Transitions in development – an interview with Giulia Quattrocolo

Giulia Quattrocolo is an Associate Professor at the Kavli Institute for Systems Neuroscience in Trondheim, Norway, where her group studies neural circuit development. Notably, Giulia's work is providing insight into the role of Cajal-Retzius cells, a transient population of cells that are present in the hippocampus during postnatal development. We met Giulia over Zoom to discuss her career path so far. She told us about how she first became interested in neural development, how she developed her research niche during her time in the USA, and her childhood ambitions to become a volcanologist.

Image courtesy of Geir Mogen, Kavli Institute for Systems Neuroscience, Trondheim, Norway

Let's start at the beginning, when did you first become interested in science?

My interest evolved over time. Originally, I wanted to become a volcanologist and go around the world to study volcanos. However, my mom wasn't exactly excited about the idea of me going into volcanos and, although it's a fascinating career, I didn't really know what it entailed, because I didn't get the opportunity to study geology in school. Later, I went to a scientific high school where we had five years of biology. I became really interested in genetics, which is what I went on to study at university. But, in the second year of my biology degree, we had a general physiology course, and we started to talk about the Pacinian corpuscle. I thought it was the coolest thing I'd ever heard. From that moment on, it has pretty much just been neuroscience for me!

What first drew you to neural development specifically?

During my Master's in Italy, I was paired up with a PhD student and we would talk about his experiments. The lab was interested in understanding sodium currents in the neurons of the parahippocampal formation, and we started to think about when the different components of these different sodium channels come online during development. So, we started to do some experiments at earlier developmental time points. Because of that, I started to read about development more. I thought development was very cool for a couple of reasons: firstly, you don't really have to go in and do a lot of manipulation, you can just look at what physiologically happens when the animal is growing, and secondly, everything that happens in development will have an effect on the animal for their entire life. So, I wanted to understand how all these neurons come together during development and set up circuits to produce specific functions.

After your Master's, you completed your PhD at Northwestern University in Chicago, USA. How did you find the experience of moving to a new country?

It was intense. I had only been to the USA once before, when I visited New York for a vacation, and I'd never been to Chicago. I think it would have been even more overwhelming if I hadn't participated in Northwestern's summer school program for international PhD students. We arrived one month before the course started, and we took some English classes and some cultural classes. We were also shown around the city and the campus, and generally allowed to integrate into life there more smoothly than if we had just arrived and started with our rotations and classes straightaway. Because we were all international, we were all in the same boat, so I think that really helped to create a network of friends. But of course, labs and departments in the USA are very different from those in Italy. Other than my Master's thesis, I had very little experience of working in labs, and I found that the approach to science at Northwestern was quite different. Even the relationship between supervisor and students felt different; in Italy those relationships feel quite distant (or at least they were like that during my time there), while in the US they're much more friendly. So, the atmosphere was quite different from what I had experienced before but, overall, it was easier than perhaps I would have expected.

How did you navigate the lab rotations to ultimately choose a PhD lab and project?

The program at Northwestern required us to do one rotation every quarter; I think this is very common in the USA. It was recommended that we set up the first rotation before starting the course, so I contacted Gianmaria Maccaferri, who was working on the hippocampus. He was studying a weird cell type, called the Cajal-Retzius cell, that is present mainly during development in the cortex and in the hippocampus. The hippocampus was an area that I was interested in, since I had worked on the entorhinal cortex for my Master's. The project was also related to development, and it involved doing in vitro physiology, which is what I was really interested in at the time. So, I set up the first rotation with him, and that's actually the lab that I ended up joining because I was really happy with the project and with him as a supervisor.

I did the other two requested rotations; the second one was also really interesting, but it was less about development, and by the time I did the third one I had already decided to join Gianmaria's group, so I joined a lab that was doing immunochemistry and anatomy so that I could learn those techniques and apply them in Gianmaria's lab. For my PhD project, we used in vitro physiology (mainly paired recordings, optogenetic stimulation and pharmacology) to see which cells were talking to the Cajal-Retzius cells, and which cells the Cajal-Retzius cells were talking to. We were able to map the local circuits in the CA1 region of the hippocampus, which was something that nobody had ever really looked at. That sparked my interest in Cajal-Retzius cells, and I'm still working on them in my lab today.

After your PhD, you moved to Gord Fishell's lab at New York University (NYU) and then returned to Europe to work in Trondheim with Edvard Moser. What did your postdoctoral work involve?

I knew I wanted to keep working on in vitro physiology, but I also really wanted to join a lab that was devoted to developmental neuroscience. Gord is one of the best in that field, so I decided to join his group. My main project in Gord's lab was trying to understand how extrinsic and intrinsic factors control the integration of interneurons in a circuit. We took interneurons from the neocortex at postnatal day 0 and transplanted them into the hippocampus, and we took the interneurons from the hippocampus and put them in the neocortex. Despite being found in different regions of the brain, these interneurons express very similar proteins and form similar circuits, so we wanted to test whether there were any consequences of transplanting them back and forth. We found that some properties of the neurons were dependent on the cell type, while other things were more influenced by what region the cells were transplanted into. For example, there were some cell types that only expressed specific proteins when they were in one of the two regions, not when they were transplanted into the other one.

