ASTI | UiT

Research themes

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.

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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.

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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:

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.
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.
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.

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People

David HazleriggProfessor (Group leader)

Shona WoodAssociate Professor

Shona Wood – Associate Professor

Research interests:

Accurate timing and anticipation of seasonal changes is required to initiate physiological adaptations over the course of the year such as hibernation, changes in metabolism, fattening and reproductive activity. To achieve this, organisms have evolved complex seasonal timekeeping systems that rely on day length sensing (photoperiodism), coupled to innate long-term timers ("circannual clock"). The fundamental biological processes giving rise circannual rhythms are not known for any organism. This is a highly integrative topic of wide relevance, integrating multiple levels of understanding from genome to ecosystem. Within this area, my specific interests are:

The cellular and molecular mechanisms involved in seasonal timekeeping processes
The adjustment of homeostatic set points in physiology (rheostasis)
The function of a specialised cell type in the hypothalamus, the tanycyte, in the above processes
The use of hibernation and maternal photoperiodic programming to investigate the above processes

Current projects:

Arctic seasonal timekeeping initiative (ASTI), role: Deputy director

ASTI is a capacity-building project to establish UiT as a centre of excellence for research into seasonal timekeeping mechanisms. This fills a strategic gap in chronobiology research worldwide, and is an excellent fit to UiT as the world’s northernmost research university. See the website for themes and specific research projects: https://uit.no/research/asti

Tromsø Forskningsstiftelse (TFS) starter grant: Epigenetic light, role: project leader

Website. The project aim was establish my lab in seasonal timekeeping and hibernation at the university of Tromsø. Specific areas of research were the epigenetic basis of seasonal timing, the role of circadian clocks in seasonal timekeeping, and maternal photoperiodic programming effects.

Sentinel North Transdisciplinary Research Program Université
Laval and UiT, The role of circadian clocks in seasonal synchrony in the Arctic, role: Co-PI

This is a comparative circadian/seasonal clockwork project with an emphasis on birds, fish and diatoms.

Clocks and hypoxia: Linking oxygen to time, role: Co-PI

This is a project investigating the role of circadian clocks and hypoxia in a
diving mammal (hooded seal) . It uses high-resolution respirometry of mitochondria, astrocyte/neuronal culture techniques, and lentiviral
reporters to unpick responses to hypoxia in a highly hypoxia-tolerant
animal.

Contact:

Position: Associate Professor

E-mail: shona.wood@uit.no

Work phone: +4777644784

Link to employee page (Shona Wood)

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Lars FolkowProfessor

Barbara Mizumo TomotaniResearcher

Barbara Mizumo Tomotani – Researcher

Research interests:

I am interested in the evolution of clocks and calendars in wild organisms and how the timing of daily and seasonal events is affected by global environmental change. My research strategy involves a combination of field and laboratory experiments and analyses of long-term datasets, mostly using songbirds.

Wild clocks:
Most organisms organize their activities through circadian (i.e. day/night) clocks, which in turn are entrained to environmental information such as light. Circadian clocks allow organisms to anticipate daily events and are ubiquitous in nature. They “tick” at different rates in different individuals, thus showing variation in their properties, such as period length, which is highly heritable. But the evolution of clocks is only possible if this variation is also associated with fitness differences. Currently, however, the selection of clocks under natural conditions remain poorly understood, for this, we need to study ‘wild clocks’ and connect the clock properties measured in the lab with fitness measures in the wild.

Urban clocks:
The light/dark cycle is the most important synchronizer of the biological clocks. Cities remarkably change the environment and one of the obvious impacts is the amount of artificial light at night present in the urban environment. I study the process of urbanization as a natural experiment to test the prediction that by dramatically changing the environment, cities expose organisms to profoundly distinct selective pressures compared to their natural environment and select different clock properties. Using the great tit (Parus major) as a model species, I measure the clock of individuals in cities and forests and carry out a large-scale common-garden study to separate genetic and environmental effects. I am particularly interested in possible differences in the clock's sensitivity to light.

Latitudinal clocks:
Following up on the urban clock project, I am interested in exploring the latitudinal adaptation of circadian clocks. When they move to the arctic, organisms are exposed to more extreme conditions of light, what would be the effects of artificial light at night on the clock in such environments? I am also using the great tits in this project and I hope to expand the common garden protocol to include birds from distinct latitudes.

