Expired on: Aug 30, 2019

Primary Supervisor: Prof. Marit W. Anthonsen, Norwegian University of Science and Technology, Trondheim, Norway
Title: Changes in metabolic pathways associated with type III IFN-mediated signalling by pneumoviruses in mucosal cells
Collaborators: Prof. F. van Kuppeveld, University Utrecht, The Netherlands; Dr. N. Manel, Stimunity, Paris, France

Interferons (IFNs) are produced in response to virus infection and induce an antiviral state in virtually all cell types. In addition to upregulating the transcription of genes that inhibit virus replication, IFNs also act to orchestrate the adaptive immune response to virus infection, important for vaccine strategies. Recently a new family of antiviral cytokines, the type III IFNs, has been identified. These IFNs are critical for the antiviral defense at mucosal surfaces, such as the airways, but the induction and action of type III IFNs are poorly understood. The cellular response to Pneumovirus involves changes in the assembly and activation states of proteins that are located at mitochondria, peroxisomes and cytoplasmic stress granules. Recent evidence has shown that bacteria is able to affect metabolism downstream of pathogen recognition. Likewise, the synthesis and effects of type I IFN depend on specific metabolic changes. However, the metabolic changes regulating type III IFN induction and action are not known. The purpose of this project is to investigate how Pneumovirus affects cellular metabolism that drives type III IFN expression and if peroxisomes and stress granules, metabolic compartments regulating antiviral defense mechanisms, are involved in the process. Moreover, we will determine if boosting the innate immune protein STING can change host metabolism for improved antiviral effects. For this purpose we will make use of Seahorse technology and RNA sequencing to determine changes in metabolic pathways, chemical inhibitors and CRISPR/Cas technology /RNA interference to target metabolic pathways, confocal microscopy to study compartmentalized signaling, and STING-activating virus-like particles to trigger innate immune signaling.

Type of Contract: Temporary (36 months)
Status: Full-time (38 hours/week)
Specific Requirements for the project
Prospective PhD candidates have a MSc in Biology, Biomedical Sciences, or a related field of study. They have strong knowledge of infectious diseases and the immune system and are highly motivated to perform ground-breaking research at the international forefront at the cross-roads of these areas.
Organisation/Institute Contact Data
Research lab: Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Norway
Contact Primary Supervisor: Prof. Dr. M. Anthonsen; marit.w.anthonsen@ntnu.no
website: https://www.ntnu.edu/employees/marit.w.anthonsen

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