Collaborative Research: Role of Endothelial Cell Activation in Hypoxia Tolerance of an Elite Diver, the Weddell Seal

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This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2). Part I: Non-technical description: The Weddell seal is an iconic Antarctic species and a superb diver, swimming down to 2,000 feet and staying underwater for up to 45 minutes. However, as for any mammal, the low oxygen concentrations in the blood during diving and the recovery once back at the surface are challenges that need to be overcome making their diving ability something unique that has fascinated scientists for decades. This research project will evaluate the underlying processes in Weddell seal’s physiology that protects this species from the consequences of diving. The work will combine laboratory experiments where cells that line the blood vessels will be exposed to conditions of low oxygen, similar to those that will be measured in diving seals in Antarctica. The investigarors will test a new idea that several short-term dives, performed before a long dive, allows seals to condition themselves. Measurements on the chemical compounds released to the blood during dives, combined with experiments on the genes that regulate them will provide clues on the biochemical pathways that help the seals tolerate these extreme conditions. The project allows for documentation of individual seal dives and provisioning of such information to the broader science community that seeks to study these seals, educating graduate and undergraduate students and a post-doctoral researcher and producing a science-outreach comic book for middle-school students to illustrate the project's science activities, goals and outcomes. Part II: Technical description: 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 knochout 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. Expert collaborators will provide field support, with the ice camp, dive hole for the seals, and telemetry associated with the seals’ dives. The project builds upon previous NSF-funded projects where the seal genome and cellular resources were produced. Undergraduate researchers will be recruited from institutional programs with a track record of attracting underrepresented minorities and a minority-serving institution. To further increase polar literacy training and educational impacts, the field team will include a blog where field experiences are shared and comic book preparation with an artist designed for K-12 students and public outreach.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.