Molecular and Cellular Control of Tissue Homeostasis in Health and Disease - TissueHome

Human barrier tissues require continuous surveillance of their integrity, function as well as regeneration. The efficient immune surveillance of epithelial / endothelial barriers such as present in the gastrointestinal tract, in the skin or in other organs demands numerous autocrine, paracrine and long-range signaling mechanisms to coordinate complex intercellular interactions that maintain physiological tissue homeostasis. Inflammation, though a double-edged sword of immunity, constitutes a hallmark signal, which in essence determines functions of peripheral tissues. Hence, misregulation of inflammatory processes at the genetic, epigenetic as well as intercellular levels, or inborn genetic errors and pathogens can cause detrimental inflammation, thereby promoting malignant transformation, autoimmune diseases such as inflammatory bowel disease, arthritis, psoriasis or hypersusceptibility to pathogenic infections. However, many fundamental questions governing the molecular principles of immune surveillance during tissue homeostasis remain open or controversial. This doc.funds will therefore implement a new interuniversity program devoted to the competitive training of PhD students in translational research, addressing fundamental questions related to mechansims of immunological control that maintain homeostasis of barrier tissues (TissueHome). The central hypothesis of TissueHome is that malregulation of immune surveillance deranges homeostatic processes at epithelial barriers, thereby promoting infectious as well as autoimmune diseases. TissueHome will use interdisciplinary state-of-the-art translational approaches (genetics, genomics, transcriptomics, bioinformatics, molecular medicine, molecuar biology, primary immune cells, small animal models of infectious and autoimmune diseases) to address the key aims. First, understand mechanisms of signaling pathways and delineate how genetic/epigenetic regulation of immune responses operates in response to physiological / pathological stimuli. Second, decipher mechanisms of intercellular communication, and unravel how recruitment and cross-communication of adaptive / innate immune cells with endothelial / epithelial cells shapes tissue homeostasis in health and disease. Finally, how can pathogens and the interactions with immune cells affect microbiomes colonizing epithelial / mucosal tissues or the skin, and how can microbiome dysbiosis promote hypersusceptibility to inflammatory diseases. Twelve international PhD students will be identified through a highly competitive selection procedure. PhD students will address major aims through hypothesis-driven projects under the supervision by TissueHome faculty members, who are internationally leading experts with complementary expertises ranging from skin function, host-pathogen interactions, systems biology, immune signaling, microbial infections, RNA regulation, gene regulation, epigenetics, transcription, chromatin modifications, innate/adaptive immunity, cancer biology, pharmacology, inflammation, translational medicine, animal genetics, cancer multidrug resistance, microbiome & functional genomics and bioinformatics to Darwinian medicine. All PhD projects demand interdisciplinary approaches for successful answering key aims, fostered by interuniversity cooperations in TissueHome. We expect TissueHome to yield a better understanding of fundamental mechanisms governing immunological control of tissue homeostasis in health and disease. In addition, the translational approaches of TissueHome are expected to support the development of improved therapeutic strategies in the context of relevant inflammatory diseases.

The doc.funds "TissueHome" implemented a new comprehensive interuniversity doctoral program devoted to the training and education of PhD students in translational biomedical research. The central overarching hypothesis of TissueHome projects was that dysregulation of complex communication signals between immune cells derange normal immune surveillance, thus promoting inflammatory diseases, autoimmune diseases, cancer as well as microbial infections. TissueHome projects addressed how the communication within tissues shapes the immunological competence required for physiological barrier function. Furthermore, TissueHome intensified collaborations between the MeduniWien and the Vetmeduni in basic and translational research by addressing topics of medical relevance. PhD students were hired following two highly selective rounds of personal interviews. A total of eleven PhD students (8 at Meduni Wien, 3 at Vetmeduni) entered the TissueHome program, which in turn was embedded in the ongoing generic PhD training at the MeduniWien, the Max Perutz Labs (Vienna Biocenter) and the Vetmeduni. The TissueHome faculty encompassed principal investigators enjoying international reputation for their work in immune signaling, epigenetics, RNA modification, fungal infectious diseases, autoimmune diseases, molecular medicine, animal genetics, cellular and molecular immunology, host-pathogen interactions, gene regulation and bioinformatics. The individual PhD projects addressed fundamental questions related to molecular mechanisms of immune surveillance that are critical to maintain tissue homeostasis in health and disease, including cancer, autoimmunity and infections. The research approaches exploited state-of-the art methods in infection and inflammation biology, including genomic and genetic technologies, next generation sequencing, high-end imaging, animal models and mouse genetics, as well as sophisticated immunology to decipher mechanisms involved in orchestrating barrier function. Moreover, PhD students participated in a tailor-made soft skill and practical course program, ranging from media and interview training, ethics, large scale data handling to grant writing and reviewing, as well as research training visits to several TissueHome groups. TissueHome united forces with the FWF-funded doctoral program Inflammation and Immunity through bi-monthly joint progress reports and journal clubs held in digital format owing to the COVID-19 pandemic. TissueHome started out with a kick-off meeting that was held near Vienna. The PhD students of the program presented their own project outlines and obtained feedback from attending SAB members. TissueHome also held a Retreat in the Vienna woods in fall of 2021, where all PhD students presented the status of their PhD projects. Finally, TissueHome concluded with the international symposium "Immune Control of Tissue Homeostasis" that was solely organized by PhD students. Taken together, TissueHome provided a stimulating and challenging research environment for PhD students, complemented by extensive transferable skills training to prepare the PhD students for a career in academia, industry or in science-related sectors.