Giorgio Gilestro

Giorgio, you mentioned that the IMP is your 'real alma mater'. How did you come across the IMP in the first place and what made you choose Barry Dickson's lab for your PhD?

I have always been a reductionist at heart and I was impressed and fascinated by how the neurobiologists of the time had managed to strip an enormously complex problem (the wiring of a brain) to its bare minimum (the decision of a neuron to turn left or right). Even now, reductionism is probably what fascinates me most about science: it pushes us into simplifying problems to their minimal terms. It's almost an art.

I knew I wanted to study axon guidance in a reductionist model and the choice was between C. elegans and Drosophila. In all truth, I was actually drawn more to C. elegans back then but, in hindsight, I am extremely glad I chose flies instead. Barry had an amazing record on the field, and his laboratory was simply the best laboratory to join in terms of impact and ambition for someone who wanted to study axon guidance in Drosophila.

How important were these years as a doctoral student for your future career? What did they teach you that you find most useful?

Before starting my PhD at the IMP, I worked for four years in a laboratory in Italy studying the cell biology of axon guidance. I embarked on a lab internship during the summer of the first year of undergraduate studies, and that experience zapped me on the forehead as if I had walked the road to Damascus: I never returned back to classes after that summer and spent all remaining four years working full time in the laboratory. So, when I started my PhD, I already had a decent technical background but, boy, how much did I learn on the scientific aspects! 

I think two aspects were unique to the place back then: the genuine multidisciplinary interaction and the sheer amount of talent among my peers. The Monday lunch seminars were not simply well attended: we were all looking forward to them. At those seminars, I've learned that the project one works on has actually little importance and one could find wonder and challenge tackling any scientific matter, as long as the important questions were being asked. Never in my life have I met a similar level of genuine scientific interaction and I would have no idea of how to re-enact that atmosphere. I think it was a magical mix of appropriate critical mass and leadership by example. Kim (editor's note: Kim Nasmyth, IMP Director 1997-2006) and the PIs were the first ones to sit at those seminars. As for the people: it just felt so intellectually stimulating being surrounded by so many enthusiastic and talented individuals, from PhD students to PIs.

Having said this, not everything was perfect back then, but the IMP taught me to be bold and critical, so I realised there were certain aspects of that culture that I wanted to make my own and others that I wanted to leave behind. There is no doubt the combination of those two made me the scientist I am now.

For your dissertation, you worked on the nervous system of the Drosophila embryo. What made you become interested in behaviour rather than development, and how did you end up studying sleep?

I've fully lived the transition of Barry's lab from development to behaviour, so there is no doubt that the growing excitement around me must have played a major role in shaping that decision. It was also a period of an underground fly renaissance as it was becoming clear worldwide that Drosophila would soon emerge as the new model of choice to study neuroscience, even before Janelia was born (the RNAi library certainly contributed to that movement, even though it was initially conceived to be used for yet another axon guidance screening in the eye!).

On top of that, I was especially drawn by behaviour because it provided a strong polymath side: there were problems that had to be solved building new devices, new paradigms, new software - experiments were literally created from the bottom up. It felt a bit like being a nuclear physicist of the 1940's: you needed to invent your own tools before you could actually do experiments. So I knew I wanted to go into behaviour for that reason. As for sleep, it was probably more of a strategic decision, to be frank. I knew I wanted to go off the beaten path and sleep was a perfect opportunity. There were literally no Drosophila sleep laboratories in the world yet and that made it a great potential future niche for me. 

Can you outline briefly how your scientific career progressed after you graduated in Vienna?

I applied for a postdoc to the laboratory of Giulio Tononi and Chiara Cirelli at the University of Wisconsin-Madison. That was not a fly lab but they were running one of the most respected and successful laboratories working in the sleep field at the time, focusing on rodents and humans (and they still are). I joined UW-Madison at the end of 2006 and things went fast after that. In less than two years, I had two important papers published and a son on his way, so my wife Giorgia (also an IMP graduate!) and I decided we wanted to come back to Europe to stay closer to our families. I was also starting to feel a bad wind of political change and wanted out, to be honest.

I was still very junior - a bit more than two years' experience as a postdoc - so I was actually looking for independent fellow positions but I soon found myself competing for actual PI positions. I tried in Vienna, I tried in Lisbon, I tried all over Europe, then eventually landed in London. 2009 was the apex of the recession and securing an academic job was not easy that year, it took quite a bit of mental effort. I was lucky and particularly lucky to end up at Imperial.

Your affiliation with Imperial College involves training a young generation of scientists and 'injecting passion and wonder'. How important is teaching for you?

I take students' growth very seriously - just as seriously as I take my research. But I would lie if I said I enjoy teaching. I don't. It's not for me. Instead, I find I can be of better service to the students by organising their teaching rather than delivering it, so most of my interaction with them happens as the Director of a Master course.

I lead the largest and more challenging Master course in my Department which allows me to be more a mentor than a teacher. Rather than explaining to students what a neuron is and how it works, I can actually guide them while they write a "news & views" on a bioRxiv preprint on immunology, or hopefully help them as they search for their internal vocation. It is a way for me to have a more profound impact and, at the same time, to rethink what University is really for. This is all probably driven by the fact that, as a student, I was not attending lectures myself so now that I can move a few strings, I am simply trying to build for my students the environment I wish I had.

You also explain your research to a broader audience, for instance via TED talks or podcasts, and you share your thoughts in a blog. These outreach activities are rather time consuming - what is your motivation?

My motivation is twofold: on one hand, the moral duty of attracting children and students to science and to educate the public on the power of invertebrate research and reductionism. On the other hand, it is the sheer egoistic realisation that whenever I have the chance to simplify my research, my own understanding grows. Having to explain my work to a broader audience means I need to focus on the important issues, so that everyone can understand why we do what we do.

I pledge to write my grants and papers in the same way and while some reviewers occasionally call that "patronising", I still think it is the only way to communicate. Nothing worse than hiding one's science behind a veil of unnecessary complexity. Unfortunately, that is all too common in neuroscience. Being able to communicate to a larger audience is something I have actually learned from the IMP's Monday seminars - Kim Nasmyth famously used to say that if you cannot explain your project to your grandmother then your project is not important. I agree, and now I make that quote my own (only, I replace grandmother with grandfather...).

What are you and your team working on right now and what are your plans for the future?

Sleep has been a field dominated by mammalian research for the past 100 years, and while this has been successful for some aspects, it has led nowhere on others:  we still don't know what sleep is for, why is it so evolutionary conserved, and what happens to our cells when we sleep - which are the three fundamental questions, if you ask me. Flies give us the chance to finally address those aspects, looking from a different point of view.

Because the field was so new when I joined, I dedicated a great amount of energy to building the new tools that I needed to get started in the proper way. And that is not just because I have fun doing that; Sydney Brenner rightly said that "Progress in science depends on new techniques, new discoveries, and new ideas, probably in that order".We are now at that phase where we make new discoveries and push forward new ideas, and it is great fun.

The main hypothesis I am pushing forward at the moment is that sleep is not a unicum, but a mixed biological process addressing three different functions: it has a (small) "vital" and evolutionarily conserved component addressing some mysterious cell-biological function; a "useful" component addressing species-specific needs; a third "accessory" and larger component that is simply there to keep us out of trouble. The third component conveniently explains why a bat sleeps 21 hours while an elephant for 2 hours. We are testing this hypothesis by working on all three components.

Interview by Heidi Hurtl, 2020.