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Dr K Chen No more applications being accepted Competition Funded PhD Project (Students Worldwide)
Leicester United Kingdom Behavioural Biology Cell Biology Genetics Neuroscience

About the Project

Sleep is an evolutionarily conserved behaviour regulated by cellular mechanisms and environmental factors. Using animal models such as the fruit fly and mice, the cellular mechanisms that control sleep, such as circadian clock, has been studied intensely. On the other hand, less is known about how environmental factors modify sleep.

Changes in photoperiod (i.e. day length) are a daily feature of middle and high latitude environments. Adjustment of sleep-wake profiles according to the current photoperiod allows animals to maintain their temporal niches across the 24-hour day. We and others have recently showed that photoperiod modifies sleep quantity and quality in the fly (1). Moreover, such modification requires neuronal activity of photoreceptors in the fly eyes. Intriguingly extreme photoperiods were shown to modify photoreceptor activity via branches of a kinase-signalling network called the integrated stress response (ISR)(2). Cellular stressors such as protein aggregates and reactive oxidative stress trigger ISR and modulate downstream gene transcription. Furthermore, altered ISR levels in the fly neurons modify sleep, suggesting that the ISR is a potential cellular mechanism linking environmental day length to sleep.

Aim:

Using the versatile genetic and imaging tools available in the fruit fly, this PhD project aims to investigate the role of the ISR and other novel molecular mechanisms in photoperiodic regulation of sleep.

Objectives and Methods:

Experiments will be conducted under five photoperiods (from 0 to 24 hours, with 8-hour increments) to investigate the following question-oriented research objectives: 1. Which subset of photoceptors are required for photoperiod-mediated sleep changes? Using video- and infrared beam-based behaviour assays and state-of-art transgenic binary expression systems in the fly, the sleep profile of flies with activated or inhibited subsets of photoreceptors will be recorded under different photoperiods. 2. How do the neuronal activity and ISR levels of photoreceptors correlate with sleep profiles at different photoperiods? Using transgenic fluorescent reporters, the level of ISR, synaptic structural changes and synaptic release properties of photoreceptors will be recorded by confocal microscopy across several time points during the five photoperiods. 3. What molecular mechanisms in the eye report changes in photoperiod? Aggregate-prone proteins and the RNAi constructs against genes in the ISR pathways will be expressed acutely in the fly eyes to manipulate ISR levels. Fly sleep in these conditions will be recorded to investigate the role of ISR in photoperiod-mediated sleep changes. Eye transcriptomes will also be collected for the five photoperiods. The identified differentially expressed genes will be knocked down in the fly eyes via somatic-CRISPR and RNAi technology. The effect of these manipulations on sleep will be tested in order to unbiasedly identify genes associated with photoperiodic regulation of sleep.

Significance:

Photoperiod is an important environmental factor that has been shown to modify sleep quality and quantity. However, the underlying neurogenetic mechanisms remain largely unclear. Using the powerful genetic toolkit available in fruit flies, this PhD project provides a unique opportunity to begin investigating this knowledge gap. The results obtained may also offer insight into the prevalent sleep disturbances associated with the artificially extended photoperiod in modern “24-7” human society.

Entry requirements:

• Those who have a 1st or a 2.1 undergraduate degree in a relevant field are eligible.

• Evidence of quantitative training is required. For example, AS or A level Maths, IB Standard or Higher Maths, or university level maths/statistics course.

• Those who have a 2.2 and an additional Masters degree in a relevant field may be eligible.

• Those who have a 2.2 and at least three years post-graduate experience in a relevant field may be eligible.

• Those with degrees abroad (perhaps as well as postgraduate experience) may be eligible if their qualifications are deemed equivalent to any of the above

• University English language requirementsapply. https://le.ac.uk/study/research-degrees/entry-reqs/eng-lang-reqs/ielts-65

For further information please contact [Email Address Removed]

Application advice:

To apply please refer the application instructions at https://le.ac.uk/study/research-degrees/funded-opportunities/bbsrc-mibtp

You will need to apply for the PhD place and also submit your online application notification to MIBTP. Links for both are on the above web page.

Project / Funding Enquiries: For further information please contact [Email Address Removed]

Application enquiries to [Email Address Removed]

Informal enquiries to Dr Ko-Fan Chen, [Email Address Removed] and see more information about the lab: https://sites.google.com/view/kofanchen


Funding Notes

All MIBTP students will be provided with a 4 years studentship.
Tuition Fees at UK fee rates
- a tax free stipend of at least £15,295 p.a (to rise in line with UKRI recommendation)
- a travel allowance in year 1
- a travel / conference budget
- a generous consumables budget
- use of a laptop for the duration of the programme

References

1. K. F. Chen, S. Lowe, A. Lamaze, P. Kratschmer, J. Jepson, Neurocalcin regulates nighttime sleep and arousal in Drosophila. eLife. 8 (2019), doi:10.7554/eLife.38114.

2. A. T. Moehlman, A. K. Casey, K. Servage, K. Orth, H. Krämer, Adaptation to constant light requires Fic-mediated AMPylation of BiP to protect against reversible photoreceptor degeneration. eLife. 7, e38752 (2018)


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