Willkommen auf der Homepage des Sonderforschungsbereichs 1286 Willkommen auf der Homepage des Sonderforschungsbereichs 1286 Outeiro, Tiago Fleming, Prof. Dr.

Representative fluorescence images of primary hippocampal neurons cultured in vitro for 15 days.
Neurons are stained in green (MAP2), synapsin are stained in red and nuclei are stained with DAPI (blue).

Outeiro, Tiago Fleming, Prof. Dr.

Representative fluorescence images of primary astrocytes cultured in vitro for 15 days.
GFAP-positive cells are stained in green and nuclei are stained with DAPI (blue).

Summary

Synapses are the central information processors in the brain. Their function, efficacy and plasticity are key determinants of all brain functions, and of the corresponding behavioral output. Conversely, aberrant synapse function is the cause of many neurological and psychiatric disorders. Our ultimate objective is to generate a functional virtual synapse, in silico, that covers both the presynaptic and postsynaptic compartments.

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RESEARCH INFRASTRUCTURE

This CRC 1286 builds on extensive infrastructure that has been built over the last decade by many institutions,...

DETAILS

... ranging from the Excellence Initiative to measures promoted by the German Research Foundation (DFG), the German Ministry for Education and Research (BMBF), the Max Planck Society, and the State of Lower Saxony.

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TEAM MEMBERS

Our Team consists of 24 principal investigators and one worker of coordination.

DETAILS

They are Scientists of different institutions in the region of Göttingen and join forces with each other for research purposes.

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PROJECTS

The CRC 1286 works interdisciplinary (see research Infrastructure). It is divided into 3 research areas.

DETAILS

Project area A – C, one associated and three central projetcs support our research to take some more steps towards future.

Progress of research

We will start by determining the molecular composition of the synapse, and its changes during synaptic activity. We will determine the locations of synaptic organelles and proteins, their copy numbers, their post-translational modifications, and their interactions. We will focus on two classical models, hippocampal cultures and synaptosomes, which are ideal for imaging and biochemical studies, respectively. Together with analyses of synaptic lipids and RNAs, these parameters will serve to generate a structural model of an averaged synapse at rest, during activity, and after activity. We will complement this model with several key functional parameters, ranging from synaptic protein mobility to the principles behind the formation of synaptic active zones. The structural and functional parameters will be integrated in modeling studies aiming to explain and predict synaptic function and plasticity. At the same time, we will initialize analyses of a limited number of synaptic disease models, to decipher the quantitative differences that separate the pathologically altered synapses from normal ones. We will thereby test the hypothesis that specific synaptic diseases are caused by differences in the numbers, activity and/or organization of defined synaptic elements.

3D Model of a Synapse

The movie displays a rotating example of a rat neuronal synapse with differing sets of protein types.
The synaptic membrane types comprise the plasma membrane, 375 vesicles, 7 endosomes and one mitochondrion.
They were modeled from membrane coordinates of several layers. The number and location of 62 different protein types were analyzed so that they could be placed accordingly inside the synaptic cytosol and on the synaptic membranes. In total, the protein count reaches 300,000.

THE NANOSCALE DYNAMICS OF PROTEINS IN THE SYNAPTIC BOUTON

Eine Standbildansicht der Proteinbewegung neben dem synaptischen A still view of the protein motion next to the synaptic vesicle cluster. Each molecule is color-coded according to its diffusion coefficient in the place of its current location. Darker violet colors indicate lower diffusion coefficients.

A view of soluble protein movement in the synapse. Only synaptic vesicles (grey shapes) and soluble proteins are shown, the plasma membrane surrounding the synapse is transparent. Each colored shape is a single protein molecule, with the molecules of the same protein type having the same color and shape.

laboratory of Prof. Silvio Rizzoli

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