Developmental and cellular mechanisms that underlie regeneration and slow aging in Hydra
Description: <p>Hydra is a small invertebrate polyp that together with jellyfish, corals and sea anemones belongs to the phylum named Cnidaria. Hydra is known for its amazing ability to regenerate any missing part of its body after amputation, a property that relies on the ability of the regenerating tip to form a head organizer. Organizers are localized areas that after transplantation onto a host, trigger the growth of ectopic structures by recruiting cells from the host through growth factors and secreted substances they produce. The head organizer can be found in intact Hydra at its apex, embedded in a highly differentiated tissue. This “homeostatic” head organizer is necessary to maintain the anatomy of intact adult animals. By contrast in the regenerating tip, the organizer is “developmental”, formed de novo after bisection, localised in a highly proliferative region, and triggering the complete patterning of the regenerating head. </p><p>Here, we plan to characterize and compare the molecules that regulate the activity of both types of head organizers, homeostatic and developmental. Of special interest will be the proteins that act positively or negatively on molecular components of head organizer previously identified such as the components of the Wnt/beta-catenin signaling pathway (head inducer) or the transcription factor Sp5 (head inhibitor). These candidate regulators will be over-expressed in Hydra as well as in mammalian cells to ultimately deduce the genetic circuitry that support these two types of head organizer activities. Understanding how a developmental organizer can form upon injury in a naïve gastric tissue, get stabilized to become a homeostatic organizer is a fundamental knowledge in developmental and cell biology. It will tell us how an adult tissue can maintain a high developmental plasticity, i.e. the ability to reactivate a developmental program, a key question linked to regeneration. </p><p>Hydra is also characterized by large stocks of stem cells that are continuously renewed by division. In this project, we propose to characterize the links between two properties of Hydra epithelial stem cells, their unique cell cycle characterized by a short G1 phase and a long pause in the G2 phase, and a high resistance to cell death. These cell cycle properties are also found in some mammalian epithelial stem cells, including cancer stem cells. We plan to produce transgenic lines that express a biosensor of the cell cycle to visualize the different phases of the cell cycle in real conditions. This new tool will allow us to test resistance to cell death at different phases of the cell cycle and to better characterize the regulators of epithelial resistance to cell death. These candidates will be tested on mammalian cells as well as on aging and non-aging animals. With this strategy, we will be able to better understand the mechanisms of resistance to cell death, a major issue in cancer treatments.</p>
Amount: CHF 945,000
Funding type: research
Funder scheme: Project funding
Start date: 2019-11-01
End date: 2024-03-31
Investigator: Galliot, Brigitte
Institution: University of Geneva – GE
Subfield: Paleontology
Field: Earth and Planetary Sciences
Domain: Physical Sciences
Funded outputs count: 9
Funder award ID: 189122
OpenAlex ID: G889853771