During that time, I started work on what would be my bigger project, about Cajal-Retzius cells. Cajal-Retzius cells are a transient population; they disappear from the neocortex very early on, but they survive in the hippocampus for much longer. Why does this happen, and what are these cells doing there? My idea was to kill these cells in hippocampus, to make the hippocampus more similar to the neocortex, and see what happens; if these cells are completely useless, then nothing should change. I started that project in Gord's lab, but then Gord moved from NYU to Harvard, and for personal and scientific reasons I decided not to go with him. At the time, my husband was also a postdoc at NYU, and I was at the end of my visa, so if we moved to Boston, I would have to apply for a green card. We always wanted to return to Europe, so we took it as a sign of the universe that it was time to come back. We both applied to labs here at the Kavli Institute; I emailed Edvard Moser and explained to him that I really wanted to study the function of the hippocampus when you remove the Cajal-Retzius cells, because I believed these cells were important for hippocampus development. I was very lucky, because he said I could join his lab to continue working on this project.

How did your time in the USA influence your career?

I think it was good to be in the USA and do research there for a while, because it's quite a different environment from Europe; it's very high paced, and there is a lot of pressure, which seems to trickle down from the heads of the departments a bit. I've never been in a lab where I felt an immense amount of pressure, but there was still this intrinsic environment where people really wanted to work hard, and where people spent a lot of time in the lab. I think it was a bit different when we moved to Europe, where it's a little bit less intense, in a good way. I think there's a more family-friendly environment in Europe, especially in Norway. For example, nobody puts a meeting after 4pm, because they know that schools and kindergartens close at that time.

I was very spoiled when I was in New York, because I would order something and then receive it the next day. By contrast, Trondheim is considered a remote location, so getting things here sometimes takes more time. Overall, I try to keep the good things from the USA with me, and maybe pass them on to my lab. But I also really appreciate the importance of things like maternity leave, which is pretty much impossible to get as a postdoc in the USA.

You remained in Trondheim to establish your own lab at the Kavli Institute for Systems Neuroscience in 2021. How did you form your research niche for your group?

I pretty much continued my postdoctoral research, as when I joined Edvard's lab I had my own project, which was very peculiar compared to the main line of research of his lab. But I think that my research fits the department well; most of the people here are working on the hippocampal region and the function of its circuits, whereas my interest is more focused on how different cell types contribute to circuit formation during development. So, my work nicely fits with the overarching direction of the department, as we focus on the same brain region, but I can avoid competing internally.

Can you summarize the research themes of your group at the moment?

I'm quite well funded at the moment, so we have several lines of research. The biggest one, for sure, is the one on Cajal-Retzius cells. Last year, we published a paper in which we ablated Cajal-Retzius cells from the postnatal hippocampus and showed that this produces layer-specific changes in spine number and spine type, as well as in synapse-related proteins and genes. We are now expanding on that from the functional point of view, so there are people in the lab who are recording place cells and doing behavioral experiments to study how the hippocampus is affected in these animals. From the molecular point of view, we are trying to deepen our analysis on synaptic proteins and synaptic changes, to understand what is causing all the changes we see.

The layer-specific synaptic changes that we have found while studying the effects of Cajal-Retzius cell ablation suggest that the different layers have different mechanisms that regulate synapses. Furthermore, if you compare animals at different time points, you clearly see changes in synapses and the synaptic content. This really sparked our interest, and we have started studying synaptic maturation. Are all synapses created equal, then start to differentiate more during the maturation of the circuits? Or are there already a lot of differences at earlier time points? To address this, we are trying to study synapses at the very early stages so that we can understand how this maturation process happens, and how the expression of different proteins affects axonal targeting and the function of the circuit.

What were your most important considerations when looking for group leader positions?

My husband and I did most of our searching during the pandemic. We tried to apply to places where they had more than one position, and we mainly applied in Europe. We did apply to some places in the USA, but we weren't keen on the idea of moving back there again. We tried to apply to departments where we knew people who were doing good work, and where we thought we could contribute something new. We got two offers, one from this department and one from another department abroad. They were both really good offers, but we were never able to visit the other department because Norway had closed borders, which meant we would have no insurance if we traveled, and we didn't want to take our kid with us because it was early in the pandemic. So, I think that influenced our decision. We were also very happy here at the Kavli Institute; we were both already very independent in our postdoctoral labs, and staying here also meant that we didn't need to re-derive all the mice! So, staying in Trondheim was a good choice, both personally and scientifically.

