How does a need turn to a want: using Drosophila melanogaster to identify how the gut-brain axis mediates protein appetite

The quality and quantity of consumed nutrients, including proteins, has a significant impact on health and lifespan acrossphyla.

Essential amino acids (eAAs) are an extreme case, as many animals, including humans and Drosophila, cannotefficiently synthesize them, and thus relay solely on protein intake to obtain them. Thus, understanding the molecular changes mediating the organism´s response to such an imbalance is highly important.

It is established, that animals respond to a single eAA deficiency behaviorally and metabolically.

Evidently, the organism recognizes eAAs-imbalance and translates it into a specific foraging behavior and feeding decisions appropriate for compensating for such specific nutrient deficiency (i.e increased protein preference and feeding). How this is done however remains elusive.

We hypothesize that this nutrient imbalance drives molecular changes that are ""mirrored"" in gene transcription in order to drive the response to eAA imbalance, in a tissue specific manner.

In this project we will unravel molecular mechanisms involved in the metabolic and behavioral responses to eAAs imbalance , while focusing on protein appetite, in a comprehensive manner.

To achieve this, we propose to employ a novel high-throughput RNA sequencing method to decipher tissue specific translational changes following eAAs deprivation. Using a bioinformatic approach, we will look into the processes underlying these transcriptional changes.

Interestingly, preliminary data already reveals common biological pathways underlying the response to all eAA deficiencies the fly gut.

We will genetic approaches to test the relevance of these pathways to protein feeding and to the physiological response to eAA deficiencies.

We foresee this project to open an essential next step in nutritional- neuroscience research, with potential to further our knowledge about the link between stomach, gut and brain signals in driving nutrient homeostasis.