IBS - Institut de Biologie Structurale - Grenoble / France

Group members

Da Silva Catarina — 2024-09-04T17:46:39Z

Permanent staff

Irina Gutsche
CNRS Researcher
Ambroise Desfosses
CNRS Researcher

Maria Bacia-Verloop
CNRS Research Engineer

MIAI Chair

Daniel Orozco
MIAI Research Chair

PhD students

Madalena Branco
PhD student UGA/ILL
Co-supervised with Judith Peters from the group ILL/LiPhy

Héloïse Roy
PhD student UGA (Labex GRAL)
Co-supervised with Julien Sourimant, INRAE, Jouy-en-Josas

Postdocs

Catarina S. Silva
Postdoc

Harald Bernhard
Postdoc
Co-supervised with Joanna Timmins from the group I2SR/team GenOM

Brandon Le Bon
Computer Engineer

Laura Belot
Postdoc

Alumni

Moritz Kirchner (PhD student UGA/CEA co-supervised with Jean-Philippe Kleman from the group I2SR/team GenOM, 2023-2026)
Eymeline Pageot (PhD student UGA, concours EDCSV; Labex GRAL PhD OC, 2022-2026)
Lorène Gonnin (Postdoc co-supervised with Linda Sandblad and UCEM, Umeå University, 2023-2025)
Madalen Le Gorrec (Assistant Engineer CNRS, 2020-2025)
Jahnavi Jangala (PhD student UGA/ITN Glytunes, 2021-2025)
Léana Yu (M1 student, 2025)
Aidana Baltabekova (M1 student, 2025)
Lorenzo Gaifas (Labex GRAL PhD student co-supervised with Joanna Timmins from the group I2SR/team GenOM, 2020-2024)
Tamás Földes (postdoc co-supervised with Judith Peters from the group ILL/LiPhy, 2023-2024)
Lorène Gonnin (PhD student co-supervised with Jean-François Eléouët, 2019-2023)
Lindsay McGregor (postdoc, 2021-2022)
Yoan Duhoo (postdoc, 2021-2022)
Karine Huard (Engineer, 2016-2021)
Alister Burt (PhD student, 2017-2021)
Angélique Fraudeau (Engineer, 2015-2020)
Jan Felix (postdoc, 2016-2020)
Matthew Jessop (PhD student, 2016-2020)
Clarissa Liesche (postdoc, 2016-2020)
Megghane Baulard (AI-M2-IE, 2015-2018)
Eaazhisai Kandiah (postdoc, 2015-2017)
Diego Carriel (PhD student, 2013-2017)

Visiting scientists

Krzysztof Raszpla (visiting PhD student, 2026)
Sergio Garcia (visiting postdoc, 2025)
Swasti Rawal (visiting PhD student, 2024)
Venetia Psomiadou (visiting PhD student, 2023)
Suresh Banjara (visiting postdoc, 2023)
Jana Nedvedova (visiting PhD student, 2021-2022)
Jennifer Kefauver (visiting postdoc, 2021-2022)
Ladislav Bumba (visiting Professor, 2018-2019)

2018: Karine, Clarissa, Jan, Irina, Matt, Alister, Angélique and Ambroise (from left to right)

2020: Yoan, Ambroise, Madalen, Lorenzo, Karine, Irina, Elena (a collaborator from Vilnius), Lorène, Lindsay (from left to right)

2024: Ambroise, Moritz, Lorenzo, Eymeline, Madalen, Irina, Jahnavi, Sinan (L3 student), Swasti (visiting PhD student), Catarina, Anaïs (L3 student) (from top to bottom)

2024: Catarina, Brandon, Madalena, Madalen, Eymeline, Tamás, Moritz, Jahnavi, Lorenzo, Irina, Ambroise (from left to right)

2025: Ambroise, Brandon, Lorène, Aidana, Jahnavi, Hari, Eymeline, Tamás, Madalena, Moritz, Laura, Irina, Lorenzo, Catarina, Léana, Madalen, Maria (from left to right)

