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

Project Information

Body2Mind

Grant agreement ID: 101038098

DOI

10.3030/101038098

Project closed

EC signature date 1 April 2021

Start date 1 October 2021

End date 27 April 2024

Funded under

• SPREADING EXCELLENCE AND WIDENING PARTICIPATION

Total cost

€ 159 815,04

EU contribution

€ 159 815,04

Coordinated by

FUNDACAO D. ANNA DE SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Portugal

Periodic Reporting for period 1 - Body2Mind (How does a need turn to a want: using Drosophila melanogaster to identify how the gut-brain axis mediates protein appetite)

Reporting period: 2021-10-01 to 2023-09-30

Summary of the context and overall objectives of the project

Quality and quantity of nutrients are key determinants of health and lifespan across phyla. Dietary proteins are of particular importance as many animals, including humans and Drosophila, cannot efficiently synthesize some of proteins´ building blocks, namely, essential amino acids (eAAs). Thus, animals and humans relay solely on protein intake to obtain them. However, each eAAs has different physiological roles and different effects on health-span. In order to overcome protein imbalance, animals can change their feeding strategy to increase protein consumption, even when only a single eAA is missing in their diet. However, the cellular and molecular processes leading to change in feeding preference to a specific food source upon a protein deficiency are still unknown. In this project our aim was to uncover the process of translating the need for any single eAA to a goal direct behavior towards foraging and consuming proteinaceous foods. The behavioral adaptation to diettary imbalance and the physiological importance of eAA are highly conserved, and gene regualtion is highly translatable across species. Thus, the identified mechanisms from this project shed light on global process underlying protein-related dietary perturbations and the relavant behavioral adaptations.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In this project we have used synthetic diet to eliminate single eAAs from the flies´ diet, followed by RNA-sequencing to learn about the change in gene transcription in response to the dietary pertubations. We have identified the common and the uniquely regulated genes following each eAA pertubation, gaining further understanding of the role of specific eAAs only possible on a large scale project such as this one. Furthermore, we have found that at least two olfactory genes show higer expression levels in deprived flies, under all eAA depletions. By using our tracking assay, we assessed the functional relevance of these two olfactory genes to foraging and feeding. Interestingly, we have found that this increased olfactory-genes expression leads the flies not only to increase interaction with proteinacious food, but also to increased approaches towards specific gut bacteria, that might help it cope with the dietary pertubation. These processes are likely to be relavant for a wide variety of species and can be used for pest control on the one hand and on the other hand shed light on dietary choices and behavioral adaptations in response to food availability and consumption.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The roles of different eAA on cellular functions is a subject for research for a very long time. However, the impact of eAA pertubation in an organismal level is a difficult one to tackle. Using Drosophila melanogaster, the synthetic det and novel RNA-sequencing methods have allowed us to approach this quastion and gain insight into the role of specific eAAs in a comprahansive manner. Now we have insights into eAA specific effects on the organism, in specific tissues. Publishing this descriptive dataset will have a significant impact on our understanding of eAAs.
Functional analysis of the genes identified to be impacted by dietary eAA depletion furthers our knowledge on the roles and the processes of specific eAAs and of protein-related dietary pertubations in general. In our soon to be published work we have chose to focus on 2 olfactory receptors that increased their epression following eAA depletion from the diet. Although olfactory tuning in response to starvation or protein deprivation have been described previously, identifying receptor-gene regulations in response to chnages soley in diet, with minumal to no change in enviromental conditions (i.e. internal state derived olfactory receptors regulation) were not yet described. Moreover, we have unexpectedly identified olfactory receptors that tune the flies´towards gut bacteria to be modulated by diet. This further adds to our understanding of organisms important inteactions with their microbiome. This work will soon be submitted for publication. Importantly, we have generated an online tool to access the analyzed data to allow the community and the publish to further explore how specific eAAs perturb transcription and hopefully exploit the data for further discoveries. This website will . This will, again, drive the knowledge of the field towars better uderstanding of gene ragulation and dietary-eAA or protein pertubation.

Figure 1