Background
In animals, the most efficient way of producing energy (ATP) is through aerobic (oxygen demanding) metabolism in the mitochondria, but this option is not available without oxygen. Therefore, anoxia will soon lead to energy failure and death. Moreover, reintroduction of oxygen release reactive oxygen species (ROS), which rapidly damage cells and eventually lead to cell death even if they survived the initial anoxic period. A major source of ROS in re-oxygenation is succinate dehydrogenase (SDH, complex II in the electron transport chain), which goes in reverses due to the build-up of succinate during anoxia. Contrary to many other animals, the crucian carp (Carassius carassius) maintains ATP production in anoxia using anaerobic metabolism (primarily glycolysis). We have preliminary data indicating little oxidative damage after anoxia and re-oxygenation in the crucian carp tissues (liver, heart, brain) (Fig. A), and that mitochondria from crucian carp produce less ROS than the anoxia intolerant common carp (Cyprinus carpio) (Fig. B). Still, our recent metabolomics studies show accumulation of succinate in all tissues (Fig. C), although lower than mice but higher than in anoxia tolerant freshwater turtles. Intriguingly succinate is accumulating to a larger extent in the crucian carp plasma (blood) and the liver compared to brain and heart. We hypothesise that crucian carp circumvents the succinate-driven ROS production, by shuttling the succinate away from sensitive tissues, either into the water, or that it is metabolized in the liver, an organ where high constitutive activity of enzymes involved in the protection of cells from oxidative damage by ROS was observed (like catalase, Fig. D).
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Master project
Gene and protein expression of succinate transporters (e.g. solute carrier family 13 member 3, SLC13A3; monocarboxylate transporter 1, MCT1) will be measured using qPCR and Western blot, respectively, in the gills and other tissues, from crucian carp exposed to anoxia and re-oxygenation. Exposure of the fish will be carried out by other members of the research group, since conducting these experiments requires the “Course In Animal Research In Norway” (CareIn, 8 ECTS). The master student can observe and aid with tissue sampling, and will do the rest of the lab work.
Supervisors and research group
Main supervisor will be Lucie Gerber (FYSCELL) with co-supervision by Sjannie Lefevre (FYSCELL) and Göran Nilsson (FYSCELL) from the Adaptations – Lefevre-Nilsson group (https://www.mn.uio.no/ibv/english/research/sections/fyscell/groups/adaptations-nilsson/index.html). The project is part of the of the convergence environment “Availability and function of donor organs: Debating the dead donor rule (3DR)” (https://www.uio.no/english/research/strategic-research-areas/life-science/research/convergence-environments/3dr/). Lucie is using ribosomal footprint profiling to identify mechanisms of interest in the crucian carp liver and heart, and also has an interest in mitochondria and ROS. Sjannie is interested in the molecular mechanisms of tolerance to anoxia and in particular re-oxygenation in crucian carp, and also the evolution of anoxia tolerance, while Göran recently has worked on the mechanisms of ethanol production.
Are you interested? Contact Lucie (lucie.gerber@ibv.uio.no) or Sjannie (s.l.nilsson@ibv.uio.no) and ask for a meeting.