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Single Cell PTSD: Novel Target Identification

Project description

Understanding PTSD for better treatment

Post-traumatic stress disorder (PTSD) affects around 4 % of people worldwide. Treatment options are limited, and research has been constrained by challenges such as small sample sizes, slowing progress in understanding the condition. The ERC-funded sc-PTSD project aims to explore PTSD pathology using single-nuclei RNA sequencing, DNA methylation profiling, and 3D chromatin structure analysis. It aims to identify cellular and transcriptional changes in post-mortem brains, uncover molecular targets, and characterise traditional PTSD models through genomics. The project will also develop a novel humanised model for PTSD, test the efficacy of new and existing targets to reduce PTSD in mice, and ultimately enhance our understanding of PTSD for better interventions.

Objective

Post-traumatic stress disorder (PTSD) is a devastating psychiatric disease triggered by severe psychological trauma, affecting 4% of the global population - a prevalence projected to rise due to ongoing conflicts like the war in Ukraine and the looming threat of climate change. Despite its widespread impact, we lack effective treatments of PTSD, placing a significant burden on individuals and society.

Previous PTSD research was hindered by limitations such as bulk tissue analyses, a lack of epigenetic focus, or small sample sizes. These drawbacks limit our understanding of cell-type-specific alterations during PTSD. My proposed project will leverage single-nuclei RNA sequencing, DNA methylation profiling, and 3D chromatin structure analysis to achieve unprecedented insights into PTSD pathology.

Specifically, I aim to:

1) Identify cellular, epigenetic, and transcriptional perturbations in a post-mortem human brain PTSD cohort, revealing promising molecular targets.

2) Characterize classical models of PTSD using single-nuclei genomics, and develop novel humanized model of PTSD. This will enable the identification of the most relevant model for human PTSD, and streamline further validation of targets.

3) Test the efficacy of novel as well as already identified targets from my pilot animal study by utilizing epigenome-modifying tools to alleviate PTSD pathology in mouse models.

This project will deepen our understanding of PTSD at unprecedented resolution, ultimately validating novel molecular targets and paving the way for more effective interventions in future.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

(opens in new window) ERC-2025-STG

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Host institution

RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG
Net EU contribution
€ 1 403 931,00
Address
SEMINARSTRASSE 2
69117 Heidelberg
Germany
Region
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 403 931,00

Beneficiaries (2)