2026: Ambroise, Krzysztof, Aidana, Héloïse, Laura, Madalena, Moritz, Léa, Brandon, Hari, Catarina, Tamás, Maria, Irina (from left to right)

Methods development

Da Silva Catarina — 2024-08-23T17:55:43Z

Methods development
Lorenzo Gaifas, Brandon Le Bon, Ambroise Desfosses, Irina Gutsche

As electron microscopists, we are always keen in gaining a deep understanding of different image processing algorithms and workflows, and using state-of-the art software. Where necessary, we develop our own tools and share them with the community.
To enable interactive visualisation and annotation of cryo-ET data, we developed blik, an open-source napari plug-in built on the python scientific ecosystem. We also maintain a number of tools for working with established software suites: cs2star for Relion-CryoSPARC conversion, waretomo for batch processing with Warp and AreTomo.
Together with an open and international group of cryo-ET software enthusiasts, we champion the Teamtomo project, a community effort to develop a unified but modular ecosystem of libraries for cryo-ET image processing.
We also contribute to the development of the software for helical symmetry determination, helixplorer, and participate in solving structures of particularly challenging helical assemblies.

Collaborations:
– Leandro Estrozi, MEM, IBS
– Alister Burt, Genentech, USA
– Daniel Castaño Díez, CSIC, Bilbao, Spain

Multi-stress resistant organisms

Da Silva Catarina — 2024-08-23T17:41:54Z

Integrative structural analysis of multi-stress resistant organisms
Harald Bernhard, Lorenzo Gaifas, Eymeline Pageot, Ambroise Desfosses, Maria Bacia, Irina Gutsche

In parallel to investigating fractionated cell extracts of a multi-stress resistant organism by high-throughput single particle cryo-EM, as presented above, we seek to contextualise the obtained in vitro structural information by analysing the same organism using in situ cryo-ET, and to investigate structure-function relationships of selected complexes in more detail by classical cryo-EM combined with other imaging, biochemical and modelling approaches. One of our current model systems is Deinococcus radiodurans, chosen for its relatively large size, unusual morphology, non pathogenicity and extraordinary resistance to X-ray and UV radiation. An additional motivation for the choice of this specific bacterium is the possibility to closely collaborate with Joanna Timmins, an expert in D. radiodurans genome organisation and repair in response to irradiation. We recently set out to study D. radiodurans cell division, the associated cell wall synthesis and rearrangements, and the concurrent chromosome multiplication and segregation into the daughter cells using single particle cryo-EM, cryo-FIB/SEM, cryo-ET and cryo-soft X-ray tomography. At present, we concentrate more specifically on the DNA-binding and bending protein HU, the cell division protein FtsZ and the ribosome. However, the cryo-EM micrographs of cell extracts and the lamella tomograms contain a wealth of information that we may explore in future studies.

Collaborations:
– Joanna Timmins and Jean-Philippe Kleman, I2SR, IBS
– Linda Sandblad and UCEM, Umeå University, Sweden

Structural biology of cell extracts

Da Silva Catarina — 2024-08-23T17:28:44Z

Integrative structural biology of cell extracts
Eymeline Pageot, Maria Bacia, Irina Gutsche, Ambroise Desfosses

This innovative approach bridges the gap between the high resolution structural characterisation of highly purified, isolated biomolecules and in situ electron tomography. By removing the need for overexpression and purification, structural biology of native cell extracts holds unparalleled potential for applications. Emerging pathogens with unannotated genomes, uncultivable organisms, environmental samples containing numerous organisms—this method relies on cryo-EM imaging of heterogeneous fractions containing hundreds of proteins and complexes. It aims to simultaneously solve a large number of high resolution structures, annotate the corresponding genomes with the sequences derived thereof, and identify new essential complexes in organisms that are absent from databases. The challenge is the throughput and automation of this process: currently, it takes months to process a single heterogeneous dataset of this type, whereas it would be necessary to combine dozens of datasets corresponding to various molecular weight ranges to create a sufficiently complete atlas of the endogenous structures of a target organism. This project aims to lay the foundations for automation by exploring each aspect: from optimizing image acquisition to automating image processing for 3D reconstruction, and implementing AI-based tools for the identification and atomic interpretation of the solved structures.

