Pushing the boundaries of the visible

Our cutting-edge technology platforms are key enablers of research at the FMI. One of the biggest of these, with the largest number of users, is the Facility for Advanced Imaging and Microscopy (FAIM). To find out more about the facility, and microscopy in general, we spoke to the joint heads of FAIM - Christel Genoud, who is responsible for Electron Microscopy, and Laurent Gelman, responsible for Light Microscopy.

Can you describe in a nutshell what the FAIM platform offers?
Christel & Laurent : Users of the FAIM platform - FMI scientists and collaborators - have access to a wide variety of high-end light and electron microscopes, as well as expertise in image analysis and high content screening equipment. Our team brings together diverse talents and takes a multi-disciplinary approach to microscopy. We not only provide training for users in handling our systems, but support them all the way through a project. We also offer weekly courses in microscopy and image processing. Our goal is to help scientists conduct successful projects, but also to equip young researchers with the knowledge and skills required to excel in their future careers in the field of microscopy.

Do you think FAIM provides a competitive advantage for the FMI?
Christel & Laurent : Having a cutting-edge microscopy facility has become a “must” for all leading scientific research institutes. But we can safely say that, for an institute of this size, the number of instruments, the portfolio of imaging modalities and techniques, and the number of experts supporting microscopy and image processing is quite exceptional, if not unique. We also benefit from close collaboration with the IT department and are well equipped to analyze and store the constantly growing volume of data generated through microscopy; and that’s crucial - the faster you acquire and process the data, the faster you publish!

What have been the most recent developments and successes within the FAIM?
Christel : Our cryo-electron microscopy center - shared with Novartis and operational since 2017 - has been a huge success. Our most important new cryo-EM system - Titan Krios - makes it possible to resolve protein structures at atomic detail without crystallization, filling a gap for our research at the FMI and also for drug discovery at Novartis. This year alone, we’ve already resolved 24 structures below 4 angstroms; for the FMI, this enabled us to solve scientific questions critical for the research of Nico Thomä, Jeff Chao and Franziska Bleichert.
Laurent : On the light microscopy side, the spinning disk confocal microscopes we’ve acquired over the last three years are true game-changers, enabling projects which were simply not possible before. Thanks to their sensitivity and speed, these systems allow us to acquire images of fluorophores in living cells on millisecond timescales, revealing intricate biological dynamics. For example, the groups of Susan Gasser and Jeff Chao can analyze the very fast movements of chromatin domains or mRNA molecules in living cells, using very little light to avoid any perturbation of the biological processes. Other groups could speed up their acquisition times by a factor of approximately 20x compared to classical confocals, while retaining excellent resolution and image quality. But we don’t just buy and use commercial instruments, we also helped the groups of Prisca Liberali and Antoine Peters to build a unique light-sheet microscope prototype for imaging organoid growth or embryo development.

What’s the most challenging aspect of your roles?
Laurent : Despite the fact that research has become highly “technical”, teaching at universities does not include much about technologies. Many students have little knowledge of microscopy when they start their PhD here, and they first need to appreciate the role of microscopy and the support we can offer. It is crucial for us to understand the users’ research goal so that we can help them to formulate the scientific question in such a way that it can be answered using one of our technologies. Designing the experiment with the user and setting up the system so that it really “works” can be really challenging - and exciting - depending on the project.
Christel : Another challenging - but also exciting - aspect of our work is keeping up to date with the latest technologies and knowledge in a highly dynamic field, where applications and instruments are getting increasingly sophisticated and specialized. Also, we have to lead and motivate a team of people with very different backgrounds and tasks.

How do you see the future of microscopy?
Christel & Laurent : We work in a very dynamic field. All the disciplines relevant for microscopy - physics, chemistry, but also computer science - are progressing rapidly, allowing for a mini-revolution nearly every 5 years! This fast pace of change will continue. More specifically, we think we’ll witness major developments in automation over the next few years - from sample preparation to image acquisition, image processing and data mining. We’ll have to invest even more in machine-learning-assisted approaches, robotics and high computation hardware. Single-cell approaches will require improved integration of imaging, genomics, proteomics and structural analysis.

Why are you personally passionate about microscopy?
Laurent : I am quite generally a technology freak! I feel lucky to work in a field where I’m regularly blown away by the advances in technology.
Christel : I love offering researchers the best technique possible to solve their scientific questions. Nothing is more rewarding than seeing a user amazed by an image showing exactly what he or she wishes.

About Christel Genoud
Christel holds a Master’s and a PhD in Life Sciences from the University of Lausanne. After postdoctoral studies in Neuroscience, she worked for a company specializing in electron microscopy accessories, first in Oxford and then in San Francisco. She joined the FMI in 2008 and has been joint head of the FAIM since 2010.

About Laurent Gelman
After gaining an Engineering degree in Biochemistry and a MSc in Immunology in Paris, Laurent did his PhD in Molecular Biology at the Institut Pasteur in Lille and the IGBMC in Strasbourg, where he also did postdoctoral research on in vitro transcription assays. He then moved to the University of Lausanne, where he used advanced microscopy techniques to study gene regulation in living cells. Laurent joined the FMI in 2006, and has been joint head of the FAIM since 2010.