Project description
Schizophrenia models unveil therapeutic biomarkers
Schizophrenia is a mental disorder associated with a perturbed interpretation of reality and patients experience hallucinations and delusions. As it is not possible to stratify schizophrenia patients, they all receive antipsychotic drugs as a first-line treatment with suboptimal results. Funded by the Marie Skłodowska-Curie Actions programme, the MapGen project aims to delineate the neuronal pathways responsible for schizophrenia pathophysiology. Researchers will develop neurodevelopmental models from patient stem cells and investigate their molecular and genetic profile. Results will also help understand the different response to treatment among schizophrenia patients, paving the way for more tailored interventions.
Objective
Schizophrenia (SCZ) affects 20 million people worldwide and antipsychotics remain the only effective pharmacological intervention. However, one-third of people with SCZ do not respond to first-line antipsychotic drugs. In the absence of clinical biomarkers to stratify SCZ subtypes, all individuals receive the same initial intervention, and it takes >4 years on average before people with resistant forms of the condition receive suitable treatment.
My overall aim is to unravel the pre-symptomatic cell-type-specific genetic circuits contributing to differential treatment response in SCZ. To achieve my aim I will use an interdisciplinary approach that improves my technical and soft skills and further extends my international network through a two-year stay at Yale University, and three months secondment at Harvard Medical School. During the return phase, I will establish myself as an independent researcher and a suitable candidate for leadership of a to-be-established stem cell lab at the host institute.
Objectives are (O1) to identify cell-type-specific neuronal pathways associated with distinct neurotransmission imbalances in each SCZ subgroup using a human-based neurodevelopmental model. (O2) To determine the functional link between SCZ-associated risk variants and response to antipsychotics.
Method: I will couple advanced stem cell models (region-specific brain organoids) with single-cell RNA sequencing to generate cell-type-specific transcriptomic profiles of patient-derived brain organoids from treatment-responsive and treatment-resistant forms of SCZ. I will integrate the potential risk variants from SCZ-GWAS and use published functional genomics data to determine the genetic pathways and associated regulators implicated in the etiopathophysiology of differential response to antipsychotics.
Impact: identify distinct genetic makeup for each SCZ subgroup to serve as potential predictive biomarkers and points of therapeutic intervention.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences medical biotechnology cells technologies stem cells
- natural sciences biological sciences genetics RNA transcriptomes
- medical and health sciences clinical medicine psychiatry schizophrenia
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-GF - HORIZON TMA MSCA Postdoctoral Fellowships - Global Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2021-PF-01
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5021 Bergen
Norway
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