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The main interest of my lab is to investigate how solar and lunar light are sensed by the nervous system and how this light information impacts on the animals' information processing and endogenous clocks.
The moon is an important timing cue for numerous marine species, ranging from corals to worms, fishes and turtles. Such lunar timing controls reproductive development, physiology and behavior. Despite the fundamental nature and widespread occurrence of lunar-controlled rhythms, little is known about their molecular mechanisms, their interplay with rhythms and oscillators of different period lengths, and their modulation in changing environments. We focus on the marine bristle worm Platynereis dumerilii and the midge Clunio marinus to close these knowledge gaps. Techniques, including transgenesis, inducible cell ablations, as well as TALEN/Crispr-Cas-mediated genome engineering provide us with first insights into the genes required for solar vs. lunar light detection. Linked to our interest in photoreceptors, we uncovered the presence of functional opsin photoreceptors in inter- and motorneurons of medaka and zebrafish. We propose that they might function as nature’s own optogenetics.
Kristin Tessmar studied biology at the University of Heidelberg, with research at the MGH, Boston, the EMBL-Heidelberg and the University of Cambridge, UK. After her doctorate from the University of Marburg, she did her post-doc at the EMBL, Heidelberg. In 2008 she joined the Max Perutz Labs/ University of Vienna as a junior group leader. Since 2017 she is full professor for chronobiology.
(2016) NATURE. PMID: 27871090
What marine midges can tell us about clocks and calendars
The non-biting marine midge Clunio marinus lives along Europe’s tide-shapen coasts, where precise timing is of existential importance: Reproduction and oviposition must occur when the tide is at its lowest.
The tides, and therefore also low tide, are influenced by both the sun and the moon. To foresee the ideal time of reproduction, Clunio has two internal clocks: a circadian (daily) clock, comparable to a watch, set by the sun, and a circalunar (monthly) clock, comparable to a calendar, set by the moon.
Due to geographical causes, the timing of low tides differs between geographical locations. Therefore, the midges have to “set” their clocks in accordance with their position. Scientists had already discovered in the 1960s that midges living along the coast of the Atlantic sea have genetically adapted their circadian clocks to the local occurrence of tides.
Kristin Tessmar-Raible and her team then investigated how such adaptations may occur on a molecular level. The work was spear-headed by the post-doc Tobias Kaiser, who had previously already uncovered that similar adaptations are also true for circalunar clocks.
Tobias sequenced and compared different Clunio genomes in a tight collaboration with Arndt von Haeseler’s group. This allowed the researchers to unravel the genomic sequences that likely underlie the circadian and circalunar timing differences. Further molecular work involving VBC PhD student Birgit Poehn and collaborations with Thomas Hummel’s (Faculty of Life Sciences, University of Vienna) and Florian Heyd’s groups (FU Berlin, Germany) then provided a first mechanistic model, how such molecular adaptations can lead to differential circadian timing.
The researcher’s results point towards a specific protein, called Calcium/Calmodlin-dependent kinase II (CaMKII), being the main effector behind the adaptation of the circadian clock to the geographical environment. “Different variants of CaMKII appear to let the circadian clock run either faster or slower,” explains Tessmar-Raible. “And it is of course an interesting aspect that this protein, which hasn’t changed much during the course of evolution, can also be found in humans. The question therefore emerges, if CaMKII can also play a role in human chronotypes.”
Remarkably, the protein CAMKII is one of the most abundant proteins in the human brain and has already been linked to neuropsychiatric disorders, which often appear in conjunction with malfunctions of the circadian clock. “Our study raises many intriguing questions – apart from the modulation of the circadian clock, it also suggests molecular candidates for the modulation of the ‘internal calendar’, the lunar clock. And in understanding these clocks we are still at the very beginning,” comments Tobias Kaiser.
(2017) Nature Methods. PMID: 28825703
When fish swim in the holodeck: Virtual worlds allow new experimental designs for the study of brain function
A person sees another person and depending on the context very different interactions can take place. The final outcome after the initial visual experience is a result of complex interactions of neurons in different brain regions- processes that are still very little understood. To study the neuronal basis underlying behavior, scientists have developed a broad range of techniques, most of which require either the partial or full immobilization of the animal. This restricts sensory input and feedback and ultimately changes the neuronal and behavioral responses. In addition, mimicking natural conditions in a laboratory is difficult.
The groups of Andrew Straw at the University of Freiburg, Germany and Kristin Tessmar-Raible developed a system called “FreemoVR”, that overcomes most of these hurdles by immersing a freely-moving animal in a reactive, three-dimensional world controlled by a computer. FreemoVR enables the experimenter to control the animal’s visual experience, while maintaining the natural feedback for its tactile senses.
