Theme 1: Core seasonal timer mechanisms

Theme 1: Core seasonal timer mechanisms

Time-keeping systems comprise input pathways for synchronization (entrainment) by environmental cues (zeitgebers = time givers) coupled to an endogenous core timer, which in turn governs phenotype through multiple output pathways. A remarkable feature is that core timers drive innate changes in physiology in the absence of external cues – e.g. the spontaneous loss and subsequent resumption of feeding behaviour in arctic charr overwintering under the ice, activation and termination of hibernation in ground squirrels buried in their hibernacula, and the formation of resting cysts (hypnozygotes) in marine unicellular organisms, which lie buried in sediment until reactivation. Dissecting the causal mechanisms underlying these innate calendars is a key theme of this research initiative.

We have been the leading contributors to work defining a region encompassing the hypothalamus and the pituitary gland as the strongest candidate for a localized seasonal pacemaker / calendar in mammals. Current hypotheses about the underlying timer mechanisms focus on histogenesis and epigenetic regulation in both tissues, and on rheostatic changes in thyroid hormone (TH) metabolic feedback mediated by enzymatic changes controlling TH metabolism.

We are currently investigating these ideas through funded projects in seasonal mammals (MSM mice, hamsters, sheep and birds, using approaches that combine endocrine and metabolic profiling of responses with analysis of upstream transcriptomic regulation. This leads to a picture that remains largely correlative in nature, and needs further refinement in order to establish satisfactory models for mechanistic causation. Methodology to achieve this aim will involve developing tools to test genetic causation in laboratory experiments (i.e. CRISPR-Cas9 and virally mediated transgenesis) and refined in-vivo sampling and delivery approaches so that key elements in metabolic and endocrine regulatory networks can be assayed, and pharmacologically manipulated.

Theme 2: Comparative seasonal chronobiology

Theme 2: Comparative seasonal chronobiology

The overarching hypothesis is that genetically encoded calendar timer mechanisms govern seasonal transitions, and that these will show adaptive divergence. To date, there have been no attempts to take an explicitly genetic approach to understand seasonal timing in animals, and we are presently addressing this through genome-wide approaches in animal breeding experiments, and through comparative genomics in ‘natural experiments’ provided by evolution of species over latitudinal clines. Both avenues necessitate a departure from ‘standard’ seasonal animal models.

In Atlantic salmon, we are undertaking a large-scale family-cross study to characterise genes underlying requirement for prolonged exposure to winter photoperiods on subsequent expression of the spring smolting phenotype. This is made possible through major aquaculture industry (MOWI) investment, our productive collaboration with salmon genomics specialists at NMBU / CigeneREF, and excellent research facilities at the Kårvika aquaculture field station in Tromsø.

We recently de novo assembled genomes for two species of vole, Microtus arvalis and M. oeconomus and are using these in whole genome resequencing and Fst analysis of variant populations from the northern and southern areas. This approach has successfully isolated a number of novel loci linked to seasonal adaptation, which we can follow-up in comparative laboratory experiments in the two species.

These comparative analyses are unbiased in their genetic focus, and provide a powerful complementary tool to the focussed approaches under Theme 1. Indeed these two themes are synergistic in terms of their capacity for knowledge generation. Continuing to refine and develop our genetics / genomics approaches is the second major priority of ASTI, and this will require further enhancement of data processing, data archiving and provisions for accessible data sharing.

Theme 3 – ‘One seasonal health’

Theme 3 – ‘One seasonal health’

The one health concept can be defined as "the collaborative efforts of multiple disciplines working locally, nationally, and globally, to attain optimal health for people, animals and our environment" (from the One Health Initiative Task Force, OHITF). This idea can be traced back to Hippocrates (c. 460 BCE – c. 370 BCE) in his text ‘On Airs, Waters, and Places’, which promoted the concept that public health depended on a healthy environment. In this context, seasonal influences on ‘one health’ are pervasive and of far-reaching importance, and anthropogenic impacts through climate change, and through habitat changes (e.g. light pollution, artificial rearing processes) are a major concern. We are currently developing the one seasonal health concept through the following avenues:

