EMBL Seminars

Abstract:

I am interested in how information is encoded at the multi-organ level. Working at the interface between physiology and developmental biology, we have explored the “continued development” of adult organs. We have sought to understand how and why organs such as the intestine grow, shrink and are metabolically remodelled even in adult, fully developed animals, and how this plasticity differs between the sexes. We have tackled these questions across biological scales, initially in Drosophila and more recently in mice and humans. Our worked has uncovered new mechanisms of sex differentiation as well as previously unrecognised communication between gut and gonads that impacts food intake, gamete production and tumour susceptibility. Some of our work has also investigated how the intestine senses and responds to nutrients: we discovered an intestinal zinc sensor that promotes Tor signalling to sustain food intake and developmental growth. I have now become very interested in the idea that there is a logic to the shape and arrangement of organs within the body cavity. We have developed new methods to visualise and quantify organs in 3D in their natural environment. We can now interrogate these multi-organ configurations to ask how organ shape impacts organ function and that of its neighbours, and whether organ geometry enables or confines communication across organs.

Connection details
Zoom*: [https://embl-org.zoom.us/j/96374261689?pwd=TnNxRWtQY2lyc2pSa2JpY3NGcDlhZz09] (Meeting ID: [963 7426 1689], Password: [DBU])

Abstract

Epigenetic components regulate many biological phenomena during development and normal physiology. When dysregulated, epigenetic components can also accompany or drive diseases. One main class of epigenetic components are Polycomb group proteins. Originally, Polycomb proteins were shown to silence gene expression. We found that this function involves the regulation of 3D chromosome folding and we found that Polycomb components can induce the formation of long-distance interactions or chromatin loops that may play instructive roles in gene regulation as well as serve as scaffolding elements that contribute to enhancer-promoter specificity. Perturbation of Polycomb components is involved in human cancer and leads to tumorigenesis in flies. Surprisingly, even upon a transient depletion followed by restoration of the full Polycomb compendium, epithelial cells lose their normal differentiated fate, continue proliferating and establish aggressive tumors, demonstrating that cancer can have a fully epigenetic origin. Similarly, transient perturbation of histone acetylation in mouse ES cells and gastruloids shows that they can record chromatin changes and that this results in cellular memory of the perturbation states. The implication of these data will be discussed.