Faculty
Robert A. Lamb
Professor
Molecular Biosciences
PhD, ScD, Cambridge
Email: ralamb@northwestern.edu
Phone: (847) 491-5433
Fax: (847) 491-2467
Room: Cook Rm 3141
Research Interests
Viral Glycoproteins, Ion Channels, and RNA-Binding Proteins
Our laboratory is investigating the molecular structure and the mechanism of replication of two enveloped RNA viruses: influenza virus and the paramyxovirus SV5. Both viruses cause diseases in humans and animals, with important biological and socioeconomic consequences.
The influenza viruses and the paramyxovirus SV5 encode seven integral membrane proteinsHA, NA, HN, F, M2, NB, and SHthat exhibit very different membrane topologies and range in size from 566 to 44 amino acids. We are particularly interested in the method of translocation of these proteins across the membrane of the endoplasmic reticulum, the role of glycosylation, and aspects of correct tertiary folding and oligomerization. These processes are a prerequisite for transport along the exocytic pathway; we are identifying cellular chaperone proteins that assist them. Analyzing the functions of these glycoproteins forms another area of interest. One project concerns the mechanism by which the F proteins cause viral-cell and cell-cell fusion. The second project entails the study of the HN glycoprotein, including its role in fusion, the signals and pathways regulating its internalization from the cell surface, and subsequent degradation. The M2 and NB proteins are critical in the replication cycle of influenza viruses. We used electrophysiological methods to demonstrate that the M2 protein has an ion-channel activity that is blocked by the antiviral drug amantadine. In collaboration with Professor Lawrence Pinto, we are performing a detailed structure-function analysis of this minimalistic ion channel. The potential ion-channel activity of NB is also under study.
Selected Publications
An amantadine-sensitive chimeric BM2 ion channel of influenza B virus has implications for the mechanism of drug inhibition. Ohigashi Y, Ma C, Jing X, Balannick V, Pinto LH, Lamb RA. Proc Natl Acad Sci U S A. 2009 Oct 19. [Epub ahead of print]
Functional analysis of the transmembrane domain in paramyxovirus F protein-mediated membrane fusion. Bissonnette ML, Donald JE, DeGrado WF, Jardetzky TS, Lamb RA. J Mol Biol. 2009 Feb 13;386(1):14-36. Epub 2008 Dec 24.
The influenza virus M2 protein cytoplasmic tail interacts with the M1 protein and influences virus assembly at the site of virus budding. Chen BJ, Leser GP, Jackson D, Lamb RA. J Virol. 2008 Oct;82(20):10059-70. Epub 2008 Aug 13.
Lamb, R.A. and T.S. Jardetzky. (2007). Structural basis of viral invasion: lessons from paramyxovirus F. Curr. Opin. Struct. Biol. (in press).
Chen, B.J., G.P. Leser, E. Morita and R.A. Lamb. (2007). Influenza virus hemagglutinin and neuraminidase, but not the matrix protein, are required for assembly and budding of plasmid-derived virus-like particles. J. Virol. 81, 7111-7123.
Tompkins, S. M., Y. Lin, G.P. Leser, K.A. Kramer, D.L. Haas, E.W. Howerth, R.K. Durbin, J.E. Durbin, R. Tripp, R.A. Lamb and B. He. (2007). Recombinant parainfluenza virus 5 (PIV5) expressing the influenza A virus hemagglutinin provides immunity in mice to influenza A virus challenge. Virology (in press).
Lamb, R.A., R.G. Paterson and T.S. Jardetzky. (2006). Paramyxovirus membrane fusion: lessons from the F and HN atomic structures. Virology 344, 30-37.
Yin, H.S., R.G. Paterson, X. Wen, R.A. Lamb, and T.S. Jardetzky. (2006). Structure of the parainfluenza virus 5 F protein in its metastable, pre-fusion conformation. Nature 439, 38-44.
Bissonnette, M.L.Z., S.A. Connolly, D.F. Young, R.E. Randall, R.G. Paterson, and R.A. Lamb. (2006). Analysis of the pH requirement for membrane fusion of different isolates of the paramyxovirus parainfluenza virus 5. J. Virol. 80, 3071-3077.
View all publications by Robert A. Lamb listed in the National Library of Medicine (PubMed). Past and current IBiS students in blue