Sleep, Circadian Rhythms, and Cognition: Bridging the Genotype-Phenotype Gap

29 – 30 November 2007

Workshop Report

The target audience of the workshop was scientists with an interest in integrating the disciplines of molecular biology, physiology, and psychology towards a widened understanding of sleep, circadian rhythms, and cognition. The workshop aimed to exploit our knowledge about genome sequences and genomic variation and how to best relate this to individual differences in sleep physiology and cognition. The organisers were aiming for vivid discussions toward an integrated consensus on the current status of the field, and the most fruitful areas for future developments.

The workshop was held on 29 and 30 November 2007 at the Postgraduate Medical School of the University of Surrey. Attendees came from Belgium (1), France (1), Japan (2), Switzerland (4), the United States (3), and the UK (25). An opening reception was held at the Holiday Inn, where the external visitors were staying, on the evening of 28 November.

The theme for the first session was "Circadian rhythms: From molecules to rhythmicity", chaired by Malcolm von Schantz. The session was opened with a talk by Toru Takumi (Osaka), whose presentation described a systems biology approach to studying the molecular mechanism of the biological clock and its outputs. The second talk, by François Royer (Paris) descried how the circadian clock in turn controls behaviour, using Drosophila as a model system.

The second session, chaired by Derk-Jan Dijk, was entitled "Sleep: From genes to EEG and development". The first talk, by Paul Franken (Lausanne), challenged the nomenclature of clock genes, sleep genes, and metabolic genes, presenting arguments for a considerable degree of pleiotropy. Marcos Frank (Philadelphia) described work on sleep and cortical plasticity in the developing brain, after which Christian Cajochen (Zürich) closed the session with a presentation on EEG correlates of circadian rhythms, performance, and memory.

Annette Sterr chaired the following session, "Cognition: Individual differences and models". Annette Karmiloff-Smith (London) provided a refreshing insight from developmental psychology by describing sleep-related brain activity and consolidation of learning in children with genetic developmental disorders. This was followed by a presentation by Hans van Dongen (Spokane), who described the different contributions of homeostatic and circadian factors, and interindividual variability, in cognitive performance impairment.

The last session of the first day was entitled "Interactions between sleep and circadian rhythms in normal and disordered sleep", and was chaired by Simon Archer. In the first presentation, Derk-Jan Dijk (Guildford) argued that established models for individual differences in sleep homeostasis and circadian rhythmicity may be explained by differences in specific genes. Covering disordered sleep, Hirokuni Tagaya (Kodaira) suggested that delayed sleep phase disorder is a disorder of entrainment rather than of rhythm parameters.

Each session had half an hour scheduled for discussion between the participants, which was lively and also allowed the participation of participants who were not presenting. The first day ended with a conference dinner in Clandon.

The second day begun with the theme "Interactions between sleep, rhythms, and cognition: Humans and animals", chaired by John Groeger. The first speaker, Jim Horne (Loughborough), introduced by the chair as the doyen of British sleep research, covered human aspects of the theme with some interesting studies from his group. Animal studies were discussed by Chris Colwell (Los Angeles), who described experiments on circadian control of learning and memory in the mouse.

The penultimate session, "Closing the gaps: From genes to physiology", was chaired by Colin Smith. Mehdi Tafti's (Lausanne) talk described their recent identification of Homer-1a as a molecular correlate of sleep loss in the mouse brain. The link from genes to physiology was further explored by Michael Hastings (Cambridge), who talked about the dynamics of the clock gene machinery in the brain and in the peripheral clocks.

The workshop was closed with the session "Closing the gaps: Physiology, imaging, and cognition", chaired by John Groeger. This was opened by Simon Archer (Surrey), who used data from subjects carrying two different variants of the PER3 gene to show the path from an association study to a prospective study, and the insights that this has yielded into aspects of the phenotype ranging from molecules to behaviour. Hans-Peter Landolt (Zürich) spoke on the role of genotype in the relationship between sleep vs vigilance and stimulants. The final talk was a tour de force by Pierre Maquet (Liége), whose work on functional imaging provided a perfect final example of how the gaps between physiology and cognition and between genotype and phenotype can be bridged.

Feedback from attendees was 100% positive. Participants expressed their appreciation of the high quality of the presentations and the wide range of world experts that had been assembled. The meeting also served as a conduit for attendees to work on joint publications and to discuss future grant applications. A flyer in the conference package about the University of Surrey's PTY placement scheme was successful in identifying potential new international placements that are currently being pursued and appear likely to be realised for the next academic year.

The organising committee consisted of Malcolm von Schantz (Chair), Derk-Jan Dijk, Simon Archer, John Groeger, and Antoine Viola. The committee is indebted to Wendy May and Sarah Wane for assistance with practical arrangements, to Jo Jones for providing the coffee and tea breaks, to Lawrence Wakile and Alan Brown for the arrangements with the PGMS building, and to Young's Kitchen for the popular catering. Last, but not least, we acknowledge the sponsorship of the Institute of Advanced Studies, the Surrey Sleep Research Centre, Philips, and Novartis.

Contact: m.von.schantz@surrey.ac.uk

2 March, 2008