Miguel-Aliaga LabGut Signalling and Metabolism

Research

About our research work

Internal organs are constantly exchanging signals, and can undergo profound anatomical and functional changes in response to them, even in fully developed organisms. Such organ plasticity results from a need to integrate and respond to both environmental information and internal state, and is key to maintaining homeostasis and driving adaptive changes. We are interested in understanding the mechanisms by which organs sense change and respond to it: the molecules, cellular events and physiological adaptations involved. The intestine and its neurons are a fantastic system with which to tackle these questions.

Current projects

Our ongoing work is exploring these topics:

Sex differences in the intestine

Combining transcriptional and genetic approaches, we found a new sex differentiation pathway in adult gut somatic stem cells (Hudry et al (2016) Nature). It governs sex differences in organ size, plasticity during reproduction and its response to tumorigenic insults. We are exploring additional sex differences in other intestinal cell types.

Functions of enteric neurons

Our ongoing characterisation of the different neuronal types innervating the intestine has already revealed their key roles in regulating food intake, fluid balance, renal function and mating-triggered intestinal adaptations (Cognigni et al (2011) Cell Metab, Talsma et al (2012) Proc Natl Acad USA).

The plasticity of the intestinal epithelium

We have found that the intestinal epithelium of females is resized and metabolically reprogrammed during reproduction. Intestinal remodelling is mediated by juvenile hormone released after mating, and is required to sustain reproduction – or, as Alex Shingleton put it, females have the guts for reproduction! (Reiff et al (2015) eLife, Shingleton (2015) Curr Biol).

Neuron/trachea interactions

We have found that the nutrient-driven remodelling of enteric trachea (tubes that, like our vascular system, deliver oxygen to intestinal cells) drives metabolic adaptations to malnutrition that enhance survival (Linneweber et al (2015) Cell). We now wonder how changes in the branching of enteric trachea are sensed and decoded by the intestine to drive these metabolic adaptations.

How we do it

Our main model system is Drosophila melanogaster, but we are beginning to explore the evolutionary conservation of some of our findings in mice and humans through local and international collaborations.

Our research is conducted in brand new laboratories and fly facilities, and is supported by a range of core facilities, including genomics, bioinformatics, proteomics and imaging.

We are core-funded by the MRC, and receive additional funding from the ERC, EMBO and BBSRC.