Primary supervisor: Dr. B. van den Hoogen, Erasmus MC, Rotterdam, The Netherlands
Title: To determine the role of Pneumovirus infection in regulation of MAVS signalling and its effect on immune- and metabolic pathways.
Collaborators: Prof. A. Bowie, Trinity College Dublin, Ireland; Dr. K. Pardalli, AstraZeneca, Gothenburg, Sweden.
Early Stage Researcher, TBA (add once Early Stage Researcher list final)
For respiratory viruses such as the Human Metapneumovirus (HMPV) , a member of the Pneumoviridae family, little is known about their interaction with the immunometabolism pathways. Elucidating knowledge on this interaction could lead to a rational design of antiviral therapies. Data so far, suggest that the M22 protein of HMPV is responsible for subverting the innate immune response by interfering withs MAVS signlalling , but other proteins and other pathways might also be involved in the mechanism. MAVS not only plays a pivotal role in the induction of antiviral and inflammatory pathways, but is also involved in the coordination of apoptotic and metabolic pathways.
Using our expertise on the molecular virology of HMPV, and a wide set of molecular, biochemical, virological and immunological techniques, ESR7 will determine the role of the Pneumovirus M2.2 protein, as well as other viral proteins, in the interaction with innate immune- and metabolic pathways, with a focus on MAVS signalling. Cells knocked-down cellular factors of interest, made with CRISPr/Cas technology, will be used to further analyse the interaction and the effect on viral replication and immune-and metabolic profiles of infected cells.
In collaboration with Prof. A. Bowie at Trinity College in Dublin, ESR7 will determine the interaction of (specific proteins) of Pneumoviruses with the innate immune, inflammatory and metabolic pathways in more detail. In collaboration with Dr. K. Pardalli at AstraZeneca in Sweden, ESR7 will determine whether pneumovirus inflammasome activation is altered in primary human lung epithelial cells from asthma and/or COPD patients.