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: Zsofia Keszei
PROJECT DESCRIPTION:
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.
