Structure of interferon signaling complexes by cryo-electron microscopy

The type I interferons (IFNs) are cytokines pivotal to the host innate immune response, which protects against viral and bacterial infections and cancer. Up to 20 different ligands share the same heterodimeric receptor. Work in our laboratory focuses on investigating structure of the different type I IFNs (including the IFNa family, IFNb and IFNe) and how they engage their receptors to activate signal transduction pathways and thus, the transmission of differential signals. This project involves the use of biochemical techniques for the purification of recombinant forms of the IFNs and their receptors and determination of their structure by cryo-electron microscopy and may include other such biophysical techniques as native gel electrophoresis, mass photometry, site-directed mutagenesis, protein-protein interactions, cross-linking mass spectrometry. Aspects of this ongoing work were published in Nature Immunology (2013) Sep; 14(9):901-7 and the Journal of Biological Chemistry (2017) Mar; PMID: 28289093.