Nanoscale Bioanalytical measurements of Exosome Release to gain insight into the initiation of Short-Term Memory

Ziel

"The aim of this proposed research is to determine the molecular paradigm for initiation of STM based on exosome release. Despite the vital role in neural disorders, the molecular mechanism to initiate STM remains a mystery. Understanding the mysterious mechanism of the STM initiation at the molecular level from how the exosome modulates synaptic strength and plasticity to effect memory is difficult to establish, as it requires advanced analytical measurements at the level of nanometer exosomes and synaptic cleft to monitor individual exosome exocytosis events. ""NanoBioER-STM"" will quantitative measure exosome release at single cell level and clarify it is another pathway of exocytosis through new analytical nanoelectrochemistry (Work Package 1), and will determine how exosome release in the presence of endogenous (lipids and zinc) and exogenous effectors (cognition enhancing drugs) is regulated and will correlate these changes to the molecular initiation of STM (Work Package 2 and 3). These changes, which might alter the cell communication, can be hypothesized to be the initial step that alters synaptic plasticity and commencement of STM. These studies will be developed based on state of the art analytical techniques including subcellular nanoelectrochemistry, Nano Secondary Ion Mass Spectrometry (NanoSIMS) and Stimulated Emission Depletion (STED) super-resolution nanoscopy on model cells and simple animal nerve cells.
Overall, this project will provide new insights into the pathogenesis of neurodegenerative disorders, ultimately driving the development of exosomes as diagnostic biomarkers and therapeutic measures. Implementation of this project will also be a major innovation in the field of both neurochemical research and electrochemical sensing, which will provide innovative analytical approaches for modern brain science discoveries.
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