An omics analysis of genetic sleep loss in C. elegans

by Anastasios Koutsoumparis
Doctoral thesis
Date of Examination:2020-11-09
Date of issue:2020-11-24
Advisor:Dr. Henrik Bringmann
Referee:Prof. Dr. Ralf Heinrich
Referee:Prof. Dr. Henning Urlaub
Persistent Address: http://dx.doi.org/10.53846/goediss-8314

 

 

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Abstract

English

Sleep is a state of consciousness that has persisted through evolution and has become a necessity for animal welfare. In humans sleep loss has been shown to be inextricably intertwined with poor health. The prevalence of sleep defects in elderly people not only associates sleep quality with aging, but also draws attention to an underrated problem that will continue to affect the life quality of the increasingly aging population of the western world. Sleep regulates energy metabolism and higher brain functions. Little is known about the precise molecular mechanisms that control and are controlled by sleep, even though it has been extensively studied, due to its complex nature. In this thesis, I used the nematode C. elegans, which is a simple, yet complex enough model organism in order to discover the downstream processes that are regulated by sleep. Although sleep is connected to development in C. elegans, I used sleep loss in L1 arrested worms, as a model that couples sleep, metabolism and aging phenotypes. This is more relevant to mammal physiology than developmental sleep. By genetically ablating the sleep-active neuron RIS and recruiting powerful omics techniques, I was able to identify those components of C. elegans physiology that are affected by sleep loss. I complemented the omics experiments with extensive genetic screening for sleep alterations in animals with defects in metabolic pathways, lifespan, egg-laying and other assays. I was able to discover that sleep loss causes tissue-specific changes, reduces body size and increases the basal metabolic rate. Furthermore, I discovered that sleep loss upregulates the unfolded protein response in the endoplasmic reticulum by upregulating relevant transcription factors. Finally, I discovered that sleep loss causes oxidative stress and I characterized components of the life-prolonging antioxidant pathways that are directly regulated by the sleepactive neuron RIS.
Keywords: C. elegans; Sleep
 
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