Collaborations:
– Yohann Couté, EdyP, IRIG, Grenoble
– Linda Sandblad and UCEM, Umeå University, Sweden
– Virgile Adam, I2SR, IBS

Human Low-Density Lipoproteins

Da Silva Catarina — 2024-08-23T17:14:05Z

Structural investigation of the human Low-Density Lipoprotein
Tamás Földes, Madalena Branco, Maria Bacia, Ambroise Desfosses

Cardiovascular disease accounts for 32% of deaths worldwide and is considered the leading cause of premature mortality. For risk assessment and treatment, modern guidelines indicate serum low-density lipoprotein (LDL) cholesterol levels as the primary target. Instrumental in the metabolism and homeostasis of cholesterol and lipid transportation, LDLs are complex 17-28 nm nanoparticles comprised of a phospholipid membrane surface and a lipid core, wrapped by the amphiphilic apolipoprotein B-100. Solving the LDL structure at atomic resolution is particularly challenging due to their heterogeneous composition and flexibility.
Our consortium combines experimental techniques and molecular modelling to get insights into the structure of LDL. The experimental approaches provide data on specific individual aspects, and the molecular modelling integrates them into a comprehensive and dynamic overall model. While our first cryo-EM analysis revealed the LDL shape and core organisation, we are now collecting new data and using more intricate image analysis to achieve higher resolution. Additional structural information is being gained from neutron and X-ray scattering experiments, performed in ILL and ESRF, that can capture structural motifs at both larger and smaller scales. Our new computational approach, using both AlphaFold and classical molecular dynamics at a coarse-grain level, heavily relies on all these findings to construct a molecular model that is able to reflect the LDL structure and dynamics.

Collaborations:
– Judith Peters, ILL/LiPhy, Grenoble
– Karin Kornmüller, Medical University of Graz, Austria

Multicomponent chaperones for respiratory complexes

Da Silva Catarina — 2024-08-23T16:02:09Z

A long-standing project in the group is dedicated to investigation of structure-function relationships of two multicomponent chaperone systems involved in assembly of bacterial and human respiratory complexes, and thereby in antibiotic resistance and in Alzheimer disease respectively. Even though we have made great strides in understanding both systems, many questions still linger.

Unravelling the structure and the roles of the mitochondrial Complex I assembly complex in Alzheimer's disease
Catarina S. Silva, Ambroise Desfosses, Maria Bacia, Irina Gutsche

Worldwide research efforts to identify the factors driving Alzheimer's disease (AD) pathogenesis aim to find better ways to diagnose, delay and prevent the disease progression. For energy uptake, neurons rely on an efficient oxidative metabolism and are therefore particularly sensitive to mitochondrial dysfunctions. Respiratory Complex I (CI), the ﬁrst enzyme in the respiratory chain, is crucial for energy production driven by oxidative phosphorylation and is thought to be linked to AD pathophysiology. We use cryo-EM to investigate the human Mitochondrial Complex I Assembly (MCIA) complex, essential for the CI biogenesis. Indeed, the organisation of MCIA and the mechanism of its action on CI remain unclear, in part because the core components of the MCIA complex - ACAD9, ECSIT and NDUFAF1 – also perform multiple other cellular functions. ECSIT, for example, is involved in cytoplasmic and nuclear signalling pathways, undergoes post-translational modiﬁcations and has been reported to interact with amyloid-β (Aβ) producing enzymes. Together with our collaborators in ESRF, and making use of an integrative structural biology approach, we aim to elucidate in molecular detail the function of the MCIA complex in CI assembly, its roles in mitochondrial bioenergetics and its interplay with amyloidogenic Aβ, a hallmark of AD.

