Clock-cell specific physiological timing

Lead Research Organisation: University of Manchester
Department Name: School of Medical Sciences


Almost every bodily function is influenced by a biological clock within the brain, the suprachiasmatic nucleus (SCN), which serves to optimise internal physiology in anticipation of expected demands across the 24h day. Since the timing of peak demand varies between different behavioural or physiological processes (e.g. sleep, cardiovascular and gastrointestinal), particular aspects of physiology need to be individually timed to ensure health and well-being. The importance of this coordination is now well established: long-term disruptions to the clock are associated with serious adverse effects on health including increased risk of developing cancer or metabolic disease. Unfortunately, however, the mechanism by which the SCN achieves this precise coordination remains unclear.

Recent data suggest that optimal physiological alignment relies on the activities of specific subsets of clock cells with unique properties (e.g. their response to light1,2) that specialise them to regulate particular aspects of physiology. Under the guidance of a collaborative team, at the forefront of recent advances in the field1-4, here the applicant will test this hypothesis using the latest generation of viral/genetic targeting technologies, cutting edge multicellular recording approaches and comprehensive physiological and behavioural monitoring. Together these approaches will reveal how the activity of specific groups of cells within the SCN is used to regulate particular aspects of physiology or behaviour. Ultimately then, we anticipate that the information learned throughout the course of this project could help develop new ways of using light to manipulate internal timing that could be widely applicable in the real-world.

This project, suitable for motivated applicants with a degree in any appropriate branch of life sciences, thus represents a fantastic opportunity to develop a highly sought-after set of scientific skills and to contribute to a major advance in our understanding of how the brain controls daily variations in physiology.

1Walmsley L, Hanna L, Mouland J, Martial F, West A, Smedley AR, Bechtold DA, Webb AR, Lucas RJ, Brown TM. (2015) Colour as a signal for entraining the mammalian circadian clock. PLoS BioL 3:e1002127.

2Brown TM, Wynne J, Piggins HD, Lucas RJ. (2011). Multiple hypothalamic cell populations encoding distinct visual information. J Physiol. 589: 1173-1194.

3Pilorz V, Cunningham PS, Jackson A, West AC, Wager TT, Loudon AS, Bechtold DA. (2014). A novel mechanism controlling resetting speed of the circadian clock to environmental stimuli. Curr Biol. 24:766-73.

4Belle MD, Hughes AT, Bechtold DA, Cunningham P, Pierucci M, Burdakov D, Piggins HD. (2014). Acute suppressive and long-term phase modulation actions of orexin on the mammalian circadian clock. J Neurosci. 34:3607-21.


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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011208/1 30/09/2015 29/09/2023
1791555 Studentship BB/M011208/1 30/09/2016 30/03/2021 Sarika Paul
Description Every physiological process in your body undergoes a daily variation over the 24hr day. In mammalls these are controlled by one principal brain region the suprachiasmatic nucleus of the hypothalamus (SCN). In turn this brain region has its own electrical activity pattern that varies over the 24hr day.
Within this project we are attempting to understand how this brain region exerts it's control. in order to do that, we have used techniques including opto- and chemo- genetics, to selectively activate/inhibit populations of neurons (specifically VIP neurons) in the SCN.
These techniques have enabeled us to establish that the VIP SCN neurons drive inhibitions in a downstream brain area, shaping the 24hr activity profile of this responsive population. We have also established that VIP SCN neurons are implicated in the control of corticosterone and heartrate, as manipulation of these neurons causes acute changes in these physiological parameters.
Exploitation Route This work lays the ground work for establishing the precise ways in which SCN VIP cells exter their control over physiology.
Sectors Other