My research interests focus on understanding, at a biochemical and structural level, the mechanisms that drive molecular machines. In particular my aim is to use cryo-EM in
combination with image processing techniques to uncover conformational changes that play functional roles in protein translation (ribosome) and polyketide synthesis (PKS). Principle Investigator, CIC bioGUNE, Bilbao, Spain. 2013-Present
Parque Tecnológico de Vizcaya, Ed. 80048160 Derio
Cryo-EM investigations of ribosomal assembly, regulation of protein synthesis by RACK associated proteins and the the structure/conformational variability in PKS-associated
Post-Doctorial Researcher; Goethe-Universität, Frankfurt, Germany 2007-2012 Structural Studies (X-ray/NMR/cryo-EM) on ribosomal complexes. For combined 12 months period between 2007-2009 I have been on paternity leave. Post-Doctorial Researcher; Universitätsklinikum Charite Berlin, Germany 2003-2006 Structural characterization of translational regulation using cryo-electron microscopy Graduate Student; University of Alberta Edmonton, Canada 1997-2002 Characterization of tetracycline resistance mediated by the ribosomal protection protein Tet(O). My research was carried out in collaboration with Dr. Prof. Knud Nierhaus at the Max-Planck-Institut für Molekulare Genetik and I worked extensively in his lab from 1998-2001.
EducationUniversity of Alberta, Edmonton, Canada, Ph.D., 2003University of Alberta, Edmonton, Canada, B.Sc., 1997
AwardsIkerbasque Research Fellow, 2013-2018Bizkaia:xede Fellowship, 2013
Alexander von Humboldt Research Fellowship, 2004-2005The Canadian Society for Microbiologists Graduate Student Cangene Gold Award, 2003Alberta Heritage Foundation for Medical Research Studentship, 1998-2003Mary Louise Imrie Graduate Student Award, 1998
Publications Zhou S., Schedlbauer A., Connell S.R., and Fucini P. Transient α-helical in the intrinsic disordered C terminal domain of Yeast Oxa1 interacts with ribosome. In Preparation Connell S.R., Kikuchi T., Hirata Y., Hase Y., Goto S., Kurita D., Muto A., Naoe C.,
Takemoto C., Yokoyama S., Zhou S. , Mills D.J., Fucini P., Himeno H. Interaction
of RsgA and the 30S ribosomal subunit revealed by directed hydroxyl radical
probing and single particle cryo-EM. In Preparation
Parque Tecnológico de Vizcaya, Ed. 80048160 Derio
Ciccarelli L., Connell S.R., Enderle M., Mills D.J., Vonck J., and Grininger M. (2013) Structure and conformational variability of the mycobacterium tuberculosis
fatty acid synthase multienzyme complex. Structure21: 1251–1257.
Gelis I., Vitzthum V., Dhimole N., Caporini M.A,. Schedlbauer A., Carnevale D., Connell S.R., Fucini P., and Bodenhausen G. (2013) Solid-state NMR enhanced by dynamic nuclear polarization as a novel tool for ribosome structural biology. J Biomol NMR. 56: 85-93
Ratje A.H., Loerke J., Mikolajka A., Brünner M., Hildebrand P.W., Starosta A.L., Dönhöfer A., Connell S.R., Fucini P., Mielke T., Whitford P.C., Onuchic J.N., Yu Y., Sanbonmatsu K.Y., Hartmann R.K., Penczek P.A., Wilson D.N., and Spahn C.M.T. (2010) Head swivel on the ribosome facilitates translocation via intra-subunit tRNA hybrid sites. Nature 468:713-716
Schuette J.C., Murphy F.V., Kelley A.C., Weir J.R., Giesebrecht J., Connell S.R., Loerke J., Mielke T., Zhang W., Penczek P.A., Ramakrishnan V., Spahn C.M.T. (2009). GTPase activation of elongation factor EF-Tu by the ribosome during decoding. EMBO J. 28:755-765 Connell S.R., Topf M. Qin Y., Wilson D.N., Mielke T., Fucini P., Nierhaus K.H. and Spahn C.M.T. (2008). A new tRNA intermediate revealed on the ribosome during EF4-mediated back-translocation. NSMB 15:910-915
