We are interested in the plasticity of adult organs: how and why organs that we commonly regard as fully developed change in size or function in response to environmental or internal challenges.
We use the intestine and its neurons to explore these questions because they allow us to explore organ plasticity from an integrated perspective: how an organ senses and integrates signals from both its internal milieu and the environment (e.g. nutrients, microbiota), how its adult progenitors respond by either maintaining or resizing the organ, and how different cell types within the organ (epithelial, muscle, neural) communicate to achieve coordinated, organ-level remodelling.
Our work is at the interface of developmental biology and physiology. We use genetic approaches to interfere with specific gene or cell functions using genome editing and/or genetically encoded tools such as thermo/optogenetics to interfere with neuronal activity. We assess the consequences at the levels of molecules (transcriptomics, metabolomics), cells (imaging), organ (peristalsis, modelling), and whole animal (behavioural assays and physiological readouts).
We typically use Drosophila melanogaster for discovery; since the identification of adult somatic stem cells in the Drosophila intestine, there has been a surge of studies using this invertebrate organ to investigate various aspects of physiology. Like its mammalian counterpart, the digestive tract of Drosophila is functionally regionalised. It harbours a resident microbiota, and consists of cell types similar to those found in the human gastrointestinal tract, including digestive/absorptive enterocytes and hormone-secreting enteroendocrine cells.
Informed by our Drosophila work, we sometimes explore specific questions in mice (in vivo or using intestinal organoids) and/or humans – for example, when our Drosophila research suggests new or unexpected explanations for certain aspects of mammalian physiology, such as contributions of cell-intrinsic mechanisms to sexual dimorphisms in the intestine.