seegerlab

COLLABORATORS

Our lab has a strongly collaborative spirit and we are engaged in many collaborations at the University of Zurich, in Switzerland and across the globe.
Enrica Bordignon
Ruhr University, Bochum
Enrica is our trusted expert of electron paramagnetic resonance (EPR) and we have a shared interested in investigating membrane transporters using structural and biophysical approaches. Our collaboration started more than a decade ago, when Enrica was senior postdoc in the lab of Gunnar Jeschke at the ETH Zurich, and continued as Enrica became professor first at the FU Berlin and currently at the RUB. Constituting an Italian-Swiss dream team, we jointly investigated the ABC exporter TM287/288 and currently use nanobodies and sybodies as spin-labelled probes to interrogate the conformational cycle of ABC transporters in native membranes and in cells.

Joint Papers

2020  FEBS Lett.

From in vitro towards in situ: structure-based investigation of ABC exporters by electron paramagnetic resonance spectroscopy

Authors: Bordignon E, Seeger MA, Galazzo L, Meier G.

2020  Proc Natl Acad Sci U S A

Spin-labeled nanobodies as protein conformational reporters for electron paramagnetic resonance in cellular membranes

Authors: Galazzo L, Meier G, Timachi MH, Hutter CAJ, Seeger MA, Bordignon E.

2019  Nat Commun, 10(1): p. 2260

The extracellular gate shapes the energy profile of an ABC exporter

Authors: C.A.J. Hutter, M.H. Timachi, L.M. Hurlimann, I. Zimmermann, P. Egloff, H. Goddeke, S. Kucher, S. Stefanic, M. Karttunen, L.V. Schafer, E. Bordignon*, and M.A. Seeger*

2018  Epub.

Atomistic Mechanism of Large-Scale Conformational Transition in a Heterodimeric ABC Exporter

Authors: Göddeke H, Timachi MH, Hutter CAJ, Galazzo L, Seeger MA, Karttunen M, Bordignon E, Schäfer LV. J

2017  Elife, 6.

Exploring conformational equilibria of a heterodimeric ABC transporter

Authors: M.H. Timachi#, C.A. Hutter#, M. Hohl, T. Assafa, S. Böhm, A. Mittal, M.A. Seeger*, and E. Bordignon*

2014  Proc Natl Acad Sci U S A, 111(30): p.11025-30

Structural basis for allosteric cross-talk between the asymmetric nucleotide binding sites of a heterodimeric ABC exporter

Authors: M. Hohl, L.M. Hürlimann, S. Böhm, J. Schöppe, M.G. Grütter, E. Bordignon, and M.A. Seeger*

2012  J Biol Chem, 287(24): p. 20395-406.

Asymmetry in the homodimeric ABC transporter MsbA recognized by a DARPin

Authors: A. Mittal, S. Böhm, M.G. Grütter, E. Bordignon*, and M.A. Seeger*
Hubert Hilbi
Institute of Medical Microbiology, University of Zurich, Switzerland
Hubert is the master of Legionella pneumophila, the pathogen causing Legionnaires’ disease. His lab’s interest is to understand the pathogenicity of this unusual intracellular bacterium, which secrets an astonishing number of around 300 effector proteins to outsmart the infected cell. His most famous quote is: “how to kill one bird with many stones”. Over the past six years, we have collaborated on the structural elucidation of effector proteins (foremost RidL) and teamed up to study mycobacterial siderophores. The Hilbi lab supports us when it comes to fluorescence microscopy. Provided the large number of Legionella effectors, there is still loads to do in the years to come!

Joint Papers

2020  Mol Microbiol.

The structure of the Legionella response regulator LqsR reveals amino acids critical for phosphorylation and dimerization

Authors: Hochstrasser R, Hutter CAJ, Arnold FM, Bärlocher K, Seeger MA, Hilbi H.

2020  Cell Microbiol.

Mycobacterium marinum produces distinct mycobactin and carboxymycobactin siderophores to promote growth in broth and phagocytes

Authors: Knobloch P, Koliwer-Brandl H, Arnold FM, Hanna N, Gonda I, Adenau S, Personnic N, Barisch C, Seeger MA, Soldati T, Hilbi H.

2018  Sci Rep, 8.

A uniform cloning platform for mycobacterial genetics and protein production

Authors: F.M. Arnold, M. Hohl, S. Remm, H. Koliwer-Brandl, S. Adenau, S. Chusri, P. Sander, H. Hilbi, and M.A. Seeger*

2017  Nat Commun.

Structural insights into Legionella RidL-Vps29 retromer subunit interaction reveal displacement of the regulator TBC1D5

Authors: Bärlocher K, Hutter CAJ, Swart AL, Steiner B, Welin A, Hohl M, Letourneur F, Seeger MA, Hilbi H.
Eric Geertsma
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
With Eric we share our enthusiasm for membrane transporters, protein engineering and technological innovations. Our collaboration started back in 2009 when Markus and Eric both were working at the Institute of Biochemistry, University of Zurich. The seegerlab was an early adopter of Eric’s glorious FX cloning technology and we jointly came up with the idea to develop synthetic nanobodies libraries to trap membrane transporters in specific conformations. In a patriotic act, we initially called these synthetic nanobodies Swissbodies, and only later they became what they are now known for: sybodies!

