Cv_20130912

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. Structure 21: 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. Cell 25:751-764
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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