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The spatial organization of gene regulation in embryonic development.
Master transcription factors (TFs) cooperate with chromatin in regulating genomic activity in animal development and stress response. Local clustering of TFs into dense, sub-micrometer size condensates is emerging as a key feature... Master transcription factors (TFs) cooperate with chromatin in regulating genomic activity in animal development and stress response. Local clustering of TFs into dense, sub-micrometer size condensates is emerging as a key feature of transcriptional regulation. This includes intranuclear condensates formed by pioneer TFs during development, transient clusters of RNA Polymerase II complex and nuclear stress bodies formed during a heat shock. Despite the ubiquity of these assemblies, we know little about the biophysical mechanism of their formation or physiological function. The last years have seen the development of new frameworks to study such transient assemblies, including various types of phase transitions and tools to probe and modulate them. However, this work has been limited mainly to cell culture and in vitro experiments that failed to incorporate the vital role of chromatin in organizing gene regulation. I propose a cross-disciplinary strategy consisting of a novel in vitro assays and functional studies in a nematode Caenorhabditis elegans to study the spatial organization of transcription in embryonic development and stress response. The specific aims are: 1. Understand the physiological relevance of transcriptional condensates in animal development and stress response. 2. Determine the molecular composition and regulators of transcriptional condensates. 3. Dissect the mechanism of transcriptional condensate formation using a novel chromatin carpet assay. We will use state-of-the-art microscopy-based tools to investigate the formation and function of nuclear condensates in developing animal embryos and develop innovative assays to probe the condensation of TFs on the surface of purified native chromatin. The obtained results will provide an unprecedented insight into the composition, assembly mechanism, and physiological relevance of biomolecular condensates formed by the transcriptional apparatus during differentiation and stress response. ver más
31/01/2028
NENCKI
2M€
Perfil tecnológico estimado
Duración del proyecto: 61 meses Fecha Inicio: 2022-12-08
Fecha Fin: 2028-01-31

Línea de financiación: concedida

El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2022-12-08
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-2022-STG: ERC STARTING GRANTS
Cerrada hace 2 años
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
INSTYTUT BIOLOGII DOSWIADCZALNEJ IM. M. NENCK... No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5