Structural Biology of Cell Signalling and Cell Division
Department for Molecular Biology, University of Geneva, Boland lab, Switzerland

Artwork by Margot Riggi (Margot.Riggi@unige.ch)

News

December 2018:

 

- The lab web page goes online! 

- We welcome applications from pre- and post-doctoral research scientists, who wish to work in the field of Cell Signaling and Cell Division. We leverage Structural Biology methods, and here in particular cryo-electron microscopy (cryo-EM) and X-ray crystallography with complementary Cell Biology methods (proteomics, light-microscopy, fluorescence-based reporter assays, etc.), to elucidate the intricate structure and function relationship of large macro-molecular complexes involved in signal transduction and cell cycle control (see current and past research).

If you wish to receive more information about future projects please contact Andreas Boland (Andreas.Boland@unige.ch) directly.

last update December 2018

Structural Gallery

 

Research interests

In recent years, cryo-electron microscopy has been proven to be an extremely powerful tool to obtain unprecedented high-resolution information of particular challenging protein targets, such as large macro-molecular machines or membrane proteins, many of which seemed inaccessible to structural studies only a few years ago. Technological advances including commercially available direct electron detector (DED) in combination with the development of new computational algorithms have revolutionized the field of cryo-electron microscopy and structural biology in general. Recently published structures of putative pharmaceutical targets have emphasized the potential of cryo-electron microscopy for structure-based drug design.

Separase is an enzyme that is responsible for cleaving the kleisin subunits (Scc1 and Rec8) of the cohesin ring that holds sister chromatids together during mitosis. Once the chromatids are liberated by separase, they segregate towards opposite poles of the cell, ready to form new nuclei in two identical daughter cells. Separase is kept in check by an inhibitory chaperone known as securin, which is intriguingly also believed to have activating properties.  Although discovered almost 20 years ago, it is only recently that the structure of separase bound to securin has been elucidated.

It was discovered that securin forms an extended conformation to interact along the entire length of separase, and inhibits the enzyme through a pseudosubstrate mechanism at the active site. A full understanding of this interaction and nature of cell cycle control could open up new avenues for targeted drug design and will be one research branch that we will be pursuing. 

Cryo-EM structure of a metazoan separase-securin complex at near-atomic resolution.  Boland A et al., NSMB, 2017

Cytokines are small soluble proteins that facilitate communication between cells in the immune and hematopoietic system. In response to external stimuli, they bind to specific cell surface receptors to trigger intracellular signalling cascades that are vital for a broad spectrum of cell functions, including proliferation and differentiation, immune responses and energy metabolism. Consequently, cytokines and their receptors are highly relevant drug targets. To elucidate the structure-function relationship of selected target receptors will be the second main branch of our lab research.

Past research

In animal cells, miRNAs silence the expression of mRNA targets through translational repression and/or deadenylation. Silencing requires the association of miRNAs to an Argonaute protein, which moreover binds to a member of the GW182/TNRC6C protein family. In turn, GW182 proteins interact with the two major cytoplasmic deadenylase complexes, the PAN2-PAN3 complex and the CCR4-NOT complex, to induce deadenylation and hence promote decay of miRNA targets.
Structures of crucial complexes have been solved using X-ray crystallography (see References).

Schematic drawing of cytokine receptor embedded in a lipid bilayer

Structural characterization of eukaryotic mRNA decay factors involved in post-transcriptional gene regulation,
© Andreas Boland, PhD thesis, 2014.

 

Lab philosophy

Welcome to the Boland lab! We are a small, focused and enthusiastic group working at the intersection of Structural Biology, Molecular Biology and Cell Biology. We leverage the latest developments in Structural Biology, and here in particular cryo-electron microscopy (cryo-EM) with complementary biophysical techniques (proteomics, light-microscopy, microfluidics, etc.), to adress complex biological questions in the field of cell cycle regulation and cell signaling.

Andreas Boland, PhD

Associate Professor at the University of Geneva
(Department of Molecular Biology)


        Andreas.Boland@unige.ch

        +41 22 379 61 27
 

Marie Skłodowska-Curie Alumni, EMBO Alumni

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Yvan Pfister
Research assistant


       Yvan.Pfister@unige.ch

       +41 22 379 34 90

 

References

2018

The CryoEM Structure of the Ribosome Maturation Factor Rea1. 

Sosnowski P, Urnavicius L, Boland A, Fagiewicz R, Busselez J, Papai G, Schmidt H.
eLife. 2018 November 21;7 epub.

Europe PMC | doi

2017

The potential of cryo-electron microscopy for structure-based drug design. 

