Objective
Elucidation of the chemistry of learning processes in defined brain areas would clarify the role neurotransmitters are playing in the chemical background of memory imprinting and substantially contribute to the treatment of memory related neurological diseases. Targeted, timely and continuous monitoring of neurotransmitters in defined brain areas before and after imprinting stimuli is not possible using electrodes based on today's classical design and chemical approach..
The proposed project targets design and development of microbiosensors based on chemically engineered oxidases, their miniaturisation and application for timely monitoring of neurotransmitters studied during a learning process caused by external stimuli in an existing animal model. The new microbiosensors will be based on chemically engineered enzymes with improved characteristics, and will be miniaturised and designed in a shape which will enable localised mapping of defined brain areas for neurotransmitter detection. Combining the expertise of the involved four research groups the following main multidisciplinary tasks will accomplished:
Chemical engineering of FAD-containing enzymes by directed binding of transitional metal complexes to the surface of the enzyme in the vicinity of the active site, and/or direct binding of the same mediating metal complexes to the FAD cofactor, using a novel coordination approach. Enzymatic and electrochemical characterisation of the engineered FAD-containing oxidases.
Integration of engineered enzymes in various biosensor configurations Miniaturisation of the optimal biosensor configuration (needle type electrodes) and their micropositioning in model systems Neurotransmitter monitoring in memory related neurobiological experiments correlating neurotransmitter release/change in concentration with imprinting stimuli.
The chemically engineered enzyme molles synthesised using a novel coordination chemistry approach are expected to display improved enzymatic and electrochemical characteristics, such as, low detection limit, fast electron transfer rate, short response time, etc. The new needle type design of the developed and optimised microbiosensors will enable their accurate positioning and thus monitoring of local changes in neurotransmitter release. Applying these microelectrodes for brain analysis, relevant information are anticipated hopefully revealing a possible correlation between the changes in neurotransmitter concentration before and after stimuli. Accumulated knowledge will not only elucidate the chemical background of recognition memory-linked neurobiological processes, but also substantially contribute to envisaged treatment of various neurodegenerative diseases strongly correlated with altered signalling in defined brain areas.
Topic(s)
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22100 Lund
Sweden