Last summer, the twenty-seventh annual course on Imaging Structure & Function in the Nervous System was held at Cold Spring Harbor Laboratory. We chatted with the 2017 co-instructors Florin Albeanu, Michael Orger, Lucy Palmer, and Philbert Tsai to gain an inside look into the long-running, intensive course First, we asked about a day-in-the-life of an Imaging trainee, and learned they literally build microscopes from scratch during the three-week course:
Phil: The typical daily schedule changes from week to week but overall, we try to avoid an information overload. For example, in the first week, we don’t like to bombard the trainees with a lot of information all at once so the schedule is kind of lecture, practical, lecture, practical. The practicals are lab bench exercises that allow the students to tinker with stuff and effectively learn how to build a microscope from scratch.
We begin at 9 AM with three hours of lectures on the fundamental of optics and methods of microscopy to ensure everyone has a good foundation of the basics. After lunch, the students spend two to three hours working on optical bench rails and building small imaging systems. The systems become more complicated with each practical, from simple lens imaging to a full wide-field microscope to a laser scanning microscope (which is a bonus for some students because it can be turned into a confocal microscope). Later in the afternoon, we have another lecture that is oftentimes followed by questions that came up during the practical. There are questions the students will only ask if they’ve actually been confronted with the fact that something doesn’t work the way they thought it would; if we jumped from one lecture to the next without a practical in between, those questions would not come up and the depth of conversations would not be the same. By the end of the first week, the students move into the main lab and start working with million-dollar microscopes, at which point they have a better idea of what’s going on behind the lens.
Michael: As the students transition from the optical bench exercises to the microscope, the first step is to conduct experiments designed to better understand the fundamental principles of what they’ll do in their own work. They measure the noise characteristics and resolution of the microscopes so they understand the possibilities and limitations in their experiments in a very general way. When they’re using the microscopes in the course, they’re really learning how to understand the measurements they’re making and what they mean.
Florin: During the second and third week of the course, there are a lot of applications of the basic ideas taught in the first week. And in many cases, the trainees realize that exactly the same concepts are packaged in different microscopes. Fancy up-and-coming microscopes, in fact, use the same two or four lenses again and again.
Lucy: In the third week, the students also work on their own course projects, which they can pursue solo or as part of a group.
Michael: The final assignment of the course, right before the lobster banquet, is for the students to present the results of their projects or anything else they want to share regarding what they learned during the course.
Phil: Outside of the course projects, we always have them work in at least pairs because we feel the social aspect is important. When the students do the optical bench exercises, they work in groups of 3 or 4 which indirectly becomes a team building exercise. A majority of students never thought that they could build a microscope. So there’s this team effort to overcome the hurdle of “We’re supposed to build a microscope from scratch in three hours? No way!” And they all end up doing it.
Florin: They also realize that the microscopes they build, in many cases, can do as good a job as the pricey microscopes on the market. That knowledge goes a long way. If funding is a limitation, they have the experience to build their own microscope and understand exactly how everything works in it.
Phil: The microscopes the students build use $40 lenses and $50-100 scanners, so they do have certain limitations. They’ll never be as good as a well-engineered, million-dollar microscope, but a homemade version can get you 95% of the way there. The critical thing is realizing what that last 5% is and whether it’s worth hundreds of thousands of dollars. When you’re doing cutting edge research, it’s important to understand where the critical components are so you know where to spend your money and where not to waste it.
Florin: Getting the students to play with the lenses themselves actually makes this much more obvious. More than that, as you look at the microscope, you realize the precision of the microscope is the precision of your hands, of your alignment, and that’s empowering.
Michael: The students also have the opportunity to try new things and test out ideas. We have a combination of commercially built equipment--a lab of ten of the nicest microscopes at their disposal--and equipment just for developing and trying new things. Very often, actually, the course projects aim to make a particular method a little bit better.
Phil: Microscopy is one of those topics that falls between traditional departments. On the physics side, the basics of how a microscope is constructed are taught but most physics departments don’t teach their undergraduates about laser scanning microscopes or confocal microscopes. Biologists, on the other hand, use these microscopes all the time but are unfamiliar with the working principles behind the microscopes. Over the years, alumni have told us they don’t know where else they could have learned all this, that the course is the only place they could find all this information.
Florin: Also, a physics book on optics can be a little dry. So if you are a biologist trying to understand imaging, learning through a book can be a long path. Being part of a course like this exposes you to all kinds of tools, principles, and techniques in optical imaging, then you actually use them to build a device.
Michael: You can read a book about optics but until you get your hands on things, it’s really hard to fully grasp the concepts.
Invited speakers play a major role in CSHL courses, including the Imaging course. Next, the instructors discussed the caliber of the 2017 speakers and their contributions to the course and its trainees.
Michael: We schedule the invited speakers on a bit of a gradient: speakers at the beginning of the course cover basic methodologies and those toward the end talk about more specific applications. Our speakers are really, really great. A number of them have been coming to the course for over a decade, possibly even two.
Phil: And they evolve. Their talks are always on their most recent research as well as what they’ve done in the past. We invite them back because they enjoy this crowd and its interactive-ness. These are conference-level speakers who give colloquia to departments or universities in front of hundreds of people. The course trainees get to be in the room with them, have lunch with them, and ask them whatever questions they have. That’s a real opportunity.
Michael: It’s a completely different experience than if the person came to your university and gave a talk. In the course, the students can really ask the speakers whatever they want. And almost all of the speakers like to stay at the course for extended periods to spend time with the students.
Phil: Many of our speakers are the ones who started this field.
Florin: Sometimes new projects arise from these interactions; course alumni have joined the labs of invited speakers they met in the course.
