Researchers have discovered that ppGpp, a molecule originally known for its role in bacterial stringent responses to amino acid shortage, plays a crucial role in regulating sleep in fruit flies—and reveals a connection between sleep patterns and starvation.

Through a forward genetic screen of approximately 2,000 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 caused by a mutation 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, especially Dilp2 (Drosophila insulin like peptide 2)-expressing neurons in pars intercerebralis. Interestingly, previous studies have shown that Dilp2 expressing neurons are important to SISL regulation.

The results of the study are published in hLife.

In short, the study reveals that ppGpp, a molecule in 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.

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