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Brainwave-Discovery, SynSys and the synapse

In neurological diseases, things go wrong at the synapse. Diseases from mental retardation to neurodegeneration are linked to defects of synapse function. The synapse is a small organelle with about 2000 proteins, which is strongly conserved through evolution. We are using the conserved Drosophila synapse as a simple system in which to assess how functional differences between variants of human synaptic proteins cause changes in synapse function and disease. The fruit fly can make a special contribution due to simpler molecular biology, a rich toolkit for its genetic manipulation and the sheer time and cost effectiveness of the system compared to mammalian models.

Brainwave-Discovery is taking part in a Europe-wide programme (Synaptic Systems or SynSys), which has the aim of molecular analysis and dynamic modelling of synaptic protein complexes, with a focus on the major excitatory synapse that uses Glutamate as a neurotransmitter. SynSys aims to produce a blueprint for rational strategies to therapies for human brain diseases.

A direct route is to focus right now on synaptic proteins that can be linked to disease by human genetics, or which are likely to be involved in learning and memory, which are easily measurable in Drosophila. We have selected a first group of 50 human proteins to be studied on this basis, for some of which there are mouse models for data comparison.

The first stage, which has been completed, is to clone and express each human protein in the fly brain and check for behavioural phenotypes and brain anatomy. Where it occurs, expression of the equivalent fly protein is suppressed, and the effectiveness of the human protein as a substitute is studied.

The full power of the Drosophila system is felt when we move on to real disease model building - small networks of interacting human proteins running in the fly brain, and the comparison of multiple variant forms of human proteins that are correlated in human genetics with disease.

We can select normal, neurodegenerative disease (Alzheimer's, Parkinson's, Huntington's) or custom backgrounds for all models.

Watch this space for an ever increasing set of synaptic disease models in which to test your compounds. We give priority to proteins chosen by customers. For more information check out our website or contact info@brainwave-discovery.com

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