BSDB Beddington medal winner 2018
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I am a young developmental neurobiologist and, over the years, I have become conscious that motivation, passion and drive are key for anyone planning on doing academic research. Everything else – like dedication or perseverance – will naturally come with it.
I did my undergraduate studies (a BS in Biology and a MS in Neurobiology) in Italy at the Sapienza University of Rome. As a BS student, I joined the laboratory of Sergio Nasi at the Institute of Molecular Biology and Pathology (CNR, Rome) and I ended up being hooked by a project on cancer biology. Despite continuing to think of myself as a future neuroscientist, working on brain tumors was so challenging and motivating that I decided to remain in the same laboratory for my Master’s project. By discovering that mitotic death was a novel aspect of Myc proliferative biology, I made an important contribution to the effectiveness of Myc inhibition as a potential therapy against glioblastoma multiforme.
I deeply value the three years I spent as an undergraduate in the Nasi lab. The findings of both my BS and MS projects were included in two publications and I had gained a broad hands-on experience in cellular and molecular biology. Most importantly, those years showed me what doing research actually means. I discovered that I enjoyed the day-to-day process of research, from designing experiments and analyzing data to problem solving, listening to seminars and sharing my acquired knowledge with others. I also loved the process of writing papers and going to conferences. I learned that results are the consequence of not only hard work and organization, but also innovation, originality and a great capability to turn failures into a tool to increase our understanding.
I was a successful student, but before actually doing research, I had no idea whether or not I had the necessary emotional and intellectual attributes that research requires. During those years, I discovered that doing research made me happy. The PhD is an amazing but intense journey. I think that some research experience before starting the PhD is invaluable. An excellent alternative to what I did is to work as a research assistant for about a year, as many people do. This is a smart idea and a great opportunity.
In 2011, I started my PhD in Neuroscience at the Institute of Neuroscience of Alicante in Spain. I joined the laboratory of Beatriz Rico to work on cortical inhibitory circuit development. Later, I moved with the lab to King’s College London where I spent three years at the Department for Developmental Neurobiology and completed my PhD work.
The first project I worked on during my PhD aimed at understanding the molecular code that underlies inhibitory synapse specificity. This was an ambitious and challenging project. It was, however, also extremely exciting, as understanding how neuronal connections are established and organized in functional networks during development is critical to understand brain function. We revealed the transcriptional dynamics of different cortical interneurons during brain wiring and identified subtype-enriched synaptic molecules. I was very lucky to team up with two very talented postdoctoral researchers in the lab who joined the project at different stages. Together, we showed that the connectivity of different interneurons relies on the expression of these subtype-specific synaptic genes. However, the most important finding of this project was that these selective molecular programs emerging during development in cortical interneurons not only support their early wiring but critically underlie inhibitory circuit specificity. This first project was focused on different interneuron types but we know that, after their integration into canonical circuits, activity-dependent plasticity endows neurons with the flexibility required for adapting to sensory experience. Parvalbumin (PV+) cells – a subtype of interneurons – are an excellent example of this plasticity. They can exist in different states and change their properties in response to changes in activity. In the second project I worked on during my PhD, we uncovered a cell-specific molecular program through which a perineuronal net protein dynamically gates PV+ interneuron function. In particular, we showed that the perineuronal net protein Brevican dynamically regulates the excitatory inputs and firing properties of PV+ interneurons both during development and upon experience-dependent plasticity. We also revealed the molecular mechanisms by which this happens and showed that such dynamic program is required for normal cognitive function. We are now writing a manuscript with the results of the first project, whereas the findings about how Brevican gates PV+ cells were published last year in Neuron. Being awarded the 2018 Beddington medal for the best PhD thesis in developmental biology felt like the summit of my PhD. Rosa Beddington is one of my scientific heroes and it was a true humbling honour to receive the medal.
Figure caption: The perineuronal net protein Brevican (in red) surrounds parvalbumin interneurons (cyan) in the hippocampus.
Overall, my PhD has been an amazing experience. I was very lucky to work on questions I was passionate about. It tempered the frustration of any failure and kept me going while amplifying the ‘adrenaline rushes’ and the profound happiness of any accomplishment.
I also believe that building a balanced relationship with your supervisor is critical. Beatriz gave me the right amount of guide and support, but also patience, trust and intellectual freedom. I think that supervisors who are able to provide a balanced mentoring can really foster the growth of young scientists.
Another important consideration is that nowadays science is increasingly collaborative. I would not have accomplished the same things had it not been for the ‘support network’ around me. During my PhD, I was fortunate to have the chance to build and participate in collaborations with researchers both inside and outside our lab. I urge future PhD student to seek labs with a collaborative and pleasant environment.
Another aspect that I found to be important for a young researcher’s career is having the possibility to build a network outside your lab or department. Apart from being an excellent opportunity to get feedback on your work and get to know the most recent scientific discoveries, conferences are the perfect chance to do networking. Students and postdocs you meet today may be your fellow PIs or collaborators of tomorrow. It can be intense and at times tiring but it is an important part of the work. As such, it should not be underestimated or overlooked. Conferences can also be a great inspiration for the nearest next career steps. For example, after one specific talk at a Gordon Conference I attended towards the end of my PhD, I had an epiphany about what I wanted to do in my postdoc. Another conference (the Axon Guidance meeting in Cold Spring Harbor) is actually where I first met my present supervisor, Gord Fishell. I am now a postdoc in Gord’s lab at Harvard Medical School and at the Broad Institute.
On this subject, a question I am often asked is if it was difficult to find my postdoc position. It may appear as a recurrent theme, but again, I do believe that passion and motivation are key. Increased knowledge often means increased awareness of what we do not know. As I approached the next step in my scientific career, I realized I had more questions than when I started. I thought about the questions I was more passionate about and wrote a project proposal. I then sent my draft to very few selected labs that had the tools or the knowledge to develop such a project and explained why I was interested. I got great feedback from all of them. This is just an example to say that looking for what really engages you is also a way to, in turn, engage your interlocutor.
One thing I learned so far is that doing research is not a sprint, is more like a marathon. You do not want to wear uncomfortable shoes, i.e. choose a question that inspires you. You can have an hypothesis to test but no bias or preconception. Do not try to force the results to fit the hypothesis, keep an open mind. Yet, you also have to be patient and persistent. Like in a marathon, indeed. One day the muddled results you have been having for a long time will start having a shape. It will be a turning point. You will see that you have discovered something and that you can start telling a story. That realization will be one of the best moments of your career.
As for me, I have just started a new run. Contributing to the common endeavor of trying to understand brain development is a privilege and I wish to do it for as long as I can.