Gareth Griffiths (GG): The very first EM course here was the EMBO course ‘Electron Microscopy of Nucleic Acids’. It was led by Hajo Delius who went on to be a group leader at EMBL for over a decade. That was in 1977 – the same year I started working at EMBL. Then in 1978 I went to a meeting in Toronto where the electron microscopist Kiyoteru Tokuyasu was demonstrating new techniques including methods for immunolabelling. This is where you highlight parts of a sample by using antibodies that bind to the areas of a cell or tissue that you’re interested in. The antibodies have atoms of a heavy metal – often gold – attached to them, which makes them show up clearly on EM images. When I got back to EMBL after that meeting I decided I was going to work on developing methods for immunolabelling. One of my colleagues put me in touch with Jan Slot in Holland, who was the first guy to learn these methods from Tokuyasu. I arranged to visit Jan for a week to learn from him, and within six months we had an EMBO course, with Tokuyasu and Slot!
How has the field of EM changed since the course began?
Yannick Schwab (YS): One way is the development of various techniques for 3D imaging with EM, and correlative approaches in which images from electron and optical microscopy are combined. EM went through a low period in the 1990s, linked to improvements in optical and fluorescence microscopy. But since then, improvements in instrumentation have really broadened the scope of what you can do with EM: we can do high-throughput, high-resolution EM tomography; we can reach ultrastructural resolution in large specimens, we can combine functional imaging at the fluorescence microscope with structural imaging at the electron microscope. Meanwhile, cryo-EM techniques have been steadily growing in impact since the 1980s, and are now an essential part of the structural biologist’s toolkit, too.
GG: The tools we use have improved a lot too – not only the microscopes but things like the diamond knives and microtomes that we use for cutting thin sections of a sample for imaging. When we first started the course we were using machines that didn’t work very well – it was like the one-eyed teaching the blind!
And how has the course changed over the past 40 years?
GG: Our course has always been focused on cell biology. The first few courses were really simple: it was more or less one technique and now it’s more like 12 or 15 different techniques – almost too many for a ten-day course.
How is the course structured?
YS: Usually we have lectures in the mornings, and we try to have a logical sequence starting with a very basic introduction, then going through the whole process of preparing samples, cutting sections for imaging, using advanced methods like immunolabelling, and then image acquisition. Then we go on to the more specialised techniques including 3D EM and correlative methods. We also give an introduction to cryo-EM – a method that involves rapidly freezing samples prior to imaging. Cryo-EM avoids the use of any of the chemicals required in conventional EM, enabling us to image native structures at high resolution. In our course it’s not possible to cover cryo-EM in depth – there’s a separate EMBO course on cryo-EM, led by Carsten Sachse. After our morning lectures, we go to the labs and students rotate through different workstations, covering the full range of experiments you would do with cellular EM. They do that for the first four days, and then the last six days it’s à la carte, so students design an experiment and book the different workstations they need to image their samples.
What’s special about this course?
YS: Even though the course is 40 years old, there’s a core of teachers that has more or less stayed the same. Another feature is that the teachers stay for the full duration. On most courses you invite guest speakers who leave after a day or two, but here most of the teachers stay all the way through to offer support and expertise, and for the students it’s fantastic to have that. The course is also quite long – ten or eleven days – so there’s a lot of time for people to discuss their projects and go really in depth. And I firmly believe that people leave this course with the ability to do things on their own. Some other courses are more demo-based, so you see an expert running the show and you don’t have much chance to do things yourself. Here it’s much more hands on, and we have almost a 1:1 ratio of teachers to students so you get a great level of supervision. I really believe that’s a unique aspect of this course.
GG: Coming back to EMBL is always unique because the organisation is phenomenal, there are people to organise everything and the setup for the practicals is amazing – there’s nowhere like it. We’ve held the course in many other locations but they don’t have the same level of equipment or the same infrastructure. Here there’s fantastic technical support and really top-quality people. So it’s a dreamland to be able to run a course here. On the other hand, the team of instructors has long experience in running the course in many other locations where the set of available instruments is not necessarily as extensive as it is at EMBL. That has never been a problem we couldn’t solve; on the contrary, it might even be better for students coming from various institutes to see how to apply advanced techniques even with older instrumentation. The real strength of the course therefore relies on this very flexible and adaptative team of teachers, and of course on the staff of the host laboratories. Wherever we have travelled to, we have always been lucky to be hosted by highly motivated and skilful crews.
Tell me about the teachers on the course.
YS: All the people we have teaching here are experts, and they’re also people who really enjoy teaching. They’re not paid to teach on the course so it has to be something they do out of passion. Up until now it’s been mostly the same gang of people but they’re starting to retire so new teachers are coming in.
GG: The students know they can ask us anything, we’re here for them. But what’s also important is that we have a wide network of friends all over the world in the EM community. Maybe a year or two after the course a student might come to us and ask, “Do you know how to do this?” And I might say, “Well, I’m not sure but maybe Heinz Schwarz in Tübingen knows – Heinz usually knows everything.” So then the teaching extends. It’s like being part of a family in a way.
Why is the course important?
YS: EM for cell biology went through this low period in the 1990s, and as a result we currently lack trained people to run facilities and progress in the field. I’m convinced that this course has been instrumental over the last few decades in providing the next generation of electron microscopists, and you can see that if you look at facilities both across Europe and worldwide. Many of the people in these facilities are alumni of the course.
GG: There must be at least 600 people who we’ve taught on the course here in Heidelberg, and over the years we’ve also held courses in several different countries so we must have taught well over 1000 in total. It’s a lot of people. Yannick is a good example of how someone can progress after taking the course. He was one of our star students in 2005 – he was incredibly enthusiastic and got some difficult techniques to work during the course itself, which was impressive. Then in 2007 there was a course in Singapore and one of the regular teachers couldn’t make it, so we thought, “Why don’t we invite Yannick?” and then he came to teach. He’s now been teaching on the course for ten years and has been head of the EM Core Facility at EMBL for the last five.
What about the social side of the course?
YS: We try to place everybody in the same hotel, so people eat meals together and have social events together. There are always opportunities to mix, or to discuss projects and career strategies. The format of the course really binds people together.
GG: There must be dozens of people who met on the EMBO course who are still friends today. We talk together, socialise together, have a drink together, so it’s a deeper feeling than just working together. Somehow we’ve collected a bunch of people who always have a sense of fun and that’s a really important part of it.
To study the effect of commonly used drugs on bacterial envelopes, EMBL scientists applied a biochemical assay using a colour reaction. The deeper the red, the stronger the disruptive effect of the drug.