The adult mammalian stomach can be divided into three distinct parts: From the proximal fore-stomach over the corpus to the distal pylorus. Due to constant exposure to mechanical stress and to hostile contents of the lumen, highly specialized cell types have to be constantly reproduced in order to maintain the function of the gastrointestinal tract. Recently, the applicant identified Troy+ chief cells as a novel stem cell population in the corpus epithelium. Troy+ chief cells displayed a very low proliferation rate indicating their quiescent nature compared to other known gastro-intestinal tract stem cells. Interestingly, these stem cells can actively divide upon tissue damage, suggesting distinctive statuses under conditions of homeostasis and injury. As Troy+ stomach stem cells exhibit interconvertible characteristics i.e. quiescent and proliferative, they represent a unique model of adult stem cells with which we can study 1) the dynamics of stem cell propagation in homeostasis and regeneration and the underlying mechanism of this switch by analysing molecular and epigenetic profiles. Subsequently, by analysing mRNA expression profiles and epigenetic changes in Troy+ stem cells between homeostasis and injury repair, we will generate a list of genes with potentially interesting functions in cell fate decisions. We will therefore investigate 2) the stomach stem cell programme in homeostasis and regeneration using in vitro and in vivo functional genetics. Lastly, we will characterise 3) human stomach stem cells in normal and pathological conditions. Here we pursue three main aims: - Investigating Troy+ stem cell dynamics during homeostasis and injury repair - Unmasking the stomach stem cell programme using in vitro and in vivo functional genetics - Characterising human stomach stem cells

The ongoing arms race between transposable elements and their host organisms is a central driver of genetic innovation and biological diversity. Yet, despite this crucial role, the underlying principles that govern transposon-host interactions remain poorly understood. The ERVolution project aims to gain critical insights into the evolutionary dynamics and rules of the ancient transposon-host conflict. The project focuses on the Drosophila ovary ecosystem and the diversification of insect endogenous retroviruses (ERVs), a highly successful group of genome parasites that have acquired the ability to invade germ cells from surrounding somatic cells as viral particles to multiply in the germline genome. Through a multidisciplinary approach that combines host and transposon genetics, single-cell genomics, machine learning, and controlled transposon invasion experiments, we will investigate how transposon-host interactions create biological diversity by driving molecular innovations on both sides. Specifically, the project aims to uncover (i) how infectious ERVs exploit cell biological processes in the host gonad for their soma-to-germline transmission, (ii) how ERVs diversify their compact cis-regulatory elements to optimally adapt their expression to the host, and (iii) how the host transposon defence system exploits an Achilles' heel of ERVs, their unusual nucleotide composition, to silence both old and new genome invaders. The ERVolution project provides a unique opportunity to uncover general principles of transposon-host interactions by studying the molecular and evolutionary processes of a major battle between multiple transposons and an experimentally accessible host model organism. The project’s results are expected to have far-reaching implications beyond Drosophila, particularly in the fields of retrovirology, the evolution of cis-regulatory sequences of transposons, and the fundamental question of how eukaryotic cells distinguish their own from foreign RNA.

The European Consortium for Communicating Gene and Cell Therapy Information (EuroGCT) unites 49 partner organisations and institutions across Europe, including the major European advanced therapies learned societies, with the common goal of providing reliable and accessible information related to cell and gene therapy development to European stakeholders. EuroGCT has two major objectives: • To provide patients, people affected by conditions, healthcare professionals and citizens with accurate scientific, legal, ethical and societal information and with engagement opportunities, and thus to support better informed decision-making related to cell and gene-based therapies. • To facilitate better decision-making at key points in development of new therapies and thus enable improved product development, by providing the research community and regulatory and healthcare authorities with an information source on the practical steps needed for cell and gene therapy development. To achieve our aims, EuroGCT will adopt a highly structured system for coordinated management of information related to cell and gene therapy development and, from this, will implement an ambitious programme of online and direct stakeholder information provision and engagement. All outputs will be delivered in 7 European languages, to ensure broad accessibility, and will be rigorously evaluated against measurable objectives throughout the project duration. The proposed consortium comprises leading cell and gene therapy-related organisations and basic and clinical research labs across Europe, including new member states; together with experts in product development, ethical, legal and societal issues, and in evaluating clinical outcomes; patient representatives; and science communicators. It thus is uniquely placed to develop a world-leading cell and gene therapy information resource and to meet the challenge outlined in Topic SC1-HCO-19-2020.