Project description:Colonial tunicates are the only chordates that regularly regenerate a fully functional whole body as part of their asexual life cycle, starting from specific epithelia and/or mesenchymal cells. In addition, in some species, whole-body regeneration (WBR) can also be triggered by extensive injuries, which deplete most of their tissues and organs and leave behind only small fragments of their body. In this study we characterized the onset of WBR in Botryllus schlosseri, one colonial tunicate long used as a laboratory model. We first analyzed the transcriptomic response to a WBR-triggering injury. Then, through morphological characterization, in vivo observations via time-lapse, vital dyes, and cell transplant assays, we started to reconstruct the dynamics of the cells triggering regeneration, highlighting an interplay between mesenchymal and epithelial cells. The dynamics described here suggest that WBR in B. schlosseri is initiated by extravascular tissue fragments derived from the injured individuals rather than particular populations of blood-borne cells, as has been described in closely related species. The morphological and molecular datasets here reported provide the background for future mechanistic studies of the WBR ontogenesis in B. schlosseri and allow to compare it with other regenerative processes occurring in other tunicate species and possibly independently evolved.
Project description:Morphological and molecular investigations on Cryphonectria parasitica isolates attacking chestnut in Basilicata Region (Southern Italy)
Project description:Molecular glue degraders (MGDs) are small molecules that degrade proteins-of-interest via the ubiquitin-proteasome system. Historically, MGDs were discovered serendipitously. Current approaches for MGD discovery include cell-viability based drug screens or data mining of public transcriptomics and drug response datasets. The explored target space is consequently re-stricted to the essential proteins. Here we develop a high-throughput workflow for MGD discovery that also reaches the non-essential proteome. This workflow begins with the rapid synthesis of a compound library by Sulfur(VI) Fluoride Exchange chemistry coupled to a morphological profiling assay in isogenic cell lines that vary in levels of the E3 ligase CRBN. By com-paring the morphological changes induced by compound treatment across the isogenic cell lines, we were able to identify FL2-14 as a CRBN-dependent MGD targeting the non-essential protein GSPT2. We envision that this workflow would con-tribute to the discovery and characterization of MGDs targeting a wider range of proteins.