Projektbeschreibung
Bildung und Remodellierung neuronaler Synapsen
Neuronale Synapsen spielen bei der Verarbeitung von Informationen sowie bei der Speicherung und dem Abruf von Erinnerungen eine entscheidende Rolle. Das präsynaptische Kompartiment ist für die Speicherung und Freisetzung von Neurotransmittern verantwortlich. Das postsynaptische Kompartiment wiederum empfängt das Signal und wandelt es in eine Zellantwort um. Das Wissenschaftlerteam des EU-finanzierten Projekts SynapseBuild widmet sich synaptischen Vesikeln, die Neurotransmitter transportieren. Insbesondere möchten die Forschenden mithilfe von verschiedenen innovativen Technologien die Bildung von synaptischen Vesikeln und ihren Transport in den Neuronen näher erforschen. Die Ergebnisse werden die dynamische Remodellierung des präsynaptischen Kompartiments beleuchten und damit eine wesentliche Wissenslücke in der Neurowissenschaft schließen.
Ziel
Our ability to move, to process sensory information or to form, store and retrieve memories crucially depends on the function of neuronal synapses. Synapses comprise a presynaptic compartment harboring the machinery for neurotransmitter release and an associated postsynaptic compartment that processes the neurotransmitter signal. During decades of research we have acquired a wealth of knowledge regarding the mechanisms of neurotransmitter release and information processing in the postsynaptic compartment. In great contrast, we know surprisingly little about the pathways that direct the formation, transport, and assembly of the complex molecular machines that make up a functional presynapse. In particular, it is unclear where and how synaptic vesicle (SV) precursors are formed in the neuronal cell body, in which form they are transported along the axon, and which maturation steps occur to allow their assembly into functional units for neurotransmitter release. How cytoplasmically synthesized presynaptic active zone (AZ) proteins that organize SV release sites are transported and assembled is equally unclear. Here, we combine genome engineering in stem cell-derived neurons and genetically altered mice with proteomic, high-resolution imaging and systems biology approaches to identify the origin and composition of SV and AZ precursors, dissect the mechanisms of their axonal transport and integration into developing synapses and unravel the pathway that controls axonal transport and presynaptic assembly of newly made SV and AZ proteins to set synaptic weight. Our high risk/ high gain studies will yield groundbreaking insights into the mechanisms that mediate the formation, maintenance, and dynamic remodeling of the presynaptic compartment during development and thereby fill a crucial knowledge gap in neuroscience. Furthermore, they may pave the way for the future development of therapeutics to cure nerve injury or neurological disorders linked to synapse dysfunction.
Wissenschaftliches Gebiet
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-ADG - Advanced GrantGastgebende Einrichtung
12489 Berlin
Deutschland