Ikerbasque Research Associate
0000-0001-7807-7049Sean Connell is a Ikerbasque Research Fellow and has been working in the Structural Biology Unit of the CIC bioGUNE since January 2013. His research interests focuses on understanding, at a biochemical and structural level, the molecular details of chemical reactions driving macromolecular machines. He has expertise in the preparation of macromolecular complexes for structural studies, functional characterization of complexes by biophysical means and the structural investigation of macromolecular complexes by cryo-EM.
Dr. Connell graduated from University of Alberta (Canada) in 1997 with a B.Sc. in biochemistry. With funding by an Alberta Heritage Foundation for Medical Research Studentship he earned his Ph.D. in Medical Microbiology in 2003 from the University of Alberta (Canada) and was awarded the Cangene Gold Award from the Canadian Society for Microbiologists for his thesis on the tetracycline resistance protein Tet(O). From 2003-2006, and with the support of an Alexander von Humboldt Research Fellowship, he completed his first post-doc at the Universitätsklinikum Charite (Berlin, Germany) where under the supervision of Prof. Spahn he began using cryo-electron microscopy to characterize complexes of the translational machinery. From 2007-2012 he worked as an independent researcher at the Goethe-Universität (Frankfurt, Germany) and studied macromolecular machines like the ribosome and fatty acid sythetase using cryo-electron microscopy. Currently as a Principle Investigator in the CIC bioGUNE (2013-present) he is studying the role of GTPases in coordinating molecular machines, anti-infectives that target the initiation phase of protein synthesis and the structure of the polyketide synthase.
Latest Publications
2017
2016
2015
2013
Amino acids are assembled into proteins following the genetic instructions encoded in the mRNA in a process called translation. This is primarily governed by a large macromolecular machine called the ribosome. Research in the Fucini and Connell labs focuses on understanding, at a biochemical and structural level, the molecular details of processes that regulate the ribosome at several levels including:
1) Inhibition of core ribosomal activities by antibiotics. Medically relevant antibiotics target the ribosome and inhibit its core functions to exert their anti-microbial activities. We aim to understand how these antibiotics interact with and inhibit the ribosome to improve existing drugs or develop novel antibiotics.
2) Regulation of core activities like initiation, elongation and termination by native protein factors. During protein synthesis the ribosome has several functional activates which are coordinated by specific protein factors. We aim to understand how these factors work together with the ribosome.
3) Ribosome Biosynthesis: Assembling a ribosome requires orchestrating the structural integration of more than 55 ribosomal proteins and three nucleic acid strands in Escherichia coli. This assembly process is facilitated by ribosome assembly factors and we aim to understand how these factors guide the maturation of the ribosome.
4) Co-translational folding and protein sorting. The nascent protein is synthesized in the core of the ribosome and passes through a 100Å long conduit to emerge outside the ribosome. This passage is a highly dynamic and 'personalized' event, where the ribosome and the protein chain communicate to regulate the translation and compartmentalization of the nascent protein. We aim to understand the details of this communication.
Accordingly, the groups have expertise in the preparation and structural characterization of ribosomal complexes. To provide a complete structural understanding of ribosomal functions we employ complementary structural biology methods like X-ray crystallography, NMR (Fucini Lab) and cryo-EM (Connell Lab).
