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HEIndividual fellowship2022–2024

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

Horizon Europe — Marie Skłodowska-Curie Actions

Duration
2022-09-01 → 2024-08-31
EU contribution
€222,728
Participants
1
Scheme
HORIZON-TMA-MSCA-PF-EF

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Results in brief

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

In NanoBioER-STM, I describe completely novel approaches aimed at completely novel goals to measure how metabolites are packaged across nanometer organelles (vesicles, stress granules), while simultaneously pinpointing their location in live cells. I will then determine how molecular species move dynamically between organelle subcompartments in and interchange between organelles. Finally, I will use these analytical methods to examine organelles in the neurons of advanced systems, develop a model of their interactions, and create a unified theory of how organelles regulate plasticity. These are unexplored areas of nanobio chemical science as the analytical methods to pursue these goals do not yet exist. I aim to develop new methods to determine metabolites and precursors including neurotransmitters such as catecholamines, but also reactive oxygen species and their interplay, all with nanometer precision. This will allow me to define the processes that are regulating the cell and plasticity as well as controlling disease at the level of chemical interactions between organelles. The objectives are as follows: Objective 1. Determine stress granules from single cells and to confirm its electroactive content in SGs. 1-1 Determination of ex-vivo separated SGs and confirm ROS in SGs. 1-2 Determination of SG in single cells. 1-3 Evaluation of the method in Objective 1-2. Objective 2. Determine the changes in cell membrane lipids involved in the ROS dynamics of SGs leading to STM 2-1 Determination of ROS dynamics in single cell. 2-2 Selection of effective lipid model. 2-3 Measure the localization of designated lipids. Objective 3. Test the effects of SGs on plasticity of neuro cells. 3-1 Lipids and zinc as the chemical effectors in short-term plasticity. 3-2 Measurement of the effect of cognition enhancing drugs on SGs dynamics. 3-3 Cognition enhancing drugs on lipid composition and zinc. 3-4 Effects of SGs on vesicles in neuro cells.

Data: CORDIS, © European Union

Project objective

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.""

Original text from CORDIS.

Participants

  • GOETEBORGS UNIVERSITET · GoeteborgCoordinatorSweden

Links

Data: CORDIS, © European Union