Nobel Prize for Synbio Advisor – University of Copenhagen

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11 October 2012

Nobel Prize for Synbio Advisor

 
Member of the external Scientific Advisory Board of Center for Synthetic Biology Professor Brian K. Kobilka of Stanford University has been honoured with the 2012 Nobel Prize in chemistry for describing our cells' sensory gatekeepers. 

Professor Kobilka receives the award alongside Professor Robert J. Lefkowitz of Duke University for the discovery of the G-Protein Coupled Receptors (GPCRs). Since their discovery, researchers have found these proteins on the cell surfaces of virtually all types of eukaryotic cells, including nearly a thousand variants in cells of the human body. The great diversity among the GPCRs in the human body allow different types of cells to react differently to the same external stimuli, e.g. a specific hormone or neurotransmitter. 

Several of the neurobiologists that participate in the Center for Synthetic Biology have collaborated with Professor Kobilka. Member of the Center's steering group, Professor Ulrik Gether has a tight collaboration with the Nobel Laureate with whom he has published numerous joint papers since 1995 (see a joint list of publications below). Claus J. Løland from the same research laboratory has also published jointly with Professor Kobilka.

When the UNIK grant was awarded to establish Center for Synthetic Biology, three Associate Professor positions were advertised internationally and filled by young promising researchers. Within the neurobiology area headed by Professor Gether, the position was assigned to Søren G.F. Rasmussen. Because of his ongoing successful work in Brian Kobilka's lab on the crystal structures and conformational changes of adrenergic receptors, the leadership of the UNIK Center for Synthetic Biology fully accepted and supported that Søren stayed in Brian Kobilka's lab for an additional two years to complete his magnificent work. Søren G.F. Rasmussen's research efforts at Stanford resulted in several seminal papers including six joint Nature papers (three with him as first author, one with shared first authorship), one Nature review and two Nature Methods papers as well as two papers published in Science. 

 

The full list of joint publications between Brian Kobilka, Søren G.F. Rasmussen, Claus J. Løland and Ulrik Gether is listed below.

Chae, P.S., Rasmussen, S.G.F.,  Rana, R.R., Gotfryd, K., Kruse, A.C., Nurva, S., Gether, U., Guan, L., Loland, C.J., Byrne, B., Kobilka, B. and Gellman, S.H. A New Class of Amphiphiles Bearing Rigid Hydrophobic Groups for Solubilization and Stabilization of Membrane Proteins. Chem. Eur. J. (2012) I.F. 5.476

Rasmussen, S.G.F., DeVree, B.T., Zou, Y., Kruse, A.C., Chung, K.Y., Kobilka, T.S., Thian, F.S., Chae, P.S., Pardon, E. Calinski, D., Mathiesen, J.M., Shah, S.T.A., Lyons, J.A., Caffrey, M., Gellman, S.H., Steyaert, J., Skiniotis, G., Weis, W.I., Sunahara, R.K. & Kobilka, B.K., Crystal structure of the β2 adrenergic receptor–Gs protein complex. Nature 477: 549-555 (2011) I.F. 36.104

Chung, K.Y, Rasmussen, S.G.F., Liu, T., Li, S., DeVree, B.T., Chae, P.S., Calinski, D., Kobilka, B.K., Woods, V.L., Sunahara, R.K. Conformational changes in the G protein Gs induced by the β2 adrenergic receptor. Nature 477: 611-615 (2011) I.F. 36.104

Rosenbaum, D.M., Zhang, C., Lyons, J., Holl, R., Aragao, D., Arlow, D.H., Rasmussen, S.G.F., Choi, H.J., DeVree, B.T., Sunahara, R.K., Chae, P.S., Gellman, S.H., Dror, R.O., Shaw, D.E., Weis, W.I., Caffrey, M., Gmeiner, P. and Kobilka, B.K. Structure and Function of an Irreversible Agonist-beta2 Adrenoceptor Complex. Nature 469: 236-240 (2011) I.F. 36.104

Westfield, G., Rasmussen, S.G.F., Su, M., Dutta, S., DeVree, B.T., Chung, K.Y., Calinski, D., Velez-Ruiz, G., Oleskie, A., Pardon, E., Chae, P.S., Liu, T., Li., S., Woods, V.L., Steyeart, J., Kobilka, B.K., Sunahara, R.K. and Skiniotis G. Structural Flexibility of the GalphaS alpha-Helical Domain in the beta2-Adrenoceptor Gs Complex. Proc. Natl. Acad. Sci. USA. 108: 16086-91 (2011) I.F. 9.771

Rasmussen, S.G.F., Choi, H.J., Fung, J.J., Pardon, E., Casarosa, P., Chae, P.S., DeVree, B.T., Rosenbaum, D.M., Thian, F.S., Kobilka, T.S., Schnapp, A., Konetzki, I., Sunahara, R.K., Gellman, S.H., Pautsch, A., Steyaert, J., Weis, W.I., Kobilka, B.K., Structure of a nanobody-stabilized active state of the β2 adrenoceptorNature 469: 175-180 (2011) I.F. 36.104

