Collaborative Research: Role of Endothelial Cell Activation in Hypoxia Tolerance of an Elite Diver, the Weddell Seal
The Weddell seal is a champion diver with high natural tolerance for low blood oxygen concentration (hypoxemia) and inadequate blood supply (ischemia). The processes unique to this species protects their tissues from inflammation and oxidative stress observed in other mammalian tissues exposed to such physiological conditions. This project aims to understand the signatures of the processes that protect seals from inflammation and oxidant stress, using molecular, cellular and metabolic tools. Repetitive short dives before long ones are hypothesized to precondition seal tissues and activate the protective processes. The new aspect of this work is the study of endothelial cells, which sense changes in oxygen and blood flow, providing a link between breath-holding and cellular function. The approach is one of laboratory experiments combined with 2-years of field work in an ice camp off McMurdo Station in Antarctica. The study is structured by three main objectives: 1) laboratory experiments with arterial endothelial cells exposed to changes in oxygen and flow to identify molecular pathways responsible for tolerance of hypoxia and ischemia using several physiological, biochemical and genomic tools including CRSPR/Cas9 knockout and knockdown approaches. 2) Metabolomic analyses of blood metabolites produced by seals during long dives. And 3) Metabolomic and genomic determinations of seal physiology during short dives hypothesized to pre-condition tolerance responses. In the field, blood samples will be taken after seals dive in an isolated ice hole and its diving performance recorded. It is expected that the blood will contain metabolites that can be related to molecular pathways identified in lab experiments.
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