Project description
Trace amine-associated receptor 1 as a new molecular target in schizophrenia investigation
The study of the functional role of striatal dopamine (DA) signalling is necessary due to its wide-ranging impact on learning, motivational and motor processes. DA over-reactivity is the most well-established pathophysiological mechanism underlying schizophrenia. The EU-funded TACtIK project aims to introduce an innovative chemogenetic/positron emission tomography (PET) imaging model of striatal DA over-reactivity to test the efficacy of new antipsychotic compounds that target the trace amine-associated receptor 1 (TAAR1). The goal is to develop a mouse model of increased pre-synaptic DA synthesis capacity (Ki) in the striatum and to determine if TAAR1 agonists decrease striatal Ki in the model and in patients with a diagnosis of schizophrenia.
Objective
My research plan aims at generating an innovative chemogenetic/positron emission tomography (PET) imaging translational model of striatal dopamine (DA) over-reactivity, the most well-established pathophysiological mechanism underlying schizophrenia. I will use this platform to test the therapeutic efficacy of antipsychotic compounds with a totally new mechanism of action, i.e. targeting the trace amine-associated receptor 1 (TAAR1). Pre-clinical findings will have immediate translation to humans. I envisage a two-fold utility of this platform for the scientific community: 1) development of innovative therapeutic strategies for psychotic disorders; 2) ask fundamental questions about the pathophysiology of schizophrenia.
A substantial share of patients treated with available antipsychotics do not respond and/or experience undesirable side effects. Available antipsychotics do not target the neurobiological mechanisms underlying schizophrenia symptoms, i.e. increased pre-synaptic DA synthesis capacity (Ki) in the striatum. They rather rely on blockade of DA receptors post-synaptically, possibly causing iatrogenic DA super-sensitivity. Therefore, there is a quest for improved therapeutic strategies, addressing DA over-reactivity. A novel target is represented by TAAR1, a G protein-coupled receptor that has been found to crosstalk with the DAergic system. Based on these premises, the objectives of this project are:
-Work package 1. To develop a chemogenetic translational mouse model of increased striatal Ki. We will use [18F]-FDOPA PET imaging to determine if selective manipulation of midbrain neuron firing increases Ki.
-Work package 2. To determine if TAAR1 agonists (TAAR1 toolbox) decrease striatal Ki in the model from WP1. We will ascertain whether TAAR1 is necessary for the effect on Ki, using TAAR1 knock-out (KO) mice.
-Work package 3. To determine whether TAAR1 toolbox modulate Ki in patients with a diagnosis of schizophrenia, applying [18F]-FDOPA PET imaging.
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.
- engineering and technology medical engineering diagnostic imaging computed tomography
- medical and health sciences clinical medicine psychiatry schizophrenia
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Keywords
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)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2020
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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.
SW7 2AZ London
United Kingdom
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.