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H2020Doctoral network2020–2024

NeuroTrans · NEUROtransmitter TRANSporters: from single molecules to human pathologies

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2020-02-01 → 2024-07-31
EU contribution
€3,994,422
Participants
12
Scheme
MSCA-ITN

Lines connect the coordinator with its partners.

Results in brief

NEUROtransmitter TRANSporters: from single molecules to human pathologies

Neurons use electrical signals called action potentials to propagate information along axons and dendrites. In 1936 Otto Loewi received the Nobel Prize in Medicine for the discovery that small molecules (neurotransmitters) are used for inter-neuronal communication. Neuronal signalling requires efficient removal of the released neurotransmitters at synapses, typically achieved through re-uptake by dedicated transporters, the neurotransmitter transporters. Several diseases are associated with improper neurotransmitter clearance (Parkinson’s disease, seizures, anxiety, depression, or schizophrenia). Recreational drugs like cocaine or ecstasy interfere with transport processes and lead to hallucinations, euphoric stimulation, addiction. The vision of the ETN NeuroTrans was to (i) gain an improved understanding on how neurotransmitter transporter dysfunction contributes to neuropsychiatric diseases and how psychoactive substances interfere with normal transporter function and (ii) to establish a robust framework for comprehending the molecular origin of diseases causing mutations. The project’s ultimate objective was to develop a solid model that can predict changes in transporter function from fundamental principles and has defined the following scientific objectives: (i) To obtain kinetic, structural, and mechanics insight into the processes of substrate transport. (ii) To obtain improved electrophysiological, kinetic and thermodynamic data of substrate binding and transport. (iii) To identify the molecular perturbations associated with neuropsychiatric disease. (iv) To identify the mode of action of novel psychoactive substances. (v) To develop or improve instruments and protocols for the quantification of neurotransmitter transporter function. NeuroTrans has established a highly interdisciplinary doctoral training program by forming an interdisciplinary and intersectorial team of world-leading European researchers. Training included most important subdisciplines in quantitative biology, including molecular modelling, computer simulations, biophysics, biochemistry, neurobiology, molecular and structural biology and had a strong industry oriented focus, ensuring that the ESRs can become part of Europe’s future generation of innovative leaders.

Data: CORDIS, © European Union

Project objective

The vision of the ETN network NeuroTrans (NEUROtransmitter TRANSporters: from single molecules to human pathologies) is to (i) enable an improved understanding of how dysfunction of neurotransmitter:sodium symporters (NSS) contributes to neuropsychiatric disease pathobiology and how psychoactive substances target NSS and (ii) to establish a robust framework for comprehending these pathologies through changes in transporter function at the molecular level. The mission of NeuroTrans is to develop a solid model that can predict changes in NSS function using fundamental principles obtained from quantitative experiments using an interdisciplinary approach. NeuroTrans will have a strong translational aspect through the development of enabling techniques in biophysics, molecular and structural biology and through industrial partner which establish novel instruments for use in live cells to quantify kinetics, dynamics and thermodynamic parameters, allowing for exploitation and commercialisation. The NeuroTrans research programme will have major generalizable scientific impact that will be of high relevance to academia, pharmaceutical industry and policy makers and is likely expand not only to other classes of transporters, but to membrane proteins in general.NeuroTrans will establish a highly interdisciplinary doctoral training program by forming an interdisciplinary and intersectorial team of world-leading European researchers. Training will include most important subdisciplines in quantitative biology, including molecular modelling, computer simulations, biophysics, biochemistry, neurobiology, molecular and structural biology. Taining will be headed by an industrial beneficiary to secure a strong industry oriented focus, ensuring that the ESRs can become part of Europe’s future generation of innovative leaders, be at the forefront of science and innovation, translate fundamental research into cutting-edge technologies, and solidify European industry leadership.

Original text from CORDIS.

Participants

  • MEDIZINISCHE UNIVERSITAET WIEN · WienCoordinatorAustria
  • ELVESYS · PARISFrance
  • KOBENHAVNS UNIVERSITET · KOBENHAVNDenmark
  • LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN · PlaneggGermany
  • NANION TECHNOLOGIES GMBH · MUNCHENGermany
  • NANOTEMPER TECHNOLOGIES GMBH · MUNCHENGermany
  • RIJKSUNIVERSITEIT GRONINGEN · GroningenNetherlands
  • UNIVERSIDADE NOVA DE LISBOA · LisboaPortugal
  • UNIVERSITA DEGLI STUDI DELL'INSUBRIA · VareseItaly
  • UNIVERSITAET REGENSBURG · RegensburgGermany
  • UNIVERSITY OF EAST ANGLIA · NorwichUnited Kingdom
  • UNIVERSITY OF HAMBURG · HamburgGermany

Links

Data: CORDIS, © European Union