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Principal Investigator
Paola Fucini
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Borja Ochoa de Eribe
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Xu Han
Members
Latest Publications
Backbone and sidechain NMR assignments for the ribosome maturation factor RbfA fromEscherichia coli
Schedlbauer, A;Iturrioz, I;Ochoa-Lizarralde, B;Capuni, R;Han, X;de Astigarraga, E;Diercks, T;Fucini, P;Connell, SR
BIOMOLECULAR NMR ASSIGNMENTS
2020-07-15
Backbone and sidechain NMR assignments for the ribosome maturation factor RimP fromEscherichia coli
Schedlbauer, A;Ochoa-Lizarralde, B;Iturrioz, I;Capuni, R;Diercks, T;de Astigarraga, E;Fucini, P;Connell, SR
BIOMOLECULAR NMR ASSIGNMENTS
2020-04-17
Draft Genome Sequence of Streptomyces sp. Strain AM-2504, Identified by 16S rRNA Comparative Analysis as a Streptomyces kasugaensis Strain
Napolioni, V;Cimarelli, L;Miano, A;La Teana, A;Capuni, R;Giuliodori, AM;Fabbretti, A;Spurio, R
MICROBIOLOGY RESOURCE ANNOUNCEMENTS
2019-09-01
Characterization of the Self-Resistance Mechanism to Dityromycin in the Streptomyces Producer Strain
Fabbretti, A;Capuni, R;Giuliodori, AM;Cimarelli, L;Miano, A;Napolioni, V;La Teana, A;Spurio, R
MSPHERE
2019-09-01
Binding of the protein ICln to alpha-integrin contributes to the activation of IClswell current
Schedlbauer, A;Tammaz, G;Rodighiero, S;Civello, DA;Tamplenizza, M;Ledolter, K;Nofziger, C;Patsch, W;Konrat, R;Paulmichl, M;Dossena, S
SCIENTIFIC REPORTS
2019-08-21
RsgA couples the maturation state of the 30S ribosomal decoding center to activation of its GTPase pocket
Lopez-Alonso, JP(Lopez-Alonso, Jorge Pedro);Kaminishi, T(Kaminishi, Tatsuya);Kikuchi, T(Kikuchi, Takeshi);Hirata, Y(Hirata, Yuya);Iturrioz, I(Iturrioz, Idoia);Dhimole, N(Dhimole, Neha);Schedlbauer, ...
Nucleic acids research
2017-06-20
Structure of a 30S pre-initiation complex stalled by GE81112 reveals structural parallels in bacterial and eukaryotic protein synthesis initiation pathways
Lopez-Alonso, JP(Lopez-Alonso, Jorge P.);Fabbretti, A(Fabbretti, Attilio);Kaminishi, T(Kaminishi, Tatsuya);Iturrioz, I(Iturrioz, Idoia);Brandi, L(Brandi, Letizia);Gil-Carton, D(Gil-Carton, David);Gualerzi, ...
Nucleic acids research
2017-02-28
The Novel Aminomethylcycline Omadacycline Has High Specificity for the Primary Tetracycline-Binding Site on the Bacterial Ribosome
Heidrich, CG(Heidrich, Corina G.);Mitova, S(Mitova, Sanya);Schedlbauer, A(Schedlbauer, Andreas);Connell, SR(Connell, Sean R.);Fucini, P(Fucini, Paola);Steenbergen, JN(Steenbergen, Judith N.);Berens, ...
Antibiotics (Basel, Switzerland)
2016-12-01
Crystallographic characterization of the ribosomal binding site and molecular mechanism of action of Hygromycin A
Kaminishi, T(Kaminishi, Tatsuya);Schedlbauer, A(Schedlbauer, Andreas);Fabbretti, A(Fabbretti, Attilio);Brandi, L(Brandi, Letizia);Ochoa-Lizarralde, B(Ochoa-Lizarralde, Borja);He, CG(He, Cheng-Guang);Milon, ...
Nucleic acids research
2015-11-16
Structural Characterization of an Alternative Mode of Tigecycline Binding to the Bacterial Ribosome
Schedlbauer, A(Schedlbauer, Andreas);Kaminishi, T(Kaminishi, Tatsuya);Ochoa-Lizarralde, B(Ochoa-Lizarralde, Borja);Dhimole, N(Dhimole, Neha);Zhou, S(Zhou, Shu);Lopez-Alonso, JP(Lopez-Alonso, ...