1. Seasonal regulation of immune function - We see seasonal modulation of immunity as core part of life-history trade-offs linked to bioenergetics, and this is supported by observations in mammals including humans: 23% of genes expressed in human PBMCs have coordinated seasonal expression. Our own data in ptarmigan and in salmon demonstrate clear seasonal changes in investment in immune competence, which are of major interest from an animal health perspective. We are developing this avenue in collaboration with the fish immunology and vaccinology (FIV) group, at UiT (West / Edholm /Jørgensen), following a strategy that will use state of the art approaches to immune cytology (e.g. single nuclei (sn)RNA seq, adoptive transfer experiments) in combination with detailed analysis of pathways linking light and time to endocrine function. This work has direct relevance to fish health during aquaculture production – for which losses during light-induced development are a major industry and welfare concern, and is also of basic relevance in terms of understanding how seasonal status impacts on immune function in vertebrates.
2. Human – animal interactions in arctic seasonal environments - Extreme seasonal variation in light exposure is the defining feature of the Arctic, and light pollution and mismatches between photoperiod and climatic cycles are modern challenges to human and ecosystem health. Given the fact that seasonal affectivedisorder (SAD) diagnosis increases with latitude it is particularly relevant in the Arctic to consider seasonal effects on humans. Our objective is to understand relationships between light and behavioural / physiological rhythms in humans and reindeer over daily and annual timescales, addressing three key questions: a) How are humans affected by year-round arctic lighting? b) How does the reindeer adapt to year round changes in natural lighting conditions? c) How does lifestyle affect behaviour & physiology in reindeer & humans in the real world? We have excellent, long-standing links with senior members of the local reindeer herding community who are interested in the scope for improving wellbeing through increased understanding of chronobiological aspects of human-animals interactions.
3. Plasticity for seasonal synchrony - Complementary to the idea of core genetically based timers is the concept of plasticity in time-keeping. This refers to the idea that the annual timing of phenotypic and phenological changes varies from year to year, even though photoperiod is an invariant annual zeitgeber. This implies that light synchronised timer systems do not determine the timing events in an absolute sense, but rather set windows in which events can happen. From a one seasonal health perspective this is important in at least two ways: first within a population / species, limited plasticity may compromise fitness (e.g. in unusually early or late spring years); secondly, such fitness effects may have indirect impacts on other populations species with which the directly compromised species interacts. This in essence is the widely discussed ‘seasonal mismatch’ problem.
   We see plasticity in timing as an epigenetic phenomenon in which the expression of outputs of the core timer, or possibly even the timer itself is modulated by environmental factors. We have established a ‘maternal photoperiodic programming’ paradigm in rodents (hamsters, MSM mice and voles) in which prenatal experience sets seasonal timer function through to adulthood, apparently at the level of the brain as outlined in Theme 1. We will continue this work by dissecting how this epigenetic influence is exerted at gene expression and brain metabolism levels, and extend the experimental paradigm to explore species variation in photoperiod x temperature and photoperiod x food interactions. This avenue will build on field biology / lab study synergies in voles and in reindeer.

Birth in the Arctic

ASTI are happy to announce the birth of 6 reindeer calves

We maintain a herd of Norwegian reindeer to research the physiological adaptations to the arctic in this species. We are thrilled to announce that we have 6 new additions to the herd and wish to share some pictures of our newborns enjoying their snowy outdoor enclosure.

ASTI on ice

ASTI members Lars Folkow, Chiara Ciccone and Shona Wood have recently returned from the east coast of Greenland, referred to the West ice (Vestisen) in Norway. The aim was to conduct multiple research projects in the ice but also run a research-led teaching cruise for UiT BIO-2310 students. ASTI aimed to contribute to the specific ASTI research project Clocks, hypoxia and metabolism.

Diving mammals have evolved several adaptations that enable them to cope with the limited availability of oxygen (hypoxia). Among pinnipeds, the hooded seal (Cystophora cristata) has remarkable diving capacities. A goal of ASTI is to develop methodologies to study hypoxia tolerance in a physiologically relevant model but while minimising the use of animals while maximising the quality of data.

