Please Note: The main page lists projects via BBSRC Research Theme(s) quoted and then relevant Topic(s).
Identifying the neurogenetic network underlying visually-driven sleep
Secondary Supervisor(s): Professor Charalambos Kyriacou, Dr Mark Hanson (Exeter)
University of Registration: University of Leicester
BBSRC Research Themes: Understanding the Rules of Life (Immunology, Microbiology, Neuroscience and Behaviour)
Project Outline
Sleep is conventionally thought to be “by the brain and for the brain”. Yet, recent laboratory studies suggest sleep, immune system, and gut health regulate each other. This interaction between gut/immunity and sleep is less well understood in the wild. Seasonal and ecological variation exists for Drosophila immune genes1, gut microbiota2, and ecological traits such as body colour3,4. Experiments using the genetic workhorse Drosophila melanogaster have further tied sleep to immune function and microbe control5. Importantly, sleep in the wild requires temporal alignment to annual transitions in photoperiod and temperature, which correlates with seasonal variation in immunity, the microbiota, and body colour. Whether genetic or microbiota variation contributes to seasonal sleep profile, or vice versa, is unclear.
Temperate Drosophila fly species encounter seasonal transitions of photoperiod and temperature across generations, providing an ideal model for understanding the temporal regulatory mechanisms underlying seasonal adaptation of sleep. Unlike D. melanogaster, D. testacea is a temperate mushroom-breeding fly occurring primarily in the late summer & fall, with different colour morphs showing seasonal3,4 and geographic3 patterns (Fig.1).
We have isolated wild-caught D. testacea lines with heritable colour variation, suggesting this seasonal body colour involves a genetic component. Recently, Hanson et al showed that D. testacea has lost a crucial immune gene, Diptericin B (DptB), which evolved to supress Acetobacter infection in fruit-feeding Drosophila. This loss may reflect the dietary switch to fungi since Acetobacter is abundant in gut microbiota of fruit-feeders, but almost non-existent in mushroom-feeding Drosophila2. Increased gut Acetobacter is associated with reduced sleep in D. melanogaster. Intriguingly, we have found that DptB mutation in D. melanogaster also causes reduced sleep, and D. testacea sleep profile differs markedly from D. melanogaster.
Taken together, the Drosophila system boasts the powerful genetic tools of D. melanogaster, as well as natural variation in immune genes, gut microbes, seasonal photoperiod and temporal sleep profile. Using these tools, we will test if the sleep-controlling role of gut microbes relies on interactions with host immune genes and/or other factors.
Aims
To address the knowledge gap, this collaborative PhD project aims to apply behaviour assays, and manipulations of the microbiota and host genetics in D. melanogaster and D. testacea. There are three research aims:
1. Identifying the role of microbiota in DptB-mediated sleep. This objective focuses on D. melanogaster. The student will use the available versatile D. melanogaster tools to clarify the neurophysiological and molecular mechanism underlying DptB-mediated sleep.
2. Establishing the sleep-wake profile in D. testacea. The student will apply video and infra-red based tracking systems6 toassay adult D. testacea sleep across genetically distinct isolines exposed to seasonally-relevant photoperiods and ambient temperatures during development.
3. Establishing the relationship between the microbiota and sleep. Gnotobiotic experiments manipulating the presence/absence of different bacteria will establish these species’ microbiome profiles & measure how key microbes affect D. melanogaster and D. testacea sleep. Available D. melanogaster transgenic lines, and even novel D. testacea transgenic lines, can further verify the effect of DptB on the gut microbiota and sleep.
In summary, this PhD project will be the first of its kind to explore the mechanistic interaction of seasonality, sleep-wake behaviour and the microbiota (Fig.1) using a predominantly genetic approach.
Techniques
Techniques that will be undertaken during the project:
The project will be conducted in two sites: At the Chen and Kyriacou laboratories (Leicester), the student will apply state-of-art infra-red and video-based behaviour tracking and analysis (DAM, DART and Ethoscope), as well as a versatile toolkit of Drosophila genetics. At the Hanson laboratory (Penryn), the student will conduct microbiome collections, bioinformatic analyses, and gnotobiotic experiments. The student may also have opportunity to conduct novel transgenesis in D. testacea.
References
1. Proc B 285, doi:10.1098/rspb.2017.2599.
2. Science 381, doi:10.1126/science.adg5725.
3. An. ESA 85, 671-685, doi:10.1093/aesa/85.6.671.
4. Jour. Fac. Sci. Hokkaido Univ.VI, Zool. 21 (1),1977. 21-30.
5. Science 363, doi:10.1126/science.aat1650.
6. eLife, 8, e38114.
