(Part 2 in a series of interviews with researchers investigating novel species for insight into human diseases)
Featuring: Frank van Breukelen - Associate Professor of Biological Sciences, Univ. of Nevada, Las Vegas
You don’t have to chat with Frank van Breukelen long to get him talking about tenrecs and before long, about why he “despises” them. “Tenrecs are just weird, they don’t follow the rules” he’ll sigh over drinks. However, he’s devoted his career to unraveling their strange behavior and modes of hibernation, with the goal of understanding fundamental truths of how mammals (including ourselves) control metabolic rate. Frank was one of ten hibernation researchers who joined us at the Fauna Bio headquarters for our “Burrow-to-Bedside” conference in September of 2018 as we wrapped up our time in the Age1 accelerator. He is currently a Fauna Bio collaborator and we are working to understand more about how tenrecs resist hypoxia as well as working with other groups to build a better reference sequence for the common tenrec (Tenrec ecaudatus).
A bit about tenrecs themselves: they look like hedgehogs or shrews, but are in reality more closely related to aardvarks and elephants than hedgehogs, being a member of the Afrotherian mammals. Given that Frank has worked with everything from 13-lined ground squirrels to pupfish in his research career, we wanted to find out more about why he had picked tenrecs as a focus and what we can learn from these bizarre mammals.
What is unique/special about tenrecs that makes them a key resource for biomedical research?
Tenrecs are very poorly understood mammals that have some bizarre features like a cloaca (one common opening rather than separate anal and urogenital openings), a really small and poorly developed brain, which may even lack a functional corpus callosum, the part of the brain which communicates between the hemispheres, and other features that suggest they might be reminiscent of an early placental mammal ancestor. Understanding how they hibernate and comparing that to the more advanced model of ground squirrel hibernation can teach us what has to change or evolve if an animal is to be a good hibernator.
What inspired you to start working with these creatures in general?
Barry Lovegrove gave a talk where he showed that this small hibernator didn't do interbout arousals. [Author note: Interbout arousals are a period of time where deep hibernators increase their temperatures from near freezing to normal in a matter of hours before descending again into deep hibernation] I thought interbout arousals were essential to reset homeostasis. I thought that if we simply put tenrecs at lower temperatures, they'd arouse and we'd have a great model for understanding what causes arousals. Tenrecs turned out to have a novel form of hibernation wherein they're constantly torpid during the Austral winter but may be more or less torpid depending on season and temperature. Tenrecs can hibernate at temperatures of 28°C which allows us to study temperature regulation distinct from hibernation status. In other words, it's a much more complicated system but tenrecs promise to be able to elucidate fundamental questions that have eluded the hibernation community for decades.
What is holding the field back?
So little is known about tenrecs that we're having to do all of the work that was done 50 years ago in ground squirrels. We'd like to get into more of the biochemistry and 'omics but it's taken us this long to figure out what to sample. We think we still have gaps in our sampling scheme e.g. oxygen consumption may vary by as much as 25 fold in resting tenrecs. We can't pick up on that in our sampling scheme yet although we're designing experiments now that might help do that.
How have you seen the research in these and other hibernators (or non-model species) change over the last 5 or 10 years and where is the field going?
If you had asked me if bears hibernated 10 years ago, I would have said absolutely not. Bears denned. There were big differences in body temperature (a really cold bear will have a body temp of ~31°C) and organ function (kidneys still work and sows give birth while hibernating!). There was simply no way that bears denning was comparable to ground squirrels hibernating. With our increased appreciation of the weird hibernators like tenrecs, elephant shrews, the marsupials, and lemurs, I now think of hibernation as more of a continuum. On one end we have the ground squirrels with their amazing ability to depress metabolism and on the other side we have sleeping humans with little to no energetic savings. In that context, I think we need to think a little more about what sleep accomplishes outside of simple energetics (the restorative properties) and figure out how that fits into the hibernation paradigm vis-'a-vis homeostatic tuning, etc.
How have you seen the research in these and other hibernators (or non-model species) change over the last 5 or 10 years and where is the field going?
If you had asked me if bears hibernated 10 years ago, I would have said absolutely not. Bears denned. There were big differences in body temperature (a really cold bear will have a body temp of ~31°C) and organ function (kidneys still work and sows give birth while hibernating!). There was simply no way that bears denning was comparable to ground squirrels hibernating. With our increased appreciation of the weird hibernators like tenrecs, elephant shrews, the marsupials, and lemurs, I now think of hibernation as more of a continuum. On one end we have the ground squirrels with their amazing ability to depress metabolism and on the other side we have sleeping humans with little to no energetic savings. In that context, I think we need to think a little more about what sleep accomplishes outside of simple energetics (the restorative properties) and figure out how that fits into the hibernation paradigm vis-'a-vis homeostatic tuning, etc.
Where do you see parallels between your work and other "non-model" organism researchers?
When we first received the tenrecs, we expected them to do what ground squirrels do. Our experiments were geared towards ideas of the almost binary status of ground squirrels. Squirrels are either torpid or aroused (or going in between). Tenrecs can be more or less torpid while still being active. It was a weird concept for us. When we accepted tenrecs weren't ground squirrels, we were able to start making more accurate predictions of how tenrecs work. We predicted that even active tenrecs could have varying levels of homeostasis. Active tenrecs can vary how much kidney function they perform. Now, I think I understand ground squirrel hibernation more. For me, hibernation is suspending homeostasis. In ground squirrels, there are two states. One (torpid) in which virtually everything is messed up homeostatically and the other (interbout aroused) in which homeostatic processes are well coordinated. In tenrecs, torpor and active states represent a continuum of homeostatic function.
What do you wish people understood about the animals you work with?
Nothing is easy with tenrecs. The animals are so bizarre that even simple things like pulling blood becomes complex (requires us to surgically install vascular access ports). Even basic husbandry takes us ~6 h per day during the active season. The variability of tenrecs' basic physiological responses is amazing. This past spring, we did a collaborative project wherein there were a few tenrecs that experienced reduced O2 consumption and body temperatures when injected with norepinephrine. Most tenrecs did what one would normally expect but they're tenrecs- tenrecs exist to confuse the bejesus out of us.
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