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IMMUNE-GENEMEMO

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Identification of transcriptional memory maintenance factors through a cell sele...

Identification of transcriptional memory maintenance factors through a cell selection strategy Memory of gene expression states is essential for development and maintenance of tissues. Chromatin, a protein DNA complex, is implicated in the process. Local, chromatin feedback loops are involved in maintenance of gene silencin... ver más

31/05/2024

252K€

Presupuesto del proyecto: 252K€

Líder del proyecto

UNIWERSYTET GDANSKI No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

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Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2024-05-31

MSCA-IF-2020: Individual Fellowships

I+D

Cerrada hace 4 años

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3 Participantes

252.08K€ | Lider

THE GENERAL HOSPITAL CORPORA...

177.27K€ | Participante

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Duración del proyecto: 37 meses Fecha Inicio: 2021-04-16
Fecha Fin: 2024-05-31

Líder del proyecto

UNIWERSYTET GDANSKI No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 252K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Memory of gene expression states is essential for development and maintenance of tissues. Chromatin, a protein DNA complex, is implicated in the process. Local, chromatin feedback loops are involved in maintenance of gene silencing, but analogous mechanisms for preservation of active states are unknown. In order to reveal feedback loops for active gene expression states it is crucial to uncouple them from ongoing transcription, as it occurs in the case of maintenance of silent states. Such partition takes place during trained immunity – memory of the innate immune system. A key paradigm is interferon gamma (IFNγ) stimulation. While IFNγ induces many genes, a subset of those is maintained in a poised, inactive state that allows for rapid re-activation at a later time – an event called transcriptional memory. In my ongoing research I have discovered novel genes that show strong transcriptional memory of prior IFNγ activation and have obtained initial mechanistic insights into the role of chromatin in the process. Importantly, I discovered that memory results in a larger proportion of cells expressing the target gene. This forms the basis of a cell sorting, high throughput assay that I have developed. I am now in a unique position to capitalize on those discoveries and tools. I aim to identify novel transcriptional memory maintenance factors in human cells using an unbiased approach based on an efficient cell selection strategy combined with genome wide, CRISPR-Cas9 mutagenesis protocols. Secondly I wish to establish the function of the identified components in the stability of dendritic cells identity after differentiation form monocytes. The multidisciplinary and unique perspective of this project: combining gene expression analysis and selection strategies with immunological expertise will advance our understanding of the mechanisms underlying maintenance of gene expression states and contribute to the development of new immune therapies and vaccines.

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