Bokoch, M.P., Zou, Y., Rasmussen, S.G.F., Liu, C.W., Nygaard, R.,  Rosenbaum, D.M., Fung, J.J., Choi, H.J., Thian, F.S., Kobilka, T.S., Puglisi, J.D., Weis, W.I., Pardo, L., Prossor, R.S., Mueller, L., and Kobilka, B.K., Ligand-Specific Regulation of the Extracellular Surface of a G protein Coupled Receptor. Nature 463: 108-112 (2010) I.F. 36.104

Chae, P.S., Rasmussen, S.G.F., Rana, R., Gotfryd, K., Chandra, R., Goren, M.A., Kruse, A.C., Nurva, S., Loland, C.J., Pierre, Y., Drew, D., Popot, J.L., Picot, D., Fox, B.G., Guan, L., Gether, U., Byrne, B., Kobilka, B. and Gellman, S.H., Maltose-Neopentyl Glycol (MNG) Amphiphiles for Solubilization, Stabilization and Crystallization of Membrane Proteins. Nature Methods  7:1003-8 (2010) I.F. 20.721

Chae, P. S.,  Gotfryd, K., Pacyna, J., Miercke, L.J., Rasmussen, S.G., Robbins, R.A., Rana, R.R., Loland, S.J., Kobilka, B., Stroud, R., Byrne, B., Gether, U., and Gellman, S.H.: Tandem facial amphiphiles for membrane protein stabilization. J Am Chem Soc. 132: 16750-16752 (2010) I.F. 9.023

Rosenbaum, D.M., Rasmussen, S.G.F. & Kobilka, B.K., The Structure and function of G-protein-coupled receptors. Nature 459: 356-363, REVIEW (2009),  I.F. 36.104

Yao, Y.J., Whorton, M.R., Vélez-Ruiz, G., Rasmussen, S.G.F., DeVree, B.T., Deupi, X., Sunahara, R.K. and Kobilka, B.K., The Effect of Ligand Efficacy on the Formation and Stability of a GPCR-G Protein Complex.  Proc. Natl. Acad. Sci. USA. 106: 9501-9506 (2009) I.F. 9.771

Richter, W., Day, P., Agrawal, R., Bruss, M.D., Granier, S., Wang, Y.L., Rasmussen, S.G.F., Horner, K., Wang, P., Lei, T., Patterson, A.J., Kobilka, B.K., Conti, M., Signaling from ß1-and ß2-adrenergic receptors is defined by differential interactions with PDE4. The EMBO Journal 27: 384-393 (2008) 

Day, P.W., Rasmussen, S.G.F., Parnot, C., Fung, J.J., Masood, A., Kobilka, T.S., Yao, X.-J., Choi, H.-J., Weis, W. I.,  Rohrer, D. K. & Kobilka, B. K, A monoclonal antibody for G protein–coupled receptor crystallography. Nature Methods 4: 927-929 (2007) I.F. 20.721

Rasmussen, S.G.F, Choi, H.J., Rosenbaum, D.M., Kobilka, T.S., Thian, F.S., Edwards, P.C., Burghammer, M., Ratnala, V.R.P., Sanishvili, R., Fischetti, R.F., Schertler, G.F.X., Weis, W.I., Kobilka, B.K., Crystal structure of the human β2 adrenergic G-protein-coupled receptorNature 450: 383-387 (2007), I.F. 36.104

Cherezov, V., Rosenbaum, D.M., Hanson, M.A., Rasmussen, S.G.F., Thian, F.S., Kobilka, T.S., Choi, H.J., Kuhn, P., Weis, W.I., Kobilka, B.K., Stevens, R.C., High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science. Nov 23;318(5854):1258-65 (2007), I.F. 31.201

Rosenbaum, D.M., Cherezov, V., Hanson, M.A., Rasmussen, S.G.F., Thian, F.S., Kobilka, T.S., Choi, H.J., Yao, X.J., Weis, W.I., Stevens, R.C., Kobilka, B.K., GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function. Science. Nov 23;318(5854):1266-73 (2007), I.F. 31.201

Whorton, M.R., Bokoch, M.P., Rasmussen, S.G.F., Huang, B., Zare, R.N., Kobilka, B.K., Sunahara, R.K., A monomeric G protein-coupled receptor isolated in a high-density lipoprotein particle efficiently activates its G protein. Proc Natl Acad Sci U S A. 1;104(18):7682-7 (2007)


Kobilka, B.K. & Gether, U.,
Use of fluorescence spectroscopy to study conformational changes in the beta 2-adrenoceptor. Methods Enzymol. 343: 170-82 (2002)