Wilson D.N., Schluenzen F., Harms J.M., Starosta A.L., Connell S.R., and Fucini P. (2008). The oxazolidinone antibiotics perturb the ribosomal peptidyl-transferase center and effect tRNA positioning. PNAS 105:13339-13344
Harms J.M., Wilson D.N., Schluenzen F., Connell S.R., Stachelhaus T., Spahn C.M.T., and Fucini P. (2008). Translational regulation via L11: molecular switches on the ribosome turned on and off by thiostrepton and micrococcin. Mol. Cell 30:26-38 Connell S.R., Takemoto C., Wilson D.N., Wang H., Murayama K., Terada T., Rost M., Schüler M., Giesebrecht J., Dabrowski M., Mielke T., Fucini P., Yokoyama S. and Spahn C.M.T. (2007). Structural Basis for Interaction of the Ribosome with the Switch Regions of GTP-Bound Elongation Factors. Mol. Cell25:751-764
Schüler M., Connell S.R., Lescoute A., Giesebrecht J., Dabrowski M., Schroeer B., Mielke T., Penczek P.A., Westhof E., Spahn C.M.T. (2006) Structure of the ribosome-bound cricket paralysis virus IRES RNA. NSMB 13:1092-1096
Nonaka L., Connell S.R., and Taylor D.E. (2005). 16S rRNA mutations that confer tetracycline resistance in Helicobacter pylori decrease drug binding in Escherichia coli ribosomes. J Bacteriol. 187(11):3708-12
Gibreel A., Tracz D.M., Nonaka L., Ngo T.M., Connell S.R. and Taylor D.E. (2004). Incidence of antibiotic resistance in Campylobacter jejuni isolated in Alberta, Canada, from 1999 to 2002, with special reference to tet(O)-mediated tetracycline resistance. Antimicrob Agents Chemother. 48(9):3442-50.
Christodoulou J., Larsson G., Fucini P., Connell S.R., Pertinhez T.A., Hanson C.L., Redfield C., Nierhaus K.H., Robinson C.V., Schleucher J., Dobson C.M. (2004). Heteronuclear NMR investigations of dynamic regions of intact Escherichia coli ribosomes. Proc Natl Acad Sci 101(30):10949-54.
Gilbert R.J., Fucini P., Connell S., Fuller S.D., Nierhaus K.H., Robinson C.V., Dobson C.M.,
and Stuart D.I. (2004). Three-dimensional structures of translating ribosomes by Cryo-EM.
Mol Cell. 14(1): 57-66. Connell S.R., Tracz D.M., Nierhaus K.H. and Taylor D.E. (2003). Ribosomal protection
proteins and their mechanism of tetracycline-resistance. Antimicrob. Agents Chemother.
47(12): 3675-3681. Connell S.R., Trieber C.A., Einfeldt E., Dinos G.P., Taylor D.E., and Nierhaus K.H. (2003). Mechanism of Tet(O)-mediated tetracycline resistance. Embo J. 22(4): 945-953.
Dinos G.P., Connell S.R., Nierhaus K.H., and Kalpaxis D.L. (2003). Erythromycin, roxithromycin, and clarithromycin: Use of slow-binding kinetics to compare their in vitro interaction with a bacterial ribosomal complex active in peptide bond formation. Mol. Pharm 63(3): 617-623. Connell S.R., Trieber C.A., Stelzl U., Einfeldt E., Taylor D.E., and Nierhaus K.H. (2002). The tetracycline resistance protein, Tet(O), perturbs the conformation of the ribosomal decoding center. Mol Microbiol 45(6): 1463-1472.
Wilson D.N,, Blaha G., Connell S.R., Ivanov P.V., Jenke H., Stelzl U., Teraoka Y., and Nierhaus K.H. (2002). Protein synthesis at atomic resolution: Mechanistics of translation in the light of highly resolved structures for the ribosome. Current Protein and Peptide Science 3: 1-53.
Spahn C.M., Blaha G., Agrawal R.K., Penczek P., Grassucci R.A., Trieber C.A., Connell S.R., Taylor D.E., Nierhaus K.H., and Frank J. (2001). Localization of the ribosomal protection protein Tet(O) on the ribosome and the mechanism of tetracycline resistance. Mol Cell. 7(5): 1037-1045. Connell S., and Nierhaus K.H. (2000). Translational termination not yet at its end. Chembiochem. 1(4): 250-253.
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