Our work is focused on studying the molecular mechanisms of neurotransmitter release. We are interested in the role of alternate SNAP isoforms, namely SNAP-29 and SNAP-47, in the different phases leading to the fusion of vesicles with the plasma membrane. We are also interested in studying how these proteins may interact/compete with the dominant isoforms, and with the calcium sensor proteins for release triggering, and how that affects the dynamics of exocytosis. On the other hand, these proteins have been implicated in synaptic plasticity processes and genetic studies found links to human cognitive disorders, namely schizophrenia. Therefore, we also want to generate and characterize genetically modified mice lacking their expression in order to look for new disease models. We use mainly electrophysiology techniques (whole-cell patch-clamp, membrane capacitance measurements, amperometry), molecular biology and optical techniques (calcium uncaging, calcium microfluorimetry).

Some planned projects:

Elucidate the molecular mechanisms of alternate SNAP contribution to the vesicle fusion process

The exocytosis machinery is composed, at its bare minimum, by the SNARE complex, made up of the proteins SNAP-25, syntaxin and synaptobrevin, and by a calcium sensor, typically one synaptotagmin, that initiates the membrane merger process. There are, however, alternate isoforms of these proteins whose possible functions in the process of fusion and transmitter release remain unstudied. We intend to approach this question by making use of molecular biology and electrophysiology to elucidate, in particular, the roles of SNAP-29 and SNAP-47 in the processes of vesicle docking, priming and fusion. We also want to understand the possible assembly of these isoforms into SNARE complexes and with alternate synaptotagmin isoforms.

Generation and behavioral characterization of possible novel genetic mouse models for neuropsychiatric diseases

Several recent studies have identified changes in SNAP-29 gene copy number or genetic polymorphisms in human patients suffering from schizophrenia. We therefore intend to generate and behaviorally characterize KO mice for SNAP-29, in order to seek for traits of this disease that may allow using these animals as novel experimental models. We also intend to generate and characterize KO mice for SNAP-47 to study possible phenotypes related to neuropsychiatric diseases, with special focus on schizophrenia and autism. The mice will also be a target of detailed electrophysiological characterization.