Descripción del proyecto
Revelación de la arquitectura de las proteínas sinápticas en la salud y la enfermedad
La transmisión de información neuronal en el encéfalo se produce a través de estructuras especializadas llamadas sinapsis. Las sinapsis contienen más de dos mil proteínas distintas, y su organización espacial, arquitectura y red de interacción se han cartografiado muy poco. Los científicos de la iniciativa SynLink, financiada con fondos europeos, tienen como objetivo desarrollar una fuente de espectrometría de masas con entrecruzamiento para el análisis estructural del proteoma sináptico. El método de SynLink permitirá identificar las reestructuraciones y alteraciones de la red sináptica que ocurrendurante el aprendizaje y la memoria. Es importante destacar que puede servir para estudiar la disfunción sináptica, que subyace a diversos trastornos psiquiátricos y neurológicos.
Objetivo
Brain function crucially depends on chemical neurotransmission at synapses, while, conversely, synaptic dysfunction underlies neurological and psychiatric disorders. Synapses are composed of more than 2,000 distinct proteins, spatially organized into specialized molecular machineries. During decades of efforts, researchers have acquired a wealth of knowledge on individual key components of the synapse. However, the overall picture of the spatial arrangement, molecular architecture and interaction network of the synaptic proteome remains largely uncharted. Furthermore, innovative methods that allow system-wide profiling of these organizational aspects of synaptic proteins are in great demand.
I propose to develop a highly sensitive cross-linking mass spectrometry (XL-MS) pipeline to analyze structural and organizational features of the synaptic proteome at an unprecedented depth and comprehensiveness. In parallel, I also plan to establish quantitative XL-MS strategies to reveal global network rearrangements and complex-specific alterations during long-term potentiation, which arguably is the most attractive cellular model for learning and memory. Importantly, it is foreseeable that numerous novel insights can be discovered, for which I will use complementary approaches and tools, such as biochemistry, super-resolution imaging, structural modelling and network analysis to validate and interrogate their molecular details and network principles. These studies will yield groundbreaking insights into the molecular architecture of the synapse and thereby fill a crucial knowledge gap in neuroscience. Furthermore, they will provide a framework to gain a deeper understanding of the dynamic regulation in synaptic plasticity and synaptic dysfunction in neurological disorders.
Ámbito científico
- natural sciencesbiological sciencesneurobiology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomics
- medical and health sciencesclinical medicinepsychiatry
- natural sciencesphysical sciencesopticsmicroscopysuper resolution microscopy
- natural scienceschemical sciencesanalytical chemistrymass spectrometry
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
12489 Berlin
Alemania