Integrative Structural Biology of Cell Division and Energy Homeostasis
Department for Molecular Biology, University of Geneva, Boland lab, Switzerland
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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.
Research interests |
Structural basis of cell division and energy metabolism
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.
Understanding the molecular basis of metabolic protein clusters
Enzymes frequently cluster into large higher-order structures, also termed “metabolons”, to execute sequential, multistep cascade reactions. These macromolecular complexes provide several metabolic advantages, such as substrates channelling between catalytic sites, higher flux rates that are important if the substrate intermediates are instable (i.e. short half-life) and they ensure a high overall catalytic efficiency.
We are using state-of-the-art microscopy methods, such as single particle analysis (SPA), correlative light and electron microscopy (CLEM) combined with FIB-SEM and time-resolved electron microscopy (TREM) to characterise the structure & architecture of such large complex assemblies. We will visualise conformational changes upon substrate binding and determine the underlying kinetics using classical biochemical and biophysical methods. The figure on the right shows the overall architecture of one of our target complexes (negative stain microscopy; top) and the spraying device that will be used to conduct TREM studies (bottom).
Our negative stain reconstruction of a metabolon
Spraying device to perform TrEM experiments
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.
Schematic drawing of cytokine receptor embedded in a lipid bilayer
Structural basis of cell cycle regulation
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
News & Views (NSMB)
Andreas Boland, PhD
+41 22 379 61 27
Marie Skłodowska-Curie Alumni, EMBO Alumni
+41 22 379 34 90
- The PhD retreat has been postponed to 9th to 11th of September, 2020
- Andreas Boland became Program co-director of the Molecular Biosciences program
- Lina Poulain joined as PhD candidate the lab. Welcome Lina!
Structure of the DOCK2-ELMO1 Complex Provides Insights Into Regulation of the Auto-Inhibited State
Chang L, Yang J, Jo CH, Boland A, Zhang Z, McLaughlin SH, Abu-Thuraia A, Killoran RC, Smith MJ, Côté J-F, Barford D.
Nature Communications. 2020 July 10;11(1):3464.
A tri-ionic anchor mechanism drives Ube2N-specific recruitment and K63-chain ubiquitination in TRIM ligases.
Kiss L, Zeng J, Dickson CF, Mallery DL, Yang JC, McLaughlin SH, Boland A, Neuhaus D, James LC.
Nature Communications. 2019 October 3;10(1):4502.
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.
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
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
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
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,
Mol Cell. 2014, Jun 5;54(5):737-50, *equal contributions
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
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
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
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
Crystal structure and ligand binding of the MID domain of a eukaryotic Argonaute protein.
Boland A, Tritschler F, Heimstädt S, Izaurralde E, Weichenrieder O.
* equal contribution
# corresponding author
bold Boland group member
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.
- EM specialist
- Managing Director
FEI Talos Arctica
FEI Tecnai G2 Sphera
Funding - Special thanks to all our current funding bodies
Department of Molecular Biology, Sciences III
30 Quai E. Ansermet
1211 Geneva, Switzerland
Lab: (858) 784-8761
Fax: (858) 784-9985
last modified July 2020