The hooded seal is known for its remarkable diving capacities: dives as long as 1 hour and as deep as 1600 m have been recorded (Folkow and Blix, 1999; Andersen et al., 2013; Vacquie-Garcia et al., 2017). Because of these abilities, the hooded seal has been considered an ideal research model in both diving and hypoxia-tolerance physiology in a wide number of studies (Folkow et al., 2008; Mitz et al., 2009; Vázquez-Medina et al., 2011; Fabrizius et al., 2016; Geiseler, Larson and Folkow, 2016; Hoff et al., 2016, 2017; Geßner et al., 2020). However, access to these animals is limited, they are only accessible in the breeding season (March) located within the pack ice off Jan Mayen/east coast of Greenland, Davis Strait and the coast of Labrador.

PhD student Chiara Ciccone and MSc student Fayiri Kante have been developing techniques to grow cells from these animals with the hope of making 100’s of experiments possible from one animal. We are happy to report that our recent trip was very successful, and we have many cells happily dividing in dishes ready for experiments over the next year into hypoxia and the interactions with the circadian clock in a highly hypoxia tolerant mammal.

We would like to thank the Helmer Hanssen crew and Captain for a successful research trip and the BIO-2310 UiT students for a fun research-based teaching opportunity. Final thanks go to the two polar bears that made a guest appearance on the ice.

 Polar bears in Vestisen Foto: Shona Wood

References

Andersen, J. M. et al. (2013) ‘Investigating annual diving behaviour by hooded seals (cystophora cristata) within the northwest atlantic ocean’, PLoS ONE, 8(11). doi: 10.1371/journal.pone.0080438.

Fabrizius, A. et al. (2016) ‘When the brain goes diving: Transcriptome analysis reveals a reduced aerobic energy metabolism and increased stress proteins in the seal brain’, BMC Genomics, 17(1). doi: 10.1186/s12864-016-2892-y.

Folkow, L. P. et al. (2008) ‘Remarkable neuronal hypoxia tolerance in the deep-diving adult hooded seal (Cystophora cristata)’, Neuroscience Letters, 446(2–3), pp. 147–150. doi: 10.1016/j.neulet.2008.09.040.

Folkow, L. P. and Blix, A. S. (1999) ‘Diving behaviour of hooded seals (Cystophora cristata) in the Greenland and Norwegian seas’, Polar Biology, 22(1), pp. 61–74. doi: 10.1007/BF02329206.

Geiseler, S. J., Larson, J. and Folkow, L. P. (2016) ‘Synaptic transmission despite severe hypoxia in hippocampal slices of the deep-diving hooded seal’, Neuroscience, 334, pp. 39–46. doi: 10.1016/j.neuroscience.2016.07.034.

Geßner, C. et al. (2020) ‘Cell Culture Experiments Reveal that High S100B and Clusterin Levels may Convey Hypoxia-tolerance to the Hooded Seal (Cystophora cristata) Brain’, Neuroscience, 451(October), pp. 226–239. doi: 10.1016/j.neuroscience.2020.09.039.

Hoff, M. L. M. et al. (2016) ‘An atypical distribution of lactate dehydrogenase isoenzymes in the hooded seal (Cystophora cristata) brain may reflect a biochemical adaptation to diving’, Journal of Comparative Physiology B: Biochemical, Systemic, and Environmental Physiology, 186(3), pp. 373–386. doi: 10.1007/s00360-015-0956-y.

Hoff, M. L. M. et al. (2017) ‘Transcriptome analysis identifies key metabolic changes in the hooded seal (Cystophora cristata) brain in response to hypoxia and reoxygenation’, PLoS ONE, 12(1), pp. 1–21. doi: 10.1371/journal.pone.0169366.

Mitz, S. A. et al. (2009) ‘When the brain goes diving: glial oxidative metabolism may confer hypoxia tolerance to the seal brain’, Neuroscience, 163(2), pp. 552–560. doi: 10.1016/j.neuroscience.2009.06.058.

Vacquie-Garcia, J. et al. (2017) ‘Hooded seal Cystophora cristata foraging areas in the Northeast Atlantic Ocean—Investigated using three complementary methods’, PLOS ONE. Edited by Y. Ropert-Coudert, 12(12), p. e0187889. doi: 10.1371/journal.pone.0187889.

Vázquez-Medina, J. P. et al. (2011) ‘Maturation increases superoxide radical production without increasing oxidative damage in the skeletal muscle of hooded seals (Cystophora cristata)’, Canadian Journal of Zoology, 89(3), pp. 206–212. doi: 10.1139/Z10-107.

