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

Project description

Investigating the molecular basis of essential amino acid deprivation responses in humans

Humans, like many animals, cannot efficiently synthesise essential amino acids (eAA). The EU-funded Body2Mind project will investigate the molecular mechanisms involved in the metabolic and behavioural responses to eAA imbalance, focusing on protein appetite. To achieve this, the project's scientists will use a novel high-throughput RNA sequencing technique to decipher tissue-specific translational changes following eAA deprivation. Via a bioinformatics approach, they will explore the processes behind these changes. Finally based on their discovery of the common biological pathways underlying the response to all eAA deficiencies in the Drosophila gut, they will test the relevance of these pathways to protein feeding and to the physiological response to eAA deficiencies in humans.

Objective

"The quality and quantity of consumed nutrients, including proteins, has a significant impact on health and lifespan across
phyla. Essential amino acids (eAAs) are an extreme case, as many animals, including humans and Drosophila, cannot
efficiently 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."

Call for proposal

H2020-WF-2018-2020

See other projects for this call

Sub call

H2020-WF-03-2020

Coordinator

FUNDACAO D. ANNA DE SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Net EU contribution
€ 159 815,04
Address
AVENIDA BRASILIA, CENTRO DE INVESTIGACAO DA FUNDACAO CHAMPALIMAUD
1400-038 Lisboa
Portugal

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Region
Continente Área Metropolitana de Lisboa Área Metropolitana de Lisboa
Activity type
Research Organisations
Links
Total cost
€ 159 815,04