Phil: Let me phrase it this way: it’s the chance for an interaction that sometimes changes the course of a career. It’s the types of conversations that are had in a crowd of 12 people, in an atmosphere that encourages questions, ideas, and curiosity. There have been times when a student might ask, “I’m interested in X. Could X be used for Y?” And when a person who created X and uses it every day answers with, “Actually, X would be ideal for Y,” it’s very encouraging. The student follows a new research direction because of that one exchange.
We then asked how the course has changed over years:
Lucy: Phil is probably the best person to answer since he’s been with the course for 15 years.
Phil: I’m the best and worst person to answer this because I have a terrible memory! Fundamentally, I think the course hasn’t changed that much over the last 15 years. This biggest evolution has been fine-tuning the iterative back-and-forth of listening to lectures, followed by tinkering in the lab practicals, followed by more lectures and Q&A sessions. I think we’re in a pretty good place with that now.
Lucy: The course content also evolves as new approaches come out. We really try to stay on top of the field with different preps and techniques, so the students are always exposed to cutting-edge material.
Phil: More and more students are coming to the course with the word ’microscopy’ already in their background. Ten to fifteen years ago, students applied to the course because imaging was becoming big and was gaining momentum in the field of neuroscience – but not everybody was yet doing it. Today, imaging is starting to dominate. You’ll be hard-pressed to find a core facility or university without a two-photon microscope. As a result, the students now have some prior two-photon imaging or confocal imaging experience, and they want to learn what’s going on inside the microscope when they adjust settings. So the things we teach in the first week haven’t changed much. And despite students having done microscopy at their home lab before arriving at the course, they still gain quite a bit from the material taught the first week.
Michael: I think there’s been an increased focus on in vivo preparation. When I was a student of this course in 1999, there was a lot of cell culture and various other preps. But imaging activity on the cortex of a mouse was not something we did.
Phil: It was more limited to in vivo slices and cell cultures.
Lucy: Synthetics.
Florin: Funnily enough, things that were talked about in the course 10 to 15 years ago as dream projects are actually being done now in the class by students. And we still talk about “the new dream experiment” that will probably be implemented in the next decade by people involved in the course now.
As one of our most competitive courses, we made sure to inquire how applicants might increase their chances on becoming one of the 14 to 16 scientists each summer who are accepted into the course.
Michael: We look for applicants who are new to imaging and understand some of the problems they’re facing, but don’t yet fully understand what they’re doing. We want to train people who will be able to return to their labs and quickly take advantage of what they learned in the course. A lot of information is taught during the three weeks so it’s important that students can attend the course, understand why they’re learning what they’re learning, and go back to their labs to directly apply their newfound knowledge. This way, the information is reinforced as soon as possible.
Florin: We also look for applicants who are about to switch fields or start a new project.
Michael: We try to accept a mixture of students in terms of scientific background. We have had some students from physics backgrounds who have never seen a biological specimen, but have a firm understanding of how some elements of microscope systems work. And vice versa. It’s great to have a mixture like that because the students learn not just from the instructors, speakers, and TAs, but from each other. They can ask each other questions and share their knowledge.
Applicants’ personal statements should really express how the course is going to benefit their experiments or, even further, their labs. Of course, we want students with great scientific backgrounds, but the personal statement is less about selling yourself as a scientist and more about how this course is going to help you to do science better. For example, if you’re in a lab that is just starting to set up imaging but doesn’t have an electrophysiologist, that student’s participation in the course will have an impact even beyond their own research projects.
Another important thing to note is that every year we reject a bunch of great students. If you really want to take this course and think this is what you need, don’t give up. We consider persistence a big positive. So if an applicant states “I applied last year and didn’t get in and now I’m applying again,” it catches our attention. Besides wanting a group of motivated students who are fun to work with and enthusiastic about the experiments, we want people who really want to take the course.
Our chat closed with the co-instructors answering, “What’s your favorite moment from the course?”
Florin: It was my first encounter with the course. In 2006, I came in as a TA and was supposed to build a device in a short amount of time. Clearly, I was terrified dealing with the parts, but the instructors at that time said, “don’t worry, it’s going to work out just fine.” And indeed it did. Here, you are surrounded by extremely enthusiastic people whose encouragement makes a lot of things happen in a very short amount of time.
Phil: My favorite moment happens every year and it changes in flavor: it’s that moment when the students, who have been working on a rig for hours, struggling with noise and all sorts of other stuff, finally obtain a fluorescent image. They put together this scanning microscope themselves from a table of random parts and spent an hour aligning it, and now they see a high-quality image. They literally scream and jump for joy. They’re taking pictures of their microscopes and the image with their phones, posting it on Facebook, texting it to their loved ones and colleagues. It’s the excitement of realizing that they’re capable of something they didn’t know they were capable of just a few hours ago.
Michael: A lot of great moments happen throughout the course but one thing that is a pleasure to see takes place some years after a student’s been in the course. I see them post on Facebook about their new publication, and actually see the imaging they came to the course to learn. It’s always very satisfying to be reminded that the course has an impact on the students beyond just the three weeks.
Lucy: I have quite a lot of favorite moments from when I was a student in the course, and now as an instructor. As a student, it was building my own two-photon which was amazing: I was elated when I took the image. And now as an instructor, my favorite part is seeing all the students get to that same pinnacle and realizing they can do it. I enjoy seeing the motivation and excitement in students when they’re able to address a question they’ve always wanted to address.
The Imaging Structure & Function in the Nervous System course this summer will take place between July 24th and August 13th. Applications are being accepted until this Sunday, April 15th here. For an introduction into the course from a trainee, be sure to read our Q&A with 2017 Alumna Janani Sundararajan.
For more conversations with other course instructors, check out the rest of our A Word From series.