A Journey With Jellyfish: Understanding Sleep In Brainless Animals

I find myself working in an emerging field that may be called ecological evolutionary developmental and behavioral biology, which involves analyzing biological phenomena within a broader context.  We try to understand how evolution programs the capabilities of an organism based on its environmental needs, and how those abilities may be similar or different from those seen in other animals.  More specifically, I focus on better understanding the self-repair and behavioral capabilities of a very early branching animal lineage, and I have worked on two basic questions: 1) How do animals regain function after injury, and 2) How fundamental is the sleep behavior?

I did not start graduate school with these questions in mind, but instead, my research naturally led me to them. I began at Caltech as a microbiologist, but my now thesis advisor Lea Goentoro and I would occasionally meet and discuss all sorts of topics, and we found we shared many research interests.  One project we had in mind was to better understand the reversible aging seen in the “immortal jellyfish” Turritopsis dohrnii, and I began working in her lab in the spring of 2013.

Lea is a systems biologist with a background working with Xenopus laevis, the African clawed frog; beginning with jellyfish was going to be an adventure for both of us.  Turritopsis turned out to be pretty difficult to acquire, and while we waited for them to show up from Japan (the jellies eventually arrived but were not healthy and we couldn’t revive them) I thought it would be good practice to work with a more common jellyfish.  We contacted the nearby Cabrillo aquarium and got our hands on some moon jellies, Aurelia aurita, which is one of the most plentiful and widespread jellyfish in the world.  Once we had them growing in the lab, with the help of our talented lab tech Ty Basinger, I did some simple amputation experiments to broadly determine their regenerative ability.

The Regenerative Ability Of Jellyfish

Quickly I realized they were not regenerating the lost parts, and instead seemed to be reorganizing their existing parts while rebuilding essential body symmetry, work that we later published in PNAS in 2015.  The young jellyfish of Aurelia aurita, called ephyrae, rearrange their remaining arms in response to arm amputation, re-center their mouths, and rebuild their muscular networks.  This process is completed within 12 hours to 4 days, and we called it symmetrization. We found that forces generated by the muscular network, operating within the viscoelastic material that comprise jellyfish, drives the rebalancing of the arm positions, a process modeled by our collaborator Chin Lin, a mechanical engineer from Taiwan.  We also examined other jellyfish species and found that many underwent a similar reorganization process. This work demonstrated that reorganization to recover body symmetry is an agile strategy: it proceeds rapidly from various starting conditions using constitutive physiological machinery, and because new cells are not required, it is plausibly an energy conserving self-repair system.

We brought many jellyfish species into the lab as part of the symmetrization project, and one of them was Cassiopea, the upside-down jellyfish.  While working with them I noticed that they would pulse consistently except when I turned off the lights, at which point they would immediately freeze their activity for a few seconds.  I mentioned this behavior to two of my friends and colleagues, Ravi Nath, a worm sleep scientist in Paul Sternberg’s lab, and Claire Bedbrooke, an opsin engineer in Viviana Gradinaru’s lab, and we began quantifying their behavior in response to changing light conditions.  We developed a jellyfish tracking setup, and began recording their behavior over many days and nights, with the help of Justin Bois, a data analysis guru, and saw that they had a prolonged decrease in activity at night.

This led us to launch a full project to determine if Cassiopea were sleeping during the night, work we recently published in Current Biology.  We found that Cassiopea display the three key hallmarks of a sleep-like state.  First is a reversible quiescent state, basically a period of low activity distinguishable from a coma or hibernation by its reversibility.  Second is an increased arousal threshold, meaning that the animal requires a greater stimulus to induce arousal during quiescence.

Lastly is homeostatic regulation of quiescence, so if an animal is deprived of its nighttime quiescence it has a compensatory lower activity until it recovers.  We also determined that Cassiopea behavior is circadian regulated, they continue to cycle in activity even in the absence of light.  Finally, with the help of David Prober, a zebrafish sleep expert, we also found that Cassiopea displayed quiescence in response to melatonin, a deeply conserved sleep molecule, indicating a possible conservation of sleep mechanisms from jellyfish up through the phylogenetic tree.  This is the first study to show a sleep-like state in an organism without a brain as jellyfish have a diffuse nerve net rather than a centralized nervous system.

I’ve been lucky to be supported by my advisor, my department, and the greater Caltech community as I adventured into using jellyfish as a model for asking basic questions in biology, and I hope to continue this journey next year as a postdoc or an independent fellow.

This study, The Jellyfish Cassiopea Exhibits a Sleep-like State, was recently published in the journal Current Biology.