ppGpp in flies: a molecule connects sleep and starvation

Sleep is an essential behavior that exists from worms to humans, and it’s driven by integration both internal sleep drive and external environment factors. However, its mechanisms remain elusive. Scientists from Peking University, China have discovered a hidden player in the world of fruit fly sleep—ppGpp, a molecule originally known for its role in bacterial stringent responses to amino acid shortage. Led by Dr. Yi Rao, Dr. Xihuimin Dai, and Dr. Wei Yang, the team uncovered a link between ppGpp and sleep regulation in fruit flies, and thatppGpp is involved in the connection between sleep and starvation.

Through a forward genetic screen of ~2000 mutant flies, the researchers found a strain of fruit flies with unusual sleep patterns, marked by less nighttime sleep and longer time to fall asleep. This behavior was causedbymutation of a gene called Mesh1, which turned out to be involved in ppGpp degradation in fruit flies.

Although ppGpp was known for its role in bacteria, its existence and function in animals were unclear. This study showed that not only is ppGpp present in fruit flies, but it also plays a role in regulating their sleep. Furthermore, ppGpp is involved in Sleep Induced Sleep Loss (SISL) in flies-----Mutations in Mesh1 made the sleep loss worse during starvation, while increasing Mesh1 helped reduce it.

They then pinpointed the specific part of the fruit fly brain where ppGpp works to regulate sleep and SISL—called pars intercerebralis (PI), especially Dilp2 (Drosophila insulin like peptide 2)-expressing neurons in PI. Interestingly, previous studies have shown that Dilp2 expressing neurons are important to SISL regulation.

In short, this study reveals that ppGpp, a moleculein bacterial stringent response, plays a surprising role in how fruit flies sleep, especially when they're hungry. Understanding this connection could offer insights into how sleep is influenced by external factors, opening the door to new discoveries about the connection between sleep and hunger in animals and possibly in humans too.