Seifert, R., Wenzel-Seifert, K., Gether, U., Kobilka, B.K., Functional differences between full and partial agonists: evidence for ligand-specific receptor conformations. J Pharmacol Exp Ther. 297(3): 1218-26. (2001)

Ghanouni, P., Schambye, H., Seifert, R., Lee, T.W., Rasmussen, S.G.F., Gether, U., Kobilka, B.K., The effect of pH on beta(2) adrenoceptor function. Evidence for protonation-dependent activation. J Biol Chem. 275 (5) :3121-7. (2000)

Seifert, R., Gether, U., Wenzel-Seifert, K., Kobilka, B.K., Effects of guanine, inosine, and xanthine nucleotides on beta(2)-adrenergic receptor/G(s) interactions: evidence for multiple receptor conformations., Mol Pharmacol., Aug;56(2):348-58 (1999)

Seifert, R., Wenzel-Seifert, K., Gether, U., Lam, V.T., Kobilka, B.K., Examining the efficiency of receptor/G-protein coupling with a cleavable beta2-adrenoceptor-gsalpha fusion protein., Eur J Biochem., Mar;260(3):661-6 (1999)

Kobilka, B.K., Gether, U., Seifert, R., Lin, S., Ghanouni, P., Characterization of ligand-induced conformational states in the beta 2 adrenergic receptor. J Recept Signal Transduct Res.  Jan-Jul;19(1-4):293-300 (1999)

Gether, U., Kobilka, B.K., G protein-coupled receptors. II. Mechanism of agonist activation. J Biol Chem. Jul 17;273(29):17979-82. Review. (1998)

Seifert, R., Wenzel-Seifert, K., Lee, T.W., Gether, U., Sanders-Bush, E., Kobilka, B.K., Different effects of Gsalpha splice variants on beta2-adrenoreceptor-mediated signaling. The Beta2-adrenoreceptor coupled to the long splice variant of Gsalpha has properties of a constitutively active receptor. J Biol Chem. May 1;273(18):5109-16 (1998)

Kobilka, B., Gether, U., Seifert, R., Lin, S., Ghanouni, P., Examination of ligand-induced conformational changes in the beta2 adrenergic receptor. Life Sci. ;62(17-18):1509-12. Review (1998)

Seifert, R., Wenzel-Seifert, K., Lee, T.W., Gether, U., Sanders-Bush, E., Kobilka, B.K., Different effects of Gsalpha splice variants on beta2-adrenoreceptor-mediated signaling. The beta2-adrenoreceptor coupled to the long splice variant of Gsalpha has properties of a constitutively active receptor. J Biol Chem. 1998 Feb 27;273(9):5109-16. Corrected and republished in: J Biol Chem. May 1;273(18):5109-16 (1998)

Gether, U., Lin, S., Ghanouni, P., Ballesteros, J.A., Weinstein, H., Kobilka, B.K., Agonists induce conformational changes in transmembrane domains III and VI of the beta2 adrenoceptor. EMBO J.  Nov 17;16(22):6737-47. (1997)

Kobilka, B.K., Gether, U., Examination of ligand-induced conformational changes in the beta 2-adrenergic receptor by fluorescence spectroscopy, Adv Pharmacol. 42:470-3. (1997)

Gether, U., Ballesteros, J.A., Seifert, R., Sanders-Bush, E., Weinstein, H., Kobilka, B.K., Structural instability of a constitutively active G protein-coupled receptor. Agonist-independent activation due to conformational flexibility. J Biol Chem.  Jan 31;272(5):2587-90. (1997)

Lin, S., Gether, U., Kobilka, B.K., Ligand stabilization of the beta 2 adrenergic receptor: effect of DTT on receptor conformation monitored by circular dichroism and fluorescence spectroscopy. Biochemistry. Nov 19;35(46):14445-51. (1996)

Gether, U., Lin, S., Kobilka, B.K., Fluorescent labeling of purified beta 2 adrenergic receptor. Evidence for ligand-specific conformational changes. J Biol Chem.  Nov 24;270(47):28268-75. (1995)

Homepage of Professor Brian Kobilka's Lab: http://med.stanford.edu/kobilkalab/

Read more about this year's Nobel laureates: http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2012/#

Read more about Ulrik Gether's lab here: 
http://inf.ku.dk/english/research/labs/neuropharm/

Read more about Claus J. Løland's work: 
http://synbio.ku.dk/research/researcher_profiles/claus_loeland/

Read more about Søren Gøgsig Faarup Rasmussen's work:
http://synbio.ku.dk/research/researcher_profiles/soeren_rasmussen/

Watch a video interview with Professor Kobilka and read an article on the two Nobel chemistry laureates: http://www.guardian.co.uk/science/2012/oct/10/nobel-prize-chemistry-receptors-fight-flight

Homepage of The Lefkowitz Lab: http://www.lefkolab.org/