What has been the most challenging aspect of transitioning to a group leader role?

This may sound a bit silly, but when you're a postdoc, you do your experiments and you think: ‘Oh, I've done loads of experiments today, so I've worked hard.’ When you become a group leader, especially at the beginning when you're hiring, buying stuff for the lab and setting up the protocols, you're not doing many experiments. So, I went home every day thinking that I hadn't worked, and that I hadn't achieved anything. Luckily, I don't experience that anymore, otherwise I would feel like I haven't been working for the last four years! So, the main challenge is that you almost completely change your job – you're still doing science, but in a completely different way. The extent of this change depends a bit on how big the group is, and on your approach. I was quite lucky in terms of funding, so my lab got big quickly. This meant that it wasn't necessary for me to do experiments, and instead I had to manage the lab and mentor all the trainees.

Did you get any sort of mentorship or training through the institute to support the transition?

In 2021, when I got my first big grant and started my lab, I also became part of Norwegian University of Science and Technology's (NTNU) Outstanding Academic Fellows Program, which is designed for new group leaders. We have a couple of meetings per year where we discuss issues such as mentorship, grant writing and supervision. Sometimes we simply take solace in the fact that we're in the same boat, but other times we can offer help if one of us has experienced the same problem and found a solution. Through that program, I also had an international mentor who I could pick. My mentor has been extremely helpful in not only discussing the science, but also how to navigate the department's politics and deciding which battles I want to fight.

What do you enjoy most about running a research group?

I like the fact that I can run a lot of projects at the same time. During my PhD, I was pretty much the only person in the lab for a very long time, so I didn't really get to collaborate. If I was still working on my own, it would take me years to explore all of my ideas. Now, because I have more people in the lab, we can just run all these lines of research at the same time, which is very exciting. They also compensate for each other; sometimes one project is going a bit slowly, but another one is going faster and giving really great results. So that gives a nice feeling overall.

This will sound weird, but I also really like writing grants. I think it's an exciting time, when you have an idea and you have to put it in writing. You also have an excuse to spend a lot of time reading. In that moment, you don't know that it's not going to be funded, or that it's not going to work, or that it's going to be a headache to do it. You just have the excitement of this new idea.

You mentioned that your group grew quite fast. What is your approach for hiring new team members?

We have to advertise everything externally through Jobbnorge, which is the main jobs website in Norway. When the applications come in, I select a shortlist of five to ten people to do a short, 15-min interview where I usually ask four or five questions. From that, I refine it down to a few candidates, and I invite them to do a scientific presentation for the current members of my lab. I do a second interview with them, and I also set up a few meetings with people in my group. This allows the candidates to ask about life here, to ask questions about me that they don't want to ask me directly, and to get a feeling about if people are happy or not. I think people are quite happy in my lab, so hopefully people can see that during the hiring process.

What advice would you give to people starting their own labs?

Try to create a supporting network early on. I was lucky because I was in the same department as I was before, and I am married to someone who also started as a group leader at the same time, but it was still quite a lonely period. You go from being a postdoc in a lab, where you have meetings and events as a group, to a situation where the whole group is just you for a while until you can hire someone. I remember that, in those first weeks, I was just sitting in my office by myself for the whole day without talking to anybody. So (and this is particularly important if you're moving to a new place) try to find a colleague that can offer a helping hand, or even go out for a drink or something. Otherwise, I think the task is quite daunting. You're starting to do a job that you've never really trained for, and I think that having to do that all by yourself makes things even harder.

What is your approach to mentorship within your lab, and have you had any significant mentors who have influenced this?

Everybody in my lab has weekly meetings with me. These meetings are about an hour long, and don't have a fixed format. Sometimes the lab members bring presentations and data, and we look at figures together. But other times we might talk about how to set up an experiment, or about careers. It's an hour in my calendar that is dedicated to them, when they know that we can talk about whatever they need. I have to say, this is pretty much a copy and paste of what Gord did in his lab. Gord has been extremely successful, which suggests that his approach works, but on top of that I think that people were extremely happy in his lab. Everybody had their own project, and we could collaborate, because everybody had their own question. So, there wasn't competition, and instead there was a really nice exchange of ideas. This is what I'm trying to achieve in my lab.

I also make sure to discuss my expectations when I'm hiring people. During the interview, I ask them about their relationship with their current mentor, and what their expectations are. I then explain my approach and my philosophy, so that we can both assess whether we will work well together.

Finally, what do you enjoy doing outside the lab?

I have a child who is almost six, so that takes up a lot of time! But I like to read a lot, especially about women in history. I also like to travel a lot, and to read about traveling. For example, I was in London with my family a few weeks ago for the Silk Roads exhibition at the British Museum.

Giulia Quattrocolo was interviewed by Laura Hankins, Reviews Editor of Development. This piece has been edited and condensed with approval from the interviewee.