Robert A. Lamb
John Evans Professor
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 proteins: HA, NA, HN, F, M2, NB, and SH, that 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.
Structure and stabilization of the Hendra virus F glycoprotein in its prefusion form. Wong JJW, Paterson RG, Lamb RA, and Jardetzky TS. PNAS. 2016 January 26;113(4):1056-1061.
Type II integral membrane protein, TM of J paramyxovirus promotes cell-to-cell fusion. Li Z, Hung C, Paterson RG, Michel F, Fuentes S, Place R, Lin Y, Hogan RJ, Lamb RA, and He B. PNAS. 2015 October 6;112(40):12504-12509.
Timing is everything: Fine-tuned molecular machines orchestrate paramyxovirus entry. Bose S, Jardetzky TS, and Lamb RA. Virology. 2015 May;479-480:518-531.
Structure of the paramyxovirus parainfluenza virus 5 nucleoprotein–RNA complex. Alayyoubi M, Leser GP, Kors CA, and Lamb RA. PNAS. 2015 April 7;112(14):E1792-E1799.
On the Stability of Parainfluenza Virus 5 F Proteins. Poor TA, Song AS, Welch BD, Kors CA, Jardetzky TS, and Lamb RA. Journal of Virology. 2015 March;89(6):3438-3441.
Influenza A Virus Uses Intercellular Connections to Spread to Neighboring Cells. Roberts KL, Manicassamy B, and Lamb RA. Journal of Virology. 2015 February;89(3):1537-1549.
Flipping in the Pore: Discovery of Dual Inhibitors That Bind in Different Orientations to the Wild-Type versus the Amantadine-Resistant S31N Mutant of the Influenza A Virus M2 Proton Channel. Wu Y, Canturk B, Jo H, Ma C, Gianti E, Klein ML, Pinto LH, Lamb RA, Florin G, Wang J, and DeGrado WF. Journal of the American Chemical Society. 2014 December 31;136(52):17987-17995.
Probing the Functions of the Paramyxovirus Glycoproteins F and HN with a Panel of Synthetic Antibodies. Welch BD, Paduch M, Leser GP, Bergman Z, Kors CA, Paterson RG, Jardetzky TS, Kossiakoff AA, and Lamb RA. Journal of Virology. 2014 October;88(20):11713-11725.
The Innate Immune Sensor LGP2 Activates Antiviral Signaling by Regulating MDA5-RNA Interaction and Filament Assembly. Bruns AM, Leser GP, Lamb RA, and Horvath CM. Molecular Cell. 2014 September 4;55(5):771-781.
Easily Accessible Polycyclic Amines that Inhibit the Wild-Type and Amantadine-Resistant Mutants of the M2 Channel of Influenza A Virus. Rey-Carrizo M, Barniol-Xicota M, Ma C, Frigolé-Vivas M, Torres E, Naesens L, Llabrés S, Juárez-Jiménez J, Luque FJ, DeGrado WF, Lamb RA, Pinto LH, and Vázquez S. Journal of Medicinal Chemistry. 2014 July 10;57(13):5738-5747.
Probing the paramyxovirus fusion (F) protein-refolding event from pre- to postfusion by oxidative footprinting. Poor TA, Jones LM, Sood A, Leser GP, Plasencia MD, Rempel DL, Jardetzky TS, Woods RJ, Gross ML, and Lamb RA. PNAS. 2014 June 24;111(25):E2596-E2605.
Fusion Activation through Attachment Protein Stalk Domains Indicates a Conserved Core Mechanism of Paramyxovirus Entry into Cells. Bose S, Song AS, Jardetzky TS, and Lamb RA. Journal of Virology. 2014 April;88(8):3925-3941.
Mutations in the Parainfluenza Virus 5 Fusion Protein Reveal Domains Important for Fusion Triggering and Metastability. Bose S, Heath CM, Shah PA, Alayyoubi M, Jardetzky TS, and Lamb RA. Journal of Virology. 2013 December;87(24):13520-13531.
View all publications by Robert A. Lamb listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.