(Part 1 in a series of interviews with researchers investigating novel species for insight into human diseases)
I met Jane when I attended my first meeting of the American Physiological Society with Katie Grabek. Katie was there to present on her study of genomic drivers of hibernation. I was there to network and learn about interesting work was going on in the world of non-model organisms. Since I had recently met and heard talks by the hibernation researchers (we held a conference in SF a few months prior on that very topic), I took the opportunity to check out other sessions. I ended up in a session focused on metabolic disease models and was amazed to hear Jane discuss Northern Elephant Seals (NES’s to their friends) and their extreme metabolic shifts and adaptation to obesity and prolonged fasting, not to mention diving-related hypoxia. She was also pioneering new studies in lipidomics, metabolomics and proteomics in these animals to better understand their biology. I followed up with her after the conference, visiting her lab at UofP and chatting about the overlap in our model systems. I invited her to help us kick off a series of interviews with non-model organism researchers as I think elephant seals make an interesting counterpoint to the research we’re doing at Fauna with 13-lined ground squirrels and other hibernators. Research into these diverse species are providing new insights into potential therapeutic pathways for diseases like obesity, diabetes and other metabolic conditions.
What is unique/special about NES that makes them a key resource for biomedical research?
NES routinely fast from food completely for several months while maintaining extremely high metabolic rates and participating in energetically demanding activities such as reproduction. In contrast, most other animals reduce metabolic costs during fasting via hibernation or torpor. Elephant seals undergo dramatic fattening and fasting without any of the pathologies associated with obesity and rapid weight fluctuations in humans. In addition, fasting seals are hyperglycemic, hyperlipidemic, and insulin-resistant, resembling humans with metabolic syndrome. Their fasting metabolism is almost entirely fat-based but they do not undergo ketoacidosis. Last but not least, elephant seals are elite divers that undergo routine bouts of hypoxia during diving and sleep apneas on land. They appear to have enhanced antioxidant responses and other mechanisms of hypoxia protection that are not yet fully elucidated. Therefore, elephant seal physiology may hold insights into metabolic disease and tissue protection from hypoxia in humans.
What inspired you to start working with marine mammals in general?
As a comparative physiologist, I am especially fascinated by animals that can tolerate extreme environmental and physiological challenges which are lethal to many other species. Marine mammals exhibit some of the most dramatic morphological and physiological adaptations among mammals and offer unparalleled insights into mechanisms that drive convergent evolution on a relatively short time scale (20-50 million years). Some adaptations of marine mammals, such as extreme tolerance to hypoxia and prolonged food deprivation, are uncommon among mammals and challenge established principles of matching metabolic supply and demand. I wanted to use my cell and molecular biology background to examine the molecular basis of marine mammals’ incredible physiological feats.
What is holding the field back?
We are currently unable to conduct many types of functional experiments or any genetic manipulations in elephant seals. However, since elephant seals come ashore on California beaches at predictable times throughout the year and remain on the beach, fasting for up to 4 months, we are able to collect biological samples and conduct metabolic and physiological manipulation experiments (e.g. metabolic tracer studies, hormone infusions). The combination of such organism-level experiments with functional manipulations of seal cells in culture may address these challenges.
How have you seen the research in marine mammals change over the last 5 or 10 years and where is the field going?
The field has been revolutionized by “omics,” especially genome and transcriptome sequencing. We now have a better understanding of the genomic basis of several physiological adaptations in marine mammals. In addition, a better understanding of molecular pathways involved in hypoxia tolerance, fat metabolism, and endocrine regulation of energy homeostasis in laboratory mammals has facilitated comparative studies of these mechanisms in marine mammals.
Where do you see parallels between your work and other "non-model" organism researchers?
I think we struggle with similar challenges, such as the lack of molecular manipulation tools and having to convince funding agencies that research on non-model organisms has scientific and societal value. We also share curiosity about biological diversity and excitement to learn how diverse animals function, especially those that are not well-studied.
What do you wish people understood about the animals you work with?
Marine mammals are protected by federal law and we need permits to do research with them. The experiments that we conduct with wild seals are very challenging, but they would be impossible in many other marine mammal species. We are often limited by the types of tissues we can collect from wild seals and by small sample sizes, which is something that researchers working with traditional model systems don’t always understand.
Latest from Fauna Bio
