DG-MC-MCC · Modelling the molecular regulatory bases of circadian clocks

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Project objective

This project aims to understand the design principles underlying the biochemical mechanisms of circadian clocks, by combining my training in mathematical analysis with the host laboratory's expertise in experimental circadian biology. The circadian clock controls 24-hour rhythms in processes from metabolism to behaviour, including the rhythmic expression of 5-10% of all genes in higher eukaryotes. The pervasive control by the clock profoundly affects human physiology and plant growth, and hence affects health, industry and agriculture. Recent advances in molecular biology of mammals, insects, plants and fungi show that only a few genes form the core regulatory loops of the clock mechanism. These genes have been manipulated in subtle genetic studies, including in the host laboratory. The limited complexity and the rich experimental data make the clock system particularly well suited for mathematical modelling.We are particularly interested to understand how variation in external time cues (i.e. light and temperature) is integrated with internal, biological signals, in order to maintain biological rhythms at an optimum phase relative to the day/night cycle, but also to the mechanism by which the output pathways control rhythmic gene expression at all possible phases. To address these issues, we will apply theoretical and computational approaches, whose goal is to reveal the role of the regulatory feedback loops involved in the network of clock genes in all species. This should allow us to explain the molecular origin of the characteristic features of circadian rhythms, including light and temperature sensitivity. Furthermore, the question of robustness of circadian oscillations to parameters and to molecular noise will also be addressed. The principles revealed by studies of the clock network will very likely apply to other gene networks, particularly the oscillatory circuits that control cell division (and thus cancer) and embryonic segmentation.

Original text from CORDIS.

Participants

• UNIVERSITY OF WARWICK · COVENTRYCoordinatorUnited Kingdom

Links

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