Primary supervisor: Dr. A. Bergthaler, The Research Center for Molecular Medicine (CeMM), Vienna, Austria
Title: Investigation of cytokine-induced metabolic rewiring of the liver in chronic viral infections
Collaborators: Prof. C. O`Farrelly (Trinity College Dublin, Ireland); Dr. N. Manel (Stimunity, Paris, France)
Early Stage Researcher, TBA (add once Early Stage Researcher list final)
Inflammatory processes are tightly linked to metabolic pathways including secreted metabolites and cytokines. The liver is the central organ for metabolism and a hotspot for receiving, processing and distributing local and systemic signals. Yet, comparatively little is known about the metabolic-inflammatory crosstalk at the whole organism level. The proposed PhD project will characterize and delineate interconnected pathophysiological processes with a primary focus on the liver. Systems-level and hypothesis-driven approaches are integrated to identify novel regulatory nodes between metabolism and inflammation. The project will benefit from the combination of benchmark mouse models for chronic infection, cutting-edge technologies such as viral reverse genetics, RNA-seq, metabolomics and metabolite tracing and a multi-pronged focus on systemic immuno-metabolism in vivo. Together with primary cell culture systems and bioinformatic integration of available datasets from other animal models and patients through collaborations and/or the public domain, this project is expected to unravel key parts of the complex interplay between innate cytokine signaling and liver metabolism, which in turn may affect adaptive CD8 T cells and other immune effector cells. Elucidation of the pathophysiological roles of such novel immunoregulatory networks will provide an in-depth mechanistic understanding of pathogen control, inflammation and tissue pathology. This may result in the identification of novel therapeutic targets to ameliorate and/or prevent immunopathologies in infectious and inflammatory diseases.