Molecular neurobiology of circadian clocks in the mammalian brain
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Our lives are built around daily (circadian) cycles of behaviour and metabolism, the rhythm of sleep and wakefulness being the most pervasive. Well ordered circadian rhythms are a pre-requisite for both physical and mental health, such that disturbances of them are associated with many forms of illness, both metabolic (e.g. obesity and diabetes) and psychiatric (e.g. depression and schizophrenia).
The principal co-ordinator of circadian rhythms is the suprachiasmatic nucleus (SCN) of the hypothalamus: this is the dominant circadian clock of the brain, using a molecular genetic feedback loop that can define approx. 24h cycles indefinitely. But how does this cluster of 10,000 clock neurons and astrocytes work at a molecular level, and how does it send out timing signals to control the rest of the brain and body? This project will apply state-of-the-art microscopy and viral gene delivery alongside both in vivo (behavioural, physiological) and in vitro (organotypic brain slice imaging techniques) approaches. It will exploit genetically modified mice, including lines carrying constitutive and conditional, circadian and neurochemical genetic mutations, combined with bioluminescent and fluorescent imaging and optogenetic and chemogenetic manipulation. The application of novel means of genetic code expansion [Ernst et al. Nat Chem Biol. (2016)] to interrogate the molecular clockwork will be an important feature.
The project will provide a sound training in molecular and systems neuroscience. The successful candidate will work within a multidisciplinary research group with a strong international reputation in circadian clock neurobiology, and will also enjoy productive interactions with other research groups in the Neurobiology Division and the wider LMB.
Recent first-author papers from PhD students in Hastings group:
- Edwards et al. PNAS (2016).
- Smyllie et al. PNAS (2016)
- Smyllie et al. Current Biology (2016)
Brancaccio et al. (2017).
Ernst et al. (2016).
Nat Chem Biol.
Militi et al. (2016).
Parsons et al. (2015)
Brancaccio et al. (2013)