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Cambridge Immunology Network

 

Research

The overarching goal of my research program is to gain a mechanistic understanding at the molecular level of how important pathogens interact with their host cells during infection. We seek to understand three major questions: (1) How do spherical enveloped viruses assemble and recognize host cells? (2) How do enveloped viruses deliver their genome into the cytoplasm? (3) How are innate immune responses to microbial nucleic acids generated, amplified and regulated? We employ a diverse set of complementary biophysical approaches including X-ray crystallography, electron microscopy, solution biophysics, fluorescence microscopy and cell biological approaches to understand the mechanisms that underlie these processes in molecular-level detail. Each of our projects has important potential applications in global health.

Recent work in the laboratory has focused on the roles of envelope glycoproteins in the assembly and cell-entry mechanisms of viruses from the flavivirus, bunyavirus and pestivirus families. We also study how nucleic acids derived from these viruses are recognized by the innate immune receptors MDA5 and TLR9, in the cytoplasm and in endocytic compartments, respectively.

Publications

Key publications: 

Adel Nour & Yorgo Modis (2014). Endosomal vesicles as vehicles for viral genomes.Trends Cell Biol., 24, 449-454.

Yorgo Modis (2014). Relating structure to evolution in class II viral membrane fusion proteins. Curr. Op. Virol., 5, 34-41.

Adel M. Nour, Yue Li, Joseph Wolenski & Yorgo Modis (2013). Viral membrane fusion and nucleocapsid delivery into the cytoplasm are distinct events in some flaviviruses.PLOS Pathog., 9, e1003585.

Yue Li, Jimin Wang, Ryuta Kanai & Yorgo Modis (2013). Crystal structure of glycoprotein E2 from bovine viral diarrhea virus. Proc. Natl. Acad. Sci. U.S.A., 110, 6805-10.

Moshe Dessau & Yorgo Modis (2013). Crystal structure of glycoprotein C from Rift Valley fever virus. Proc. Natl. Acad. Sci. U.S.A., 1101696-1701.

Moshe Dessau, Daniel Goldhill, Robert C. McBride, Paul E. Turner & Yorgo Modis(2012). Selective pressure causes an RNA virus to trade reproductive fitness for increased structural and thermal stability of a viral enzyme. PLoS Genet., 8, e1003102.

Ian C. Berke, Xiong Yu, Yorgo Modis & Edward H. Egelman (2012). MDA5 assembles into a polar helical filament on double-stranded RNA. Proc. Natl. Acad. Sci. U.S.A., 109, 18437-41.

Ian C. Berke & Yorgo Modis (2012). MDA5 cooperatively forms dimers and ATP-sensitive filaments upon binding double-stranded RNA. EMBO J., 31, 1714-26.

Yue Li, Ian C. Berke & Yorgo Modis (2012). DNA binding to proteolytically activated TLR9 is sequence-independent and enhanced by DNA curvature. EMBO J. 31, 919-31.

Other publications: 

For a complete list of publications, see: http://www.ncbi.nlm.nih.gov/pubmed/?term=modis%20y

Professor Yorgo  Modis
Takes PhD students
Available for consultancy

Affiliations

Classifications: 
Person keywords: 
TLR
evolution
x-ray crystallography
helminths
molecular biology
electron microscopy
SNAREs
host-parasite interactions
innate immunity
virion assembly
cell culture
host-pathogen interaction
enzyme
C. elegans
structural biology
confocal microscopy
virology
signalling
Toll-like receptors
CARD