We hypothesize that simulated microgravity will lead to linkage-specific alterations in skeletal muscle sialylation mediated by changes in sialidases and/or sialyltransferases. To address this, we will use immunofluorescence with a panel of SA-detecting lectins, glycanbinding proteins, as well as lectin microarrays, to probe alterations in linkage-specific SA abundance in skeletal muscle tissue from rats with or without a hindlimb-unloading protocol. Next, we will probe expression of the sialyltransferases that form SA linkages and the sialidases that enzymatically remove them, via qRT-PCR and Western blotting to assess the underlying mechanism of these SA alterations and identify novel pharmacological targets.

This will be the first study to address alterations in skeletal muscle sialylation in the context of spaceflight-induced muscle atrophy. This would inform future studies to assess rescue of sialylation in skeletal muscle as a treatment for atrophy, as skeletal muscle sialylation can be altered via oral supplementation and gene therapy; in fact, sialylation-altering nutraceutical therapies for skeletal muscle disease have recently progressed through clinical trials for the rare disease GNE myopathy. This work aims to develop novel targets to address skeletal muscle atrophy via nutraceutical and pharmacological approaches, which would help to ensure effective performance of flight mission tasks.