Our Svalbard ptarmigan get a new home

This Monday (04.04.2022), we proudly transferred our first Svalbard ptarmigans into the newly finished aviary.

 Now, our birds have not only more space to pursue their ptarmigan ambitions but are also matched with their partners for the upcoming breeding season. Talking of love birds. While some were stunned by their new surroundings, others wasted no time to vocalise their arrival and showing the new furniture who is boss.

We are all looking forward to the new and exciting research possibilities.   

ASTI RESEARCHERS MAKE MAJOR (RE-)DISCOVERY

In an exciting development today, senior members of the ASTI research group in Tromsø re-discovered the Sun. This resolves a perplexing puzzle that has been dogging Arctic researchers since mid-November: Why isn´t it getting light anymore?

 

Over a period of weeks, painstaking research appeared to be leading nowhere, with attempts to find our favourite celestial body becoming ever more desperate. Indeed Prof Jørgen Berge, Dean of Biosciences (and some other stuff) in Tromsø, who was definitely not involved in this study, hypothesised that the most likely explanation was that the Sun had disappeared beneath the sea – explaining the maintained circadian entrainment of plankton even in December.

Rejecting this hypothesis, ASTI researchers Wood and Hazlerigg bravely set out on mission to find the Sun, armed only with a large thermos of sweet tea. To their surprise, slightly before midday today, they spotted their quarry in a southerly direction, just above the horizon. In a further development they also found their shadows, refuting earlier suspicions that they had become vampires.

“Imagine our amazement, it was big and orange and made us feel happy” said Dr Wood, who led the study.

“Re-discovering the Sun, is perhaps the most important thing for life in the Arctic” said Professor Hazlerigg, who has been unusually grumpy these last two months.

“If they had only bothered to consult the published literature, they would have realised that this happens every year”, said Professor Arnoldus Blix, who was very definitely not involved in the study, but knows more than most about the old literature.

Nevertheless, this is a great discovery for the residents of Tromsø with wide-reaching significance for mental health, vitamin D deficiency, obesity, chrono-disruption and world peace.

ASTI extends its condolences to the residents of Svalbard who are yet to re-discover the sun.  Plans to send Professor Hazlerigg to the high Arctic archipelago to help with efforts to find the sun are in process with the Governor of Svalbard.

Happy Soldagen from ASTI

Independent research fellow position available

A 4 year independent research fellow position available within ASTI - with further prospects for permanent appointment.

The appointee will be expected to develop their own main line of research to complement and augment parallel research programmes within ASTI, and to align with one or more of the overarching thematic headings: Core seasonal timer mechanisms and outputs; Comparative seasonal chronobiology; One seasonal health.

The appointee will become an integral member of the Arctic Chronobiology and Physiology research group, which is based on the UiT Brevika campus and leads the ASTI programme. This is a young and growing research grouping with a strong collective ethos of interdisciplinarity and collaboration, which will offer excellent opportunities to co-develop collaborative projects under the ASTI umbrella. 

Membership of this group will provide excellent further training and career development opportunities, in both research and pedagogical aspects, enabling the appointee to compete for future long-term career positions.

For further information regarding this position, please contact Professor David G. Hazlerigg, david.hazlerigg@uit.no phone +47 77 64 48 71 and look at the full description of the position here:

https://www.jobbnorge.no/en/available-jobs/job/208025/researcher-within-the-arctic-seasonal-timekeeping-initiative

More coverage for our ptarmigan!

Ptarmigan research goes mainstream

Do Svalbard ptarmigan need a circadian clock in a rather arrhythmic environment such as the High Arctic? During the polar day and polar night, which makes up 2/3 of their seasonal life, they are active around the clock. This suggests a lack of circadian control over behaviour. However, in a recent study from our ACP-research group we showed that the circadian clock is still an integral part of seasonal timekeeping.

While circadian based seasonal timing is widely accepted in the field of chronobiology, our study is the first to show that the same mechanism operates in permanent residents of the High Arctic.

Hence, Svalbard ptarmigan display a chronobiological adaptation perfectly suiting their habitat. They can ignore their circadian clock in terms of behaviour but are still able to utilize it in order to time seasonal events such as reproduction.

