Epigenetic responses to changes in the nuclear redox environment. Possible therapeutic targets in rare diseases. (Q3138350): Difference between revisions
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(Created claim: summary (P836): Physiological levels of reducing agents in the nucleus, such as nuclear glutathione (GSH) and proteins with oxydoreductase activity, protect against oxidative damage related to DNA replication, and also regulate gene expression through processes such as chromatin remodeling, post-transductional modifications in histones and non-coding RNA expression. The purpose of this project is to study the nuclear control mechanisms of the redox environment...) |
(Changed label, description and/or aliases in en: translated_label) |
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Epigenetic responses to changes in the nuclear redox environment. Possible therapeutic targets in rare diseases. | |||
Revision as of 13:01, 12 October 2021
Project Q3138350 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | Epigenetic responses to changes in the nuclear redox environment. Possible therapeutic targets in rare diseases. |
Project Q3138350 in Spain |
Statements
43,750.0 Euro
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87,500.0 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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FUNDACION HOSPITAL CLINICO UNIVERSITARIO DE VALENCIA
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39°28'10.96"N, 0°22'34.82"W
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46250
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Los niveles fisiológicos de agentes reductores en el núcleo, como el glutatión nuclear (GSH) y proteínas con actividad oxidoreductasa, protegen frente al daño oxidativo relacionado con la replicación del ADN, y además regulan la expresión génica mediante procesos como la remodelación de la cromatina, las modificaciones postraduccionales en histonas y la expresión de ARN no codificantes. El propósito del presente proyecto es estudiar los mecanismos nucleares de control del entorno redox que median entre la regulación epigenética y el control de la proliferación, el ciclo celular y el daño al ADN. El análisis detallado de estos procesos y de las interacciones entre las proteínas y moléculas de ARN implicadas, permitirá establecer nuevas interrelaciones que sirvan para el desarrollo de nuevas dianas terapéuticas y ayudarán a definir la etiología de enfermedades complejas que cursen con alteraciones en la proliferación celular y en el estado redox. Para ello, usaremos aproximaciones moleculares y bioquímicas complementadas con estrategias de secuenciación de ARN aplicados sobre diversos modelos celulares, incluyendo células Hela silenciadas para distintos componentes del complejo telomerasa, y fibroblastos procedentes de pacientes con enfermedades progeroides donde se han observado cambios en la estructura de la cromatina (Síndrome de Werner y disqueratosis congénita). Estos modelos nos permitirán contextualizar los resultados obtenidos, en vistas a desarrollar biomarcadores de progresión y gravedad para estas enfermedades minoritarias de gran heterogeneidad fenotípica. (Spanish)
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Physiological levels of reducing agents in the nucleus, such as nuclear glutathione (GSH) and proteins with oxydoreductase activity, protect against oxidative damage related to DNA replication, and also regulate gene expression through processes such as chromatin remodeling, post-transductional modifications in histones and non-coding RNA expression. The purpose of this project is to study the nuclear control mechanisms of the redox environment that mediate between epigenetic regulation and the control of proliferation, cell cycle and DNA damage. The detailed analysis of these processes and of the interactions between the proteins and RNA molecules involved will make it possible to establish new interrelationships that serve to develop new therapeutic targets and will help define the etiology of complex diseases that occur with alterations in cell proliferation and redox state. To do this, we will use molecular and biochemical approaches complemented by RNA sequencing strategies applied to various cell models, including silenced Hela cells for different components of the telomerase complex, and fibroblasts from patients with progeroid diseases where changes in the structure of chromatin (Werner’s syndrome and congenital dyskerratosis) have been observed. These models will allow us to contextualise the results obtained, with a view to developing biomarkers of progression and severity for these minority diseases of great phenotypic heterogeneity. (English)
12 October 2021
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Valencia
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Identifiers
PI16_01031
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