New technologies for in situ measurement of exosome release from brain slice cultures

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Abstract Our research program aims to understand the role of extracellular lipid vesicles in intercellular communication, with the ultimate goal of elucidating new mechanisms of communication involved in disease pathologies. To achieve this, we are developing new bioanalysis tools including tissue culture and perfusion systems for sampling exosomes released from ex vivo tissue slices, and separations-based bioassays for the direct and selective quantitation of exosomes in microfluidic volumes. For the next 5 years, our program goals are: 1) to achieve key system refinements of our tissue culture perfusion system that will enable high sensitivity measurements of secreted factors; 2) to develop a novel mode of separations-based immunoassay tailored specifically to the quantitation of exosome release; and 3) to apply these technologies to investigate a hypothesis of circadian rhythm coordination via extracellular vesicle release in the suprachiasmatic nucleus of the brain. We envision that our research will enable new dimensions of study in the bioanalytical and extracellular vesicle research communities, ultimately leading to new therapies that target dysregulated intercellular communications in neurological and metabolic disorders.