Institut de Biologie StructuraleGrenoble / France

Contact person(s) related to this article / GUTSCHE Irina

Presentation of the Microscopic Imaging of Complex Assemblies Group (MICA)

Group members

Irina Gutsche (CNRS Researcher, MICA group leader)
Ambroise Desfosses (CNRS Researcher)
Maria Bacia-Verloop (CNRS Research Engineer)
Madalen Le Gorrec (CNRS, Assistant Engineer)
Karine Huard (CNRS, Engineer)
Alister Burt (UGA, 4th year PhD student)
Lorenzo Gaifas (UGA, 1st year PhD student)
Yoan Duhoo (CNRS, postdoc)
Lindsay McGregor (ESRF, postdoc)

Alumni

Matthew Jessop (ex-PhD student, now at the Cancer Research Institute in London)
Jan Felix (ex-postdoc, now at the VIB in Ghent)
Angelique Fraudeau (ex-engineer, now in EMBL Grenoble)
Clarissa Liesche (ex-postdoc, now in a private company in Berlin)
Ladislav Bumba (ex-visiting scientist, now back to his lab in Institute of Microbiology in Prague)
Megghane Baulard (ex-engineer, now in a private company in Lyon)
Diego Carriel (ex-PhD student, now in a private company in Lyon)
Eaazhisai Kandiah (ex-postdoc, now in ESRF)


From left to right: Karine, Clarissa, Jan, Irina, Matt, Alister, Angélique and Ambroise

Activities

Our small group established in 2019 is interested in imaging macromolecular complexes and cells with the goal of gaining structural insights that would yield functional understanding of cellular processes.

Our favorite imaging technique is cryo-electron microscopy: we are using state-of-the art equipment available at the IBS EM platform and further afield to obtain images of our objects of interest. Once we have our images, we combine the most recent image analysis tools to solve the 3D structures of biomolecules. In recent years, we have solved structures of several challenging proteins and complexes, some of which were purified and biologically investigated in our lab, and others provided by collaborators (here we can show a figure with a mix of structures).


Some recent structures

While we continue investigating the structure-function relationships of several biological systems with «traditional» single particle cryo-EM, we are critically aware that the bottleneck of all in vitro structural techniques is sample preparation: the object of interest can for instance fall apart during purification, lose its cellular partners or a ligand, miss an essential posttranslational modification and change its oligomeric state. Therefore, we are now developping methods to solve structures directly from cryo-EM images of heterogeneous samples. Altogether, this methodology should enable investigation of the cellular structural proteome in its native state. This project is driven by Ambroise Desfosses, and progressively involves more and more people from the group.

The method of choice to address the 3D structure of biomolecules in their cellular context is undoubtedly cryo-electron tomography. We took our first steps into the world of cryo-ET with both in vitro reconstituted systems and bacterial minicells. We quickly realised that in addition to experimental difficulties, the major problem that newcomers into the cryo-ET field have to face is that optimal processing workflows in cryo-ET and subtomogram averaging are relatively complex and often require combination of diverse software packages. Thus, two PhD students in the group, Alister Burt and Lorenzo Gaifas, create and share their cryo-ET automation, analysis and visualisation tools with the growing cryo-ET community. They also established and maintain a collaborative online resource http://teamtomo.org for sharing knowledge and tools related to cryo-electron tomography data processing.

In addition to cryo-EM, we also use a variety of complementary methods from phenotypic analysis, through biochemistry, biophysics and X-ray crystallography, to advanced optical imaging. From a biological standpoint, the group’s research is mainly centered on microbial stress response, signalling and sensory adaptation. We are lucky to work with an extensive network of local, national and international collaborators.

Current funding

2021-2025 H2020-MSCA-ITN
2021-2022 Modélisation du vivant - AAP 2021
2020-2023 GRAL Pilot Project
2019-2023 ANR DecRisP
2015-2021 ERC Consolidator grant

Publications

The complete list of our publications is available here.