The intestine physically touches the reproductive organs, and that contact may be as important as the chemical signals they exchange. Researchers have long known that the gut sends signals that control appetite, metabolism, and reproduction, but they have assumed those signals travel through the bloodstream. This project tests a different idea: that organs are arranged inside the body in a precise spatial pattern that determines which ones can talk to each other, and that the gut’s shape and position actively enable or block those conversations. Using 3D imaging of fruit flies, the team will build detailed maps of the intestine and its neighbours, then use genetic tools to identify the molecules that create and maintain this geometry. They will also apply the same approach to tsetse flies, which give birth to live young—a rare reproductive strategy in insects and a trait that makes them devastating disease vectors. This is fundamental science. If it succeeds, it will reveal a previously unrecognised layer of biological organisation—how the physical layout of organs shapes their communication. That knowledge could eventually inform new strategies for controlling insect populations that transmit disease, but the immediate value is in resolving basic paradoxes about how organs coordinate whole-body physiology.
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I have a long-standing interest in the intestine as a major source of signals that maintain whole-organism homeostasis and drive adaptive change. We recently discovered that the intestine engages in bidirectional communication with reproductive organs, revealing a novel gut-gonad axis that impacts food intake and gametogenesis. During the course of these experiments, we observed intriguing adjacency between organ regions that communicate with one another, raising the possibility that inter-organ communication is confined in space as well as time. In this proposal, I explore the idea that there is a spatial logic to how internal organs are arranged within the body cavity of animals, and that their geometry can both enable and confine inter-organ signalling. Using 3D images of adult Drosophila, we will gather volumetric data, building detailed 3D maps of the intestine and neighbouring organs. This will enable us to develop new quantitative methods to describe gut geometry and its inter-organ contacts, studying their stereotypy, variation amongst individuals and relationship with internal state. We will then use the powerful genetic toolkit available in Drosophila to identify the molecular mechanisms that make and maintain 3D intestinal geometry. With this multipronged approach, we will unpick this previously unrecognised level of organisation, and establish its roles in enabling and/or confining interorgan communication. Finally, we will apply our methodologies to investigate contributions of the intestine and its geometry to the viviparity of tsetse flies: an under-investigated form of reproduction in a biomedically relevant and economically damaging disease vector. By revealing a previously unrecognised level of biological complexity, we will help resolve current paradoxes in inter-organ signalling, shed new light on the physiology of organs and organisms, and explore the potential of gut-gonad communication as a novel population control strategy.
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