Antimicrobial agents and chemotherapy
2015-05-01
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Borja Ochoa de Eribe
Members
Latest Publications
Backbone and sidechain NMR assignments for the ribosome maturation factor RbfA fromEscherichia coli
Schedlbauer, A;Iturrioz, I;Ochoa-Lizarralde, B;Capuni, R;Han, X;de Astigarraga, E;Diercks, T;Fucini, P;Connell, SR
BIOMOLECULAR NMR ASSIGNMENTS
2020-07-15
Backbone and sidechain NMR assignments for the ribosome maturation factor RimP fromEscherichia coli
Schedlbauer, A;Ochoa-Lizarralde, B;Iturrioz, I;Capuni, R;Diercks, T;de Astigarraga, E;Fucini, P;Connell, SR
BIOMOLECULAR NMR ASSIGNMENTS
2020-04-17
Draft Genome Sequence of Streptomyces sp. Strain AM-2504, Identified by 16S rRNA Comparative Analysis as a Streptomyces kasugaensis Strain
Napolioni, V;Cimarelli, L;Miano, A;La Teana, A;Capuni, R;Giuliodori, AM;Fabbretti, A;Spurio, R
MICROBIOLOGY RESOURCE ANNOUNCEMENTS
2019-09-01
Characterization of the Self-Resistance Mechanism to Dityromycin in the Streptomyces Producer Strain
Fabbretti, A;Capuni, R;Giuliodori, AM;Cimarelli, L;Miano, A;Napolioni, V;La Teana, A;Spurio, R
MSPHERE
2019-09-01
Binding of the protein ICln to alpha-integrin contributes to the activation of IClswell current
Schedlbauer, A;Tammaz, G;Rodighiero, S;Civello, DA;Tamplenizza, M;Ledolter, K;Nofziger, C;Patsch, W;Konrat, R;Paulmichl, M;Dossena, S
SCIENTIFIC REPORTS
2019-08-21
RsgA couples the maturation state of the 30S ribosomal decoding center to activation of its GTPase pocket
Lopez-Alonso, JP(Lopez-Alonso, Jorge Pedro);Kaminishi, T(Kaminishi, Tatsuya);Kikuchi, T(Kikuchi, Takeshi);Hirata, Y(Hirata, Yuya);Iturrioz, I(Iturrioz, Idoia);Dhimole, N(Dhimole, Neha);Schedlbauer, ...
Nucleic acids research
2017-06-20
Structure of a 30S pre-initiation complex stalled by GE81112 reveals structural parallels in bacterial and eukaryotic protein synthesis initiation pathways
Lopez-Alonso, JP(Lopez-Alonso, Jorge P.);Fabbretti, A(Fabbretti, Attilio);Kaminishi, T(Kaminishi, Tatsuya);Iturrioz, I(Iturrioz, Idoia);Brandi, L(Brandi, Letizia);Gil-Carton, D(Gil-Carton, David);Gualerzi, ...
Nucleic acids research
2017-02-28
The Novel Aminomethylcycline Omadacycline Has High Specificity for the Primary Tetracycline-Binding Site on the Bacterial Ribosome
Heidrich, CG(Heidrich, Corina G.);Mitova, S(Mitova, Sanya);Schedlbauer, A(Schedlbauer, Andreas);Connell, SR(Connell, Sean R.);Fucini, P(Fucini, Paola);Steenbergen, JN(Steenbergen, Judith N.);Berens, ...
Antibiotics (Basel, Switzerland)
2016-12-01
Crystallographic characterization of the ribosomal binding site and molecular mechanism of action of Hygromycin A
Kaminishi, T(Kaminishi, Tatsuya);Schedlbauer, A(Schedlbauer, Andreas);Fabbretti, A(Fabbretti, Attilio);Brandi, L(Brandi, Letizia);Ochoa-Lizarralde, B(Ochoa-Lizarralde, Borja);He, CG(He, Cheng-Guang);Milon, ...
Nucleic acids research
2015-11-16
Structural Characterization of an Alternative Mode of Tigecycline Binding to the Bacterial Ribosome
Schedlbauer, A(Schedlbauer, Andreas);Kaminishi, T(Kaminishi, Tatsuya);Ochoa-Lizarralde, B(Ochoa-Lizarralde, Borja);Dhimole, N(Dhimole, Neha);Zhou, S(Zhou, Shu);Lopez-Alonso, JP(Lopez-Alonso, ...
Antimicrobial agents and chemotherapy
2015-05-01