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.

ARCTIC SEASONAL TIMEKEEPING INITIATIVE LOGO COMPETITION!

23 million kroner awarded to ASTI!

David Hazlerigg  –  Professor

Shona Wood  –  Researcher

Lars Folkow  –  Professor

Even Jørgensen  –  Professor

Alexander Christopher West  –  Researcher

Anja Striberny  –  Postdoctoral Fellow

Vebjørn Jacobsen Melum  –  Doctoral Research Fellow

Chiara Ciccone  –  Doctoral Research Fellow

Fredrik Andreas Fasth Markussen  –  Doctoral Research Fellow

Kelly Drew  –  Professor

Stafford Lightman  –  Professor

Roelof Hut  –  Professor