GutSense | Environmental control of physiology through the brain-gut axis

Summary
A series of tightly controlled processes ensure that energy is either stored or consumed within an organism. This control is central to survival and prosperity of the animal, yet we only partly understand it. Communication between the brain and the gut, the so called “brain-gut axis”, has emerged as a key player in regulating aspects of animal physiology by directly affecting energy stores. Nevertheless, due to the astonishing anatomical complexity of the underlying neural circuits in mammals, an in depth understanding of the cellular and molecular mechanisms controlling this axis is still lacking. Using the simpler yet functionally comparable Drosophila brain-gut axis as a model system, I have recently shown that adult enteric neurons are functionally plastic. This constitutes a physiological feature highly relevant for the adjustment of food intake by the animal to meet energy demands. I explored this in females in the context reproduction, where mechanisms underlying appetite regulation are evolutionary conserved across multiple species. Building on my expertise, I will now investigate the long-standing question on how environmental factors, such as dietary habits or levels of physical activity, impact the function of the brain-gut axis. For GutSense, I will leverage the unique experimental opportunities available in Drosophila to address the role of gut-neurons in metabolic adaptation: (a) characterize neurons which respond to these environmental cues, and the relevant neural circuits and mediators (b) identify the target tissues and the nature of inter-organ signals involved (c) investigate the impact of timing and duration of exposure to these factors, on metabolic adaptation. Through these, I will uncover basic and likely evolutionary conserved mechanisms and better understand the context-dependent tolerance of metabolic challenges. Such insight can lead the way in elucidating the contribution of brain-gut networks to the development of pathophysiology.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/101117267
Start date: 01-01-2024
End date: 31-12-2028
Total budget - Public funding: 1 929 674,00 Euro - 1 929 674,00 Euro
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Original description

A series of tightly controlled processes ensure that energy is either stored or consumed within an organism. This control is central to survival and prosperity of the animal, yet we only partly understand it. Communication between the brain and the gut, the so called “brain-gut axis”, has emerged as a key player in regulating aspects of animal physiology by directly affecting energy stores. Nevertheless, due to the astonishing anatomical complexity of the underlying neural circuits in mammals, an in depth understanding of the cellular and molecular mechanisms controlling this axis is still lacking. Using the simpler yet functionally comparable Drosophila brain-gut axis as a model system, I have recently shown that adult enteric neurons are functionally plastic. This constitutes a physiological feature highly relevant for the adjustment of food intake by the animal to meet energy demands. I explored this in females in the context reproduction, where mechanisms underlying appetite regulation are evolutionary conserved across multiple species. Building on my expertise, I will now investigate the long-standing question on how environmental factors, such as dietary habits or levels of physical activity, impact the function of the brain-gut axis. For GutSense, I will leverage the unique experimental opportunities available in Drosophila to address the role of gut-neurons in metabolic adaptation: (a) characterize neurons which respond to these environmental cues, and the relevant neural circuits and mediators (b) identify the target tissues and the nature of inter-organ signals involved (c) investigate the impact of timing and duration of exposure to these factors, on metabolic adaptation. Through these, I will uncover basic and likely evolutionary conserved mechanisms and better understand the context-dependent tolerance of metabolic challenges. Such insight can lead the way in elucidating the contribution of brain-gut networks to the development of pathophysiology.

Status

SIGNED

Call topic

ERC-2023-STG

Update Date

12-03-2024
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Horizon Europe
HORIZON.1 Excellent Science
HORIZON.1.1 European Research Council (ERC)
HORIZON.1.1.0 Cross-cutting call topics
ERC-2023-STG ERC STARTING GRANTS
HORIZON.1.1.1 Frontier science
ERC-2023-STG ERC STARTING GRANTS