Calendars in a changing world:
Animals need to time their daily and seasonal activities so they match favourable conditions in the environment. To do so, they use predictive environmental cues, with the photoperiodic and temperature variation being the most important ones for seasonal rhythms. Climate change is a major challenge that organisms face because by disrupting those important cues, they interfere with the animals' abilities to make predictions and may impact survival and reproductive success. I studied the effects of climate change on the timing of annual-cycle stages of a migratory bird: the pied flycatcher (Ficedula hypoleuca). Long-distance migrants, such as flycatchers, have complex annual cycles comprising several events, like breeding and migration, that need to be fitted into one year. Climate change advances annual-cycle stages, but, because not all stages respond to changes in temperatures, the shifts may vary depending on the stage (e.g. reproduction advances faster than migration). This could lead to a mismatch across the entire annual cycle because it modifies the time available for each stage.

External collaborators: Marcel E. Visser, Kees van Oers (NIOO, Netherlands Institute of Ecology)

Contact:

Position: Researcher

E-mail: barbara.m.tomotani@uit.no

Work phone: +4777644490

Link to employee page (Barbara Mizumo Tomotani)

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Alex WestResearcher

Daniel AppenrothPostdoctoral Fellow

Daniel Appenroth – Postdoctoral Fellow

Research interests:

Publications

Evidence for circadian-based photoperiodic timekeeping in Svalbard ptarmigan, the northernmost resident bird. Daniel Appenroth, Gabriela C. Wagner, David G. Hazlerigg, and Alexander C. West. Current Biology (2021). DOI: 10.1016/j.cub.2021.04.009
Body temperature and activity rhythms under different photoperiods in high Arctic Svalbard ptarmigan (Lagopus muta hyperborea). Daniel Appenroth, Andreas Nord, David Gray Hazlerigg, and Gabriela Christina Wagner. Frontiers in physiology 12 (2021): 256. DOI: 10.3389/fphys.2021.633866
Photoperiodic induction without light-mediated circadian entrainment in a high arctic resident bird. Daniel Appenroth, Vebjørn J. Melum, Alexander C. West, Hugues Dardente, David G. Hazlerigg, and Gabriela C. Wagner. Journal of Experimental Biology 223, no. 16 (2020). DOI: 10.1242/jeb.220699
Mechanisms of temperature modulation in mammalian seasonal timing. Laura van Rosmalen, Jayme van Dalum, Daniel Appenroth, Renzo TM Roodenrijs, Lauren de Wit, David G. Hazlerigg, and Roelof A. Hut. The FASEB Journal 35, no. 5 (2021): e21605. DOI: 10.1096/fj.202100162R

Other academic works

Circadian-based processes in the High Arctic: activity, thermoregulation and photoperiodism in the Svalbard ptarmigan (Lagopus muta hyperborea). Daniel Appenroth. Dissertation, UiT Norges arktiske universitet (Norway), 2021. DOI: 10037/20675
Core body temperature cycles in captive Svalbard rock ptarmigan (Lagopus muta hyperborea). Daniel Appenroth. Master's thesis, UiT Norges arktiske universitet (Norway), 2016. DOI: 10037/10005
Analysis of functional and morphological changes in the anterior cingulate cortex of Sharp-1 and Sharp-2 double knockout mice. Daniel Appenroth. Bachelor’s thesis, University of Göttingen (Germany), 2013.

Contact:

Position: Postdoctoral Fellow

E-mail: daniel.appenroth@uit.no

Work phone: +4777644805

Private phone: 98626116

Link to employee page (Daniel Appenroth)

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Fernando Cazarez MarquezPostdoctoral Fellow

Mattis Jayme van DalumResearcher

Vebjørn Jacobsen MelumDoctoral Research Fellow

Chiara CicconeDoctoral Research Fellow

Fredrik Andreas Fasth MarkussenDoctoral Research Fellow

Jana KalinovaDoctoral Research Fellow

Anna HofingerDoctoral Research Fellow

Arctic Seasonal Timekeeping Initiative - a UiT Aurora Centre

About

Research themes

Specific research projects

People

About

Research themes

Theme 1: Core seasonal timer mechanisms

Theme 2: Comparative seasonal chronobiology

Theme 3 – ‘One seasonal health’

Specific research projects

People

David Hazlerigg – Professor

Shona Wood – Associate Professor

Lars Folkow – Professor

Barbara Mizumo Tomotani – Researcher

Alex West – Researcher

Daniel Appenroth – Postdoctoral Fellow

Fernando Cazarez Marquez – Postdoctoral Fellow

Mattis Jayme van Dalum – Researcher

Vebjørn Jacobsen Melum – Doctoral Research Fellow

Chiara Ciccone – Doctoral Research Fellow

Fredrik Andreas Fasth Markussen – Doctoral Research Fellow

Jana Kalinova – Doctoral Research Fellow

Anna Hofinger – Doctoral Research Fellow