To do so, the scientists built behavioral arenas whose walls or floors were computer displays, including arbitrarily shaped projection surfaces. Using computer games technology, the animal could then explore the VR environment in these arenas from its own perspective while it walked, flew or swam.
“We wanted to create a holodeck for animals so that they would experience a reactive, immersive environment under computer control so that we could perform experiments that would reveal how they see objects, the environment, and other animals,” says Andrew Straw, leading in the development of FreemoVR.
Using FreemoVR, the teams found previously unnoticed behavioral differences between a wildtype and a mutant zebrafish strain, showing the sensitivity of the system. The scientists further explored the rules that govern social interactions of real zebrafish with virtual ones and found that the prospective leader fish minimizes the risk of losing followers by balancing his internal preference for a swimming direction with the social responsiveness of the subordinate fish.
(2013) Cell Rep;5:1-15. PMID: 24075994
The endogenous calendar of marine animals
The bristle worm Platynereis dumerilii possess a monthly (circalunar) clock that runs independently of the oscillations of its daily (circadian) clock. However, both clocks jointly regulate the level of specific transcripts, as well as locomotor behavior.
As humans, we are used to measure time periods of different lengths. We look at our watches to be in time for activities during the solar day, but we also use calendars to time activities on the time scale of lunar months, or celebrate holidays according to specific seasonal events, e.g. equinoxes and longest/ shortest days.
Obviously, animals neither possess watches nor calendars. However, they do exhibit physiological or behavioral rhythms on very different time scales. If such rhythms continue even in the absence of external stimuli, it means that endogenous oscillators, so-called molecular clocks, control them.
In addition to the daily cycles provided by the sun, many marine animals – ranging from corals to vertebrates – utilize the steady cycle of the moon to synchronize reproductive behaviour and sexual maturation on a monthly schedule. It has been shown that several of these species indeed possess an endogenous monthly oscillator (called a circalunar clock) in addition to their circadian clocks. The molecular mechanisms of such non-circadian clocks, however, have remained obscure. Even the seemingly simple question if the circalunar clock requires the circadian clock for its function had remained open. In collaboration with the group of Tomoko Ishikawa (Osaka University; one of our HFSP team partners) and Andrew Straw from the Institute for Molecular Pathology (IMP), we laid first molecular groundwork to understand the circalunar clock of the bristle worm Platynereis dumerilii. Most interestingly, by blocking the function of casein kinase1∂/ε, a key regulator of animal circadian clocks, we found that the circalunar clock is independent of the oscillations of the worm’s circadian clock. This strongly suggests that circadian and circalunar clocks are molecularly distinct. In turn, however, we also found that the circalunar clock impacts on the worm’s circadian locomotor behavior: Whereas during “new moon” days, worms were mostly active during the night, they showed much shorter activity cycles and more activity during the day when analyzed two weeks later when they expected to be in a “full moon” period. Notably, the worms exhibited this behavioral change, even if the dim nocturnal light stimulus that signals ‘full moon’ to them was omitted in these experiments, providing strong evidence that the change is indeed controlled by their internal circalunar oscillator, and not simply a response to nocturnal light.
Circadian and circalunar clock interactions in a marine annelid
Zantke, J; Ishikawa, T; Arboleda, E; Lohs, C; Schipany, K; Hallay, N; Straw, A; Todo, T, Tessmar-Raible, K
The genomic basis of circadian and circalunar timing adaptations in a midge.
Kaiser, Tobias S; Poehn, Birgit; Szkiba, David; Preussner, Marco; Sedlazeck, Fritz J; Zrim, Alexander; Neumann, Tobias; Nguyen, Lam-Tung; Betancourt, Andrea J; Hummel, Thomas; Vogel, Heiko; Dorner, Silke; Heyd, Florian; von Haeseler, Arndt; Tessmar-Raible, Kristin
Virtual reality for freely moving animals.
Stowers, John R; Hofbauer, Maximilian; Bastien, Renaud; Griessner, Johannes; Higgins, Peter; Farooqui, Sarfarazhussain; Fischer, Ruth M; Nowikovsky, Karin; Haubensak, Wulf; Couzin, Iain D; Tessmar-Raible, Kristin; Straw, Andrew D
Project title “Dissecting the mechanistic basis of moon-controlled monthly timing mechanisms in marine environments”
Project title “Analyses of inner brain Opsins in the vertebrate CNS”
Project title: “Molecular neurobiology of a moonlight entrained circalunar clock”