The study is published in Current Biology and is featured in Nature News.

The high impact of the article clearly shows that the world craves more research on Svalbard ptarmigan. Luckily, the ACP-research group combined with the newly founded Arctic Seasonal Timekeeping Initiative (ASTI) is ready to provide.

NEW HIBERNATION FACILITY ESTABLISHED AT UIT!

We are happy to announce that the new Hibernation research facility is now operational at UiT. The Tromsø forskningsstiftelse (TFS ) award to Dr. Shona Wood and the UiT supported  Arctic Seasonal Timekeeping Initiative (ASTI) have made it possible to establish the first hibernation research facility in Norway.

Hibernation is a physiological and behavioural adaptation that permits survival during periods of reduced food availability and extreme environmental temperatures in several mammalian species. This is achieved through cycles of metabolic depression and reduced body temperature (torpor) and rewarming (arousal).

From an human perspective, the ability of hibernating animals to arouse to a normal body temperature state after extended periods of cooling to temperatures as low as 0 degrees is nothing short of miraculous. We aim to focus on the role of the brain in this process, and the issue of how it maintains the ability to control temperature within safe limits during torpor, and then subsequently drives and co-ordinates rewarming of the organism. This undertaking addresses a basic biological mystery with great applied importance: how hibernators allow their brains to cool and become hypoxic and are then able to re-warm them returning to a healthy euthermic state, this is of clear biomedical relevance in terms of tissue/organ cryopreservation and transplantation, surgery and recovery from hypothermia.

Deep thanks and acknowledment go to PhD students Vebjørn Melum and Fredrik Markussen in making this possible. More information on the facility and project aims can be found on the ASTI website: https://uit.no/research/asti/project?pid=717950

 Photo credit: Fredrik Markussen

Two PhD thesis defended in the same week!

An exciting week for the members of ASTI with two PhD thesis successfully defended.

Congratulations to Dr. Daniel Appenroth who successfully defended his PhD thesis entitled "Circadian-based processes in the high Arctic: activity, thermoregulation and photoperiodism in the Svalbard ptarmigan (Lagopus muta hyperborea)" on the 15th April 2021.

You can read Daniel's thesis and the three published papers here. Daniel was supervised by the ASTI centre director Prof. David Hazlerigg and ASTI researcher Dr. Alex West, along with Dr. Gabi Wagner. The evaluation committee consisted of Professor Brian Follett (1. opponent) and Dr. Gisela Helfer (2. opponent), with ASTI's Professor Lars Folkow as the internal member and leader of the committee.

 

 

Congratulations to Dr. Marianne Iversen who successfully defended her PhD thesis entitled "Photoperiodic history-dependent preadaptation of the smolting gill" on the 16th April.

You can read Marianne's thesis and three published papers here. Marianne was supervised by Prof. David Hazlerigg and Prof. Even Jørgensen. The evaluation committee consisted of Associate Professor Steffen Madsen, University of Southern Denmark, Denmark (1. opponent) and Professor Jon Vidar Helvik, University of Bergen (2. opponent), with Dr. Eva-Stina Edholm, an ASTI collaborator in the Norwegian College of Fishery Science as internal member and leader of the committee).

 

An excellent two days of science representing all the hard work relating to seasonal timing we do here at ASTI. Hopefully many more successful defences and papers to come!

ARCTIC SEASONAL TIMEKEEPING INITIATIVE LOGO COMPETITION!

23 million kroner awarded to ASTI!

David Grey Hazlerigg  –  Professor

Shona Wood  –  Associate Professor

Alexander Christopher West  –  Researcher

Lars Folkow  –  Professor

Even Jørgensen  –  Professor

Daniel Appenroth  –  Postdoctoral Fellow

Vebjørn Jacobsen Melum  –  PhD fellow at Arctic Chronobiology and Physiology

Chiara Ciccone  –  Doctoral Research Fellow

Fredrik Andreas Fasth Markussen  –  Doctoral Research Fellow

Jana Kalinova  –  Doctoral Research Fellow

Roelof Hut  –  Professor

Kelly Drew  –  Professor

Stafford Lightman  –  Professor