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Prenatal Stress Investigation in Cerebral Organoids: a multi-omics study at the level of single cells

Project description

Brain organoids for studying stress responses and mental illness

When an individual encounters a stressful situation, the stress hormone system is activated to initiate a cascade of hormonal and physiological responses that involve cortisol among others. Chronic or prolonged exposure to stress can deregulate the stress hormone system and may lead to mental illness. Funded by the Marie Skłodowska-Curie Actions programme, the PrenatalStressOmics project is interested in studying the molecular mechanisms involved in stress-related mental illnesses. Researchers propose to develop 3D cerebral organoids that mimic the human brain as models of mental illness in the prenatal period. They will analyse transcriptomic and epigenetic changes in response to stress, aiming to delineate the molecular basis of human vulnerability and stress response.

Objective

Mental illnesses affect 25% of the EU population and share increased disease risk through long-term changes to the stress hormone system. These are precipitated as adversities during early life, including the prenatal period. Given the role of stress in causing mental illnesses, it is imperative to learn more about the molecular mechanisms involved. Some progress has been made in elucidating the neurobiology of stress, but many questions cannot be addressed with current tools, which include animal models and 2-dimensional human cell culture systems. This proposal aims to establish 3-dimensional culture systems called cerebral organoids – stem-cell-derived tissues that recapitulate features of the human brain – as research models for developmental psychiatric disturbances. We will focus on glucocorticoids (GCs), some of the primary mediators of stress exposure on the organism, and use organoids as a model of early developing brain. Molecular mechanisms will be compared between ‘stressed’ and ‘unstressed’ conditions, by sequencing the transcriptomes of individual cells. Furthermore, since stress-related disorders are mediated through epigenetic mechanisms, the impact of elevated GC exposure on specific cell types in the cerebral organoid model will be quantified at the epigenome level. These novel and powerful techniques will allow us to deconstruct tissue heterogeneity, elucidating the fine molecular underpinnings of human vulnerability and response to stress. Comparing findings to evidence from longitudinal human cohorts of mothers and their babies who underwent stress during pregnancy will allow placement of findings into the clinical context. This research would pave the way for translation into clinical research, and expedite transitions from basic research to identification of at-risk populations, and even intervention strategies.

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Topic(s)

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Funding Scheme

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2017

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Coordinator

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 171 460,80
Address
HOFGARTENSTRASSE 8
80539 MUNCHEN
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 171 460,80
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