Collaborations:
– Montserrat Soler-Lopez, ESRF, Grenoble

Investigation of the molecular mechanisms of action of the enterobacterial LdcI-RavA-ViaA triad in stress response and antibiotic resistance
Moritz Kirchner, Madalen Le Gorrec, Maria Bacia, Irina Gutsche

To spread through our digestive system, enterobacteria must survive antibiotic exposure in the acidic and anaerobic conditions of the host stomach. Toxicity of the highly efficient aminoglycoside (AG) antibiotics, limits their use to severe infections only. Moreover, their activity decreases under anaerobiosis, requiring even higher therapeutic doses. Reducing AG doses should minimise toxicity and expand their safer use. To achieve this, it is essential to understand what makes enterobacteria sensitive to AGs in gastrointestinal tract conditions. Since many years, our group has been studying a tricomponent enterobacterial stress response system composed of an acid inducible lysine decarboxylase LdcI, its AAA+ ATPase regulator RavA and a RavA partner ViaA. This system was proposed to chaperone respiratory complexes, in particular CI and fumarate reductase, thereby facilitating AG uptake. However, although our collaborators confirmed that the ravAviaA operon was essential for bactericidal activity of AGs under anaerobiosis, its mechanism of action remained controversial. Recently, we discovered that RavA and ViaA are at the heart of a previously unknown pathway, mobilised in response to AGs under anaerobiosis and engaged in cell membrane regulation via direct binding to specific lipids. We demonstrated that RavA and ViaA locally modify membrane composition and morphology, thereby facilitating the entry of antibiotics into the bacteria in a respiratory complexes-dependent manner. This breakthrough has set the stage for further investigations of the molecular network that links the LdcI-RavA-ViaA triad to stress response, membrane homeostasis and remodelling, respiration and AG sensitivity. In this context, we use a combination of advanced optical imaging, single particle cryo-EM and cryo-ET to decipher the modes of action of the LdcI-RavA-ViaA triad in membrane biology and stress adaptation.

Collaborations:
– Jean-Philippe Kleman, M4D platform, I2SR, IBS
– Frédéric Barras, Pasteur Institute, Paris
– Daniel Castaño Díez, CSIC, Bilbao, Spain
– Mikhail Bogdanov, University of Texas, USA

Respiratory Syncytial Virus

Da Silva Catarina — 2024-08-23T09:16:58Z

Nanoscale exploration of the multiplication of the human Respiratory Syncytial Virus
Lorène Gonnin, Catarina S. Silva, Brandon Le Bon, Ambroise Desfosses, Madalen Le Gorrec, Maria Bacia, Irina Gutsche

Our group has a long-term interest in nonsegmented negative strand RNA viruses. After several years of studies of Paramyxoviridae (Measles) and Rhabdoviridae (Vesicular Stomatitis and Rabies), we shifted to Pneumoviridae and their most well-known representative, Respiratory Syncytial virus. RSV is the leading cause of infantile bronchiolitis and pneumonia worldwide, with the burden on elderly comparable to influenza. Whereas the freshly introduced vaccines target only the pregnant women and the elderly, the majority of population, including infants and children, lack vaccination and therapeutic options. To establish and spread infection, the virus amplifies its genome within infected cells and transmits it to neighbouring cells. The genomic RNA, enwrapped into a helical nucleocapsid, is transcribed and replicated by the viral polymerase. The resulting ribonucleoprotein particle (RNP) performs viral RNA synthesis inside the cytoplasmic viral factories, formed by liquid-liquid phase separation. Once enough RNPs are produced, they are transported to the plasma membrane for packaging into new virions. We have recently dissected the structural landscape of the helical RSV nucleocapsids in vitro by cryo-EM. The structures of the other viral proteins involved are also mostly solved, and the virion shell has recently been structurally characterised. However, how the different viral players cooperate, how they coopt their cellular partners, and how the viral cycle is regulated is yet largely unexplored. To achieve a spatio-temporal and mechanistic understanding of these processes, we joined a consortium investigating the RSV multiplication using a rich palette of complementary strategies. In our group, we apply a variety of electron microscopy techniques such as single particle cryo-EM, cellular EM, CLEM, cryo-FIB/SEM, in situ cryo-ET and cryo-CLEM. In parallel, we adapt and develop associated image analysis tools and workflows.