Boland A, Chang L, Barford D.
Essays in Biochemistry. 2017 November;61(5):543-560

Europe PMC | doi

Cryo-EM structure of a metazoan separase-securin complex at near-atomic resolution. 

Boland A#, Martin TG, Zhang Z, Yang J, Bai X-C, Chang L, Scheres S, Barford D.
Nat Struct Mol Biol. 2017 April;24(4):414-418

Europe PMC | doi

2015

Fast native-SAD phasing for routine macromolecular structure determination.

Weinert T, Olieric V, Waltersperger S, Panepucci E, Chen L, Zhang H, Zhou D, Rose J, Ebihara A, Kuramitsu S, Li D, Howe N, Pautsch A, Bargsten K, Prota A, Surana P, Kottur J, Nair D, Basilico F, Cecatiello V, Pasqualato S, 
Boland A, Weichenrieder O, Dekker C, Wang B-C, Steinmetz M, Caffrey M, Wang M.

Nature methods. 2015 Feb;12(2):131-133

Europe PMC doi

2014

A DDX6-CNOT1 complex and W-binding pockets in CNOT9 reveal direct links between
miRNA target recognition and silencing. 

Chen Y*Boland A*, Kuzuoğlu-Öztürk D*, Bawankar P, Chang CT, Loh B, Weichenrieder O,
Izaurralde E.

Mol Cell. 2014, Jun 5;54(5):737-50, *equal contributions 

Europe PMC | doi

2013

Structure and assembly of the NOT module of the CCR4-NOT complex. 
Boland A*, Chen Y*, Raisch T*, Jonas S*, Kuzuoğlu-ÖztürkD, Wohlbold L, Weichenrieder O, Izaurralde E.
Nat Struct Mol Biol. 2013 Nov;20(11):1289-97, *equal contributions 

Europe PMC | doi

Structure of the PAN3 pseudokinase reveals the basis for interactions with the PAN2 deadenylase and the GW182/TNRC6 proteins. 
Christie M*Boland A*, Huntzinger E, Weichenrieder O, Izaurralde E.
Mol Cell. 2013 Aug 8;51(3):360-73,*equal contributions

Europe PMC | doi

2012

A direct interaction between DCP1 and XRN1 couples mRNA decapping to 5' exonucleolytic degradation.

Braun JE, Truffault V, Boland A, Huntzinger E, Chang CT, Haas G, Weichenrieder O, 
Coles M,Izaurralde E.

Nat Struct Mol Biol. 2012 

Europe PMC | doi

2011

Crystal structure of the MID-PIWI lobe of a eukaryotic Argonaute protein.

Boland A, Huntzinger E, Schmidt S, Izaurralde E, Weichenrieder O.
Proc Natl Acad Sci U S A. 2011

Europe PMC | doi

2010

Crystal structure and ligand binding of the MID domain of a eukaryotic Argonaute protein. 
Boland A, Tritschler F, Heimstädt S, Izaurralde E, Weichenrieder O.
EMBO Rep.2010

Europe PMC | doi

* equal contribution
# corresponding author
bold Boland group member

 

Facilities

The University of Geneva offers a vast range of outstanding scientific facilities and support services, all available to members of the lab.
 

Members have acces to the electron microscopy facility which includes a FEI Tecnai™ G2 Sphera for cryo-EM single particle analysis and a JEOL JSM-6510LV scanning electron microscope.
In the near future this facility will be upgraded by two more electron microscopes, including a Talos L120C  (an ideal screening microscope for single particle analysis), as well as a state-of-the-art Talos Arctica microscope equipped with a Falcon III detector enabling high-resolution data collection (see images on the right).

More information can be found on the Bioimaging Center website of the University (http://bioimaging.unige.ch/).

The Bioimaging Center was founded in 2002 by the NCCR Frontiers in Genetics. It is a common platform of the Faculty of Sciences and iGE3. Under the auspices of the iGE3, it is mainly supported by the Section of Biology and the Biochemistry Department. The Center is open to the entire scientific and biomedical community of the Geneva academic landscape.

It is dedicated to providing state-of-the-art equipment and technology for light and electron microscopy. Specialists offer advice and guidance for each step of your imaging project starting from experimental approach to data analysis.

FEI Tecnai G2 Sphera

Talos L120C

FEI Talos Arctica

 

Funding

 

Contact Us

Mailing adress:

Boland laboratories

(andreas.boland@unige.ch)

Department of Molecular Biology, Sciences III

30 Quai E. Ansermet

1211 Geneva, Switzerland

Lab: (858) 784-8761
Fax: (858) 784-9985