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Decoding the 3D chromatin and epigenetic regulation of engram cells in memory and aging

Objective

Memory relies on specialized neuronal ensembles, or engrams, whose activation and silencing shape the encoding, storage, and retrieval of experiences. Recent evidence highlights the role of epigenetic modifications and 3D chromatin architecture in regulating neuronal gene expression, yet how these mechanisms operate within engram cells remains largely unexplored. Understanding these processes is crucial, as epigenetic dysregulation is a hallmark of cognitive impairment and neurodegeneration and memory function declines with age. This project aims to provide the first integrative characterization of transcriptional, epigenetic and structural genome features of hippocampal engram cells across different stages of memory processing and aging. I will use the novel NucTRAP2 genetic model that allows precise tagging of behaviorally defined neuronal ensembles for which transcriptional characterization is available, and collect immunoGAM (a cutting-edge ligation-free 3D genome mapping technique), ATAC-seq and CUT&Tag. This integrateive approach will enable unprecedented insights into chromatin accessibility, histone modifications, and higher-order genome folding in distinct engram populations in the context of memory formation. Comparative analyses between young and aged mice will identify chromatin remodeling and epigenetic states associated with engram silencing and memory decline. By bridging behavioral neuroscience with advanced epigenomics and 3D genome technologies, this fellowship will generate a unique multi-layered map of gene regulation in engrams. The findings will provide fundamental knowledge on memory biology and aging, while equipping the candidate with a highly competitive multidisciplinary skill set.

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Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC)
Net EU contribution
€ 202 125,12
Address
ROBERT ROSSLE STRASSE 10
13125 Berlin
Germany
Region
Berlin Berlin Berlin
Activity type
Research Organisations
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Total cost
No data

Partners (1)