipos de SNPs asociados sobre esta regulación - Caracterizar los socios moleculares de estos elementos reguladores y dibujar el mecanismo molecular mediante el que ejercen su función, de manera que puedan proponerse biomarcadores de diagnóstico temprano o potenciales dianas terapéuticas para ésta y otras enfermedades inflamatorias. METODOLOGÍA: 1.- Replicación de expression Quantitative Trait Loci (eQTL) con estudios de expresión en poblaciones celulares humanas (epitelial e inmunológica) aisladas de biopsias intestinales de pacientes y controles. 2.- Validación experimental de los eQTL confirmados en cultivos de modelos celulares (silenciamiento, sobreéxpresión y/o edición de elementos reguladores) y caracterización molecular de sus socios moleculares mediante RAP y Pull-down. (Spanish)
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The GENERAL OBJECTIVE of the project is to know the molecular elements and mechanisms through which SNPs associated with genetic risk to celiac disease (CE) modify cell phenotypes and contribute to predisposition to the disease. To this end, the following OPERATIVE OBJECTIVES are proposed: — Define the most relevant regulatory elements (expression Quantitative Trait Loci — eQTL) and their target genes (in cis or trans) in isolated cell populations from duodenal biopsies of patients with CD and non-coeliac individuals. — Determine the effect of overexpression/silencement of non-coding regulatory RNAs on the regulation of target genes in response to stimuli (gliadine in intestinal cell lines and PSF in monocytes). — Determine the effect of deletion of active chromatin genomic regions on the regulation of target genes in response to the same stimuli. — Determine the influence of the associated NPS genotypes on this regulation — Characterise the molecular partners of these regulatory elements and draw the molecular mechanism by which they exercise their function, so that early diagnostic biomarkers or potential therapeutic targets for this and other inflammatory diseases can be proposed. METHODOLOGY: 1.- Replication of expression Quantitative Trait Loci (eQTL) with expression studies in human cell populations (epithelial and immunological) isolated from intestinal biopsies of patients and controls. 2.- Experimental validation of confirmed eQTL in cell model cultures (silencement, overexpression or editing of regulatory elements) and molecular characterisation of their molecular partners using RAP and Pull-down. (English)
13 October 2021
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Barakaldo
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Identifiers
PI16_00258
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