Joint Papers

2020  Nat Protoc, 15(5): p. 1707-1741

Generation of synthetic nanobodies against delicate proteins

Authors: I. Zimmermann, P. Egloff, C.A.J. Hutter, B.T. Kuhn, P. Bräuer, S. Newstead, R.J.P. Dawson, E.R. Geertsma*, and M.A. Seeger*

2020  Methods Mol Biol.

Biotinylation of Membrane Proteins for Binder Selections

Authors: Kuhn BT, Zimmermann I, Egloff P, Hürlimann LM, Hutter CAJ, Miscenic C, Dawson RJP, Seeger MA, Geertsma ER.

2018  Elife, 7.

Synthetic single domain antibodies for the conformational trapping of membrane proteins

Authors: I. Zimmermann#, P. Egloff#, C.A. Hutter, F.M. Arnold, P. Stohler, N. Bocquet, M.N. Hug, S. Huber, M. Siegrist, L. Hetemann, J. Gera, S. Gmur, P. Spies, D. Gygax, E.R. Geertsma*, R.J. Dawson*, and M.A. Seeger*

2015  Biochemistry.

A Transporter Motor Taken Apart: Flexibility in the Nucleotide Binding Domains of a Heterodimeric ABC Exporter

Authors: Bukowska MA, Hohl M, Geertsma ER, Hürlimann LM, Grütter MG, Seeger MA.

2015  J Mol Biol.

Bicistronic mRNAs to enhance membrane protein overexpression

Authors: Marino J, Hohl M, Seeger MA, Zerbe O, Geertsma ER.
Simon Newstead
University of Oxford, UK
With Simon we share the fascination for membrane transporter structure and function and he is a master of lipidic cubic phase crystallography. In summer 2017, we engaged in a collaboration to generate sybodies against the KDEL receptor and in record time, the project yielded a beautiful structure published in March 2019. In late 2019, we received a Wellcome collaborative award together with Francis Barr and Phil Biggin (both at University of Oxford) to study receptor mediated trafficking within the early secretory at the structural and cell biology level using sybodies and NestLink.

Joint Papers

2020  Nat Protoc, 15(5): p. 1707-1741

Generation of synthetic nanobodies against delicate proteins

Authors: I. Zimmermann, P. Egloff, C.A.J. Hutter, B.T. Kuhn, P. Bräuer, S. Newstead, R.J.P. Dawson, E.R. Geertsma*, and M.A. Seeger*

2019  Science, 363(6431): p. 1103-1107

Structural basis for pH-dependent retrieval of ER proteins from the Golgi by the KDEL receptor

Authors: P. Bräuer, J.L. Parker, A. Gerondopoulos, I. Zimmermann, M.A. Seeger, F.A. Barr, and S. Newstead
Sebastian Hiller
Sebastian knows the ins and outs of outer membrane proteins and is the master of BamA. With a joint SNF BRIDGE Discovery grant, we have established strong ties to shed light on the mysteries of BamA structure/function using nanobodies and sybodies. We aim to develop novel bioantibiotics targeting BamA of problematic ESKAPE pathogens.

Joint Papers

2019  J Biomol NMR.

Identification of conformation-selective nanobodies against the membrane protein insertase BamA by an integrated structural biology approach

Authors: Kaur H, Hartmann JB, Jakob RP, Zahn M, Zimmermann I, Maier T, Seeger MA, Hiller S.
Peter Sander
Institute of Medical Microbiology, University of Zurich
With Peter, we collaborate on mycobacteria-related projects, in particular investigating resistance and pathogenicity mechanisms of Mycobacterium abscessus.

Joint Papers

2019  Mol Microbiol

Increased drug permeability of a stiffened mycobacterial outer membrane in cells lacking MFS transporter Rv1410 and lipoprotein LprG

Authors: M. Hohl#, S. Remm#, H.A. Eskandarian, M. Dal Molin, F.M. Arnold, L.M. Hürlimann, A. Krügel, G.E. Fantner, P. Sander, and M.A. Seeger*

2018  Sci Rep, 8.

A uniform cloning platform for mycobacterial genetics and protein production

Authors: F.M. Arnold, M. Hohl, S. Remm, H. Koliwer-Brandl, S. Adenau, S. Chusri, P. Sander, H. Hilbi, and M.A. Seeger*
Philippe Plattet
Division of Eperimental Clinical Research, University of Berne
During the Corona year of 2020, we engaged in a collaboration with Phil to rapidly generate sybodies against SARS-CoV-2. Phil brings in the virology expertise into this fruitful collaboration and together with the lab of Dimitrios Fotiadis, we received funding from the SNSF NRP78 program “Covid-19”.

Joint Papers

2020  

Highly potent bispecific sybodies neutralize SARS-CoV-2

Authors: J. D. Walter, C. A. J. Hutter, A. A. Garaeva, M. Scherer, I. Zimmermann, M. Wyss, J. Rheinberger, Y. Ruedin, J. C. Earp, P. Egloff, M. Sorgenfrei, L. M. Hürlimann, I. Gonda, G. Meier, S. Remm, S. Thavarasah, G. Zimmer, D. J. Slotboom, C. Paulino, P. Plattet, M. A. Seeger
Peter Keller
Peter Keller is our innovative diagnostics expert with whom we collaborate in our SNSF NRP 72 project aiming at the generation of nanobodies for rapid diagnostics of blood stream infections caused by gram-negative ESKAPE pathogens.