Extracellular vesicles will be isolated from frozen blood samples collected from muscle-biopsy participants, as well as from samples collected before and after exercise tests.

Affinity purification methods will be used to obtain extracellular vesicles (EVs) that originated from platelets, brain, and endothelial cells. The protein cargo of these three tissue-specific EV populations will then be characterized by SomaScan analysis. The small RNA content of the EVs will be assessed by RNA sequencing.

Statistical tests will be used to assess: (1) differences between ME/CFS and control protein and RNA cargo within each EV subpopulation; and (2) differences in protein and RNA cargo among EVs from different tissues. A key question is whether EVs from specific ME/CFS tissues, compared with control tissues, differ in the protein pathways represented by their cargoes, indicating dysregulation in the function of those tissues.

We will analyze the protein data to determine how exercise affects the protein cargo of EVs and how proteins and protein networks may differ between patients and controls. Using samples at baseline and following induction of post-exertional malaise will help us learn how the protein content of EVs changes as a result of exercise and their possible involvement in symptoms. We will also be able to correlate findings with data collected from muscle-biopsy participants.

Dr. Ludovic Giloteaux will lead this NIH-funded project (U54AI178855) for analysis of protein cargo, working with Dr. Arnaud Germain and Dr. Katherine Glass in the Hanson lab. He will collaborate with the Grimson lab and Jen Grenier’s group in the Genomics Core for analysis of RNA cargo.

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