Collaborations:
– Marie Galloux, Julien Sourimant, Monika Bajorek and Jean-François Eléouët, INRAE, Jouy-en-Josas
– Marie-Anne Rameix-Welti, Pasteur Institute, Paris
– Lorène Gonnin, Linda Sandblad and UCEM, Umeå University, Sweden
– Max Renner, Umeå University, Sweden
– Takayuki Uchihashi, Nagoya University, Japan
– Tuomas Knowles, University of Cambridge, UK
– Cédric Leyrat, IGF, Montpellier

Theses

2022-11-21T15:10:04Z

All our theses

The list of PhD theses undertaken in the Microscopic Imaging of Complex Assemblies Group can be found year by year below (manual list).

Theses 2026

Moritz Kirchner
Molecular bases of a multiprotein assembly linking membrane biology to stress adaptation in enterobacteria
Doctoral thesis from the Communauté Université Grenoble Alpes, defended on April 23rd, 2026

Eymeline Pageot
Decoding chaos : a cryo-EM walk through Physarum polycephalum heterogeneous cell extracts
Doctoral thesis from the Communauté Université Grenoble Alpes, defended on April 21st, 2026

Theses 2025

Jahnavi Jangala
Structural insights into Siglec-10 receptor : a target for cancer immune modulation
Doctoral thesis from the Communauté Université Grenoble Alpes, defended on November 26th, 2025

Theses 2024

Lorenzo Gaifas
Tools and methods for interactive visualization and analysis of superstructural biological assemblies by cryo-ET : a Deinococcus radiodurans case study
Doctoral thesis from the Communauté Université Grenoble Alpes, defended on October 24th, 2024

Theses 2023

Lorène Gonnin
Structural and functional study of the respiratory syncytial virus nucleocapsid
Doctoral thesis from the Communauté Université Paris-Saclay, defended on June 1st, 2023

Theses 2022

Alister Burt
Cryo-electron tomography of bacterial minicells
Doctoral thesis from the Communauté Université Grenoble Alpes, defended on May 24th, 2022

Theses 2020

Matthew Jessop
Cryo-EM characterisation of an enterobacterial stress response system
Doctoral thesis from the Communauté Université Grenoble Alpes, defended on February 19th, 2020

Theses 2017

Diego Carriel
Structure-function relationships of the lysine decarboxylase from Pseudomonas aeruginosa
Doctoral thesis from the Communauté Université Grenoble Alpes, defended on May 15th, 2017

Access the full-content of our theses

If you want more details, note that the HAL-IBS website publishes the full content of thesis that are not under embargo or under a particular contractual obligation. The result is listed below, the display may take 1 to 2 seconds.
Please note that the theses of the last 12 months are not yet available on this site and theses prior to 2010 are not exhaustively listed.

Publications

2022-11-21T15:00:39Z

Our list of publications with peerReviewing, books and book sections since 2014 can be found below (data issued from HAL-IBS).
The display may take 1 to 2 seconds. To check the entire list, use the inner scroll bar.

Presentation

GUTSCHE Irina — 2022-11-18T08:11:12Z

Group leader : Irina Gutsche

Our group is interested in imaging macromolecular complexes and cells with the goal of gaining structural insights that would yield functional understanding of cellular processes. Our favourite imaging technique is cryo-electron microscopy in its variety of different flavours. We are using state-of-the art equipment available at the IBS EM platform and further afield, in particular at the Umeå Centre for Electron Microscopy (UCEM), in Sweden, to obtain images of our objects of interest. Once we have our images, we combine, adapt, and enhance available image analysis tools to solve the 3D structures of biomolecules. We synergistically apply complementary electron microscopy methods to explore biological samples with different levels of complexity.

While continuing to investigate the structure-function relationships of several macromolecular systems using 'traditional' single particle cryo-EM, we develop technologies aimed at simultaneously solving structures directly in cell extracts. In parallel, we analyse increasingly complex reconstituted or semi-purified systems by cryo-EM, cryo-ET, and modelling approaches, and delve into the cellular interior using cryo-FIB milling, cryo-ET, correlative methods, and complementary imaging techniques, ultimately bridging structural and cell biology.