Maëla Paul, doctoral student in developmental neurobiology

What is developmental neurobiology ?

This science brings together two main areas: neuroscience and developmental biology. Researchers try to understand how the nervous system develops. The period from the embryonic stage to young adulthood is a crucial one. Today, we know that an error in this program can be the cause of neurodevelopmental disorders, some of which only appear in adulthood.
The brain is, I think, the most interesting organ of the body because it remains the most mysterious. In 2021, there's still a lot we don't understand about it. Before, we were very limited in terms of the tools we had to study the brain, but now we're in the midst of a technological boom that has led to many discoveries, even if there's still a lot to explore.
Within this vast field of research, I'm more interested in how neurons connect to each other during brain development.

How did you get into this discipline ?

Initially, I wanted to become a veterinary surgeon. After my scientific baccalaureate, I went on to study biology at the University of Paris-Saclay, where I did two years of undergraduate studies. One of my tutors told me about an opportunity to enter the École Normale Supérieure (ENS) after my second year. I didn't think my level was sufficient for the school's requirements, but I applied anyway and was accepted. I spent three superb years there. During my master's degree 1, I did a six-month internship in developmental neurobiology in a large laboratory in New York, at Columbia University. It was an exceptional experience, and reinforced my decision to do a master's degree 2 and a thesis in this field.

What's your working environment like at ?

I work in a laboratory on a human scale. I prefer this configuration to a huge laboratory, as it enables me to maintain a special relationship with my thesis supervisor, who knows how to make himself available : this is invaluable for a researcher just starting out. My thesis supervisor, Fekrije Selimi, is also the laboratory director. In fact, today there are more and more female research directors, unlike twenty years ago. This has been a great motivator for me : as a woman, we have a lot of self-censorship, we tell ourselves that we're not capable or that we're not among the best, whereas all we need is someone to believe in us.
There are three PhD students in the laboratory working on related themes. For my thesis, I'm working in a trio with a research engineer and a design engineer, because we have a very ambitious project. It's quite comfortable for me to have this technical and scientific support, it's a chance for a PhD student to be able to work on a group project, to have varied interactions, to confront ideas... It's what makes research projects progress !

What is your research topic ?

I'm working on the brain, and more specifically on the cerebellum, a structure at the back of the skull, just above the nape of the neck, which is important for fine motor skills. For example, if you can precisely touch the tip of your nose or walk upright, it's thanks to the cerebellum. The more research we do, the more we realize that the cerebellum is also involved in cognitive processes such as language and comprehension. So it's hardly surprising that it has been linked to diseases such as autism and schizophrenia. In these illnesses, it is now recognized that neurons connect poorly with each other. To determine the origin of these poor connections, we must first understand what underlies the good connections. It's in this context that I'm interested in one cerebellum neuron in particular, the Purkinje cell. It receives connections from two other families of neurons, the inferior olive neurons and the grain cells. These two types of neuron will connect to the Purkinje cell, each in its own territory. This pattern will be found in any healthy brain and for all Purkinje cells.

How are these connections established among the hundred billion neurons ?

This is the question I'm trying to answer in the course of my thesis. So far, I've identified a number of genes that may be involved in recognition between the two families of neurons I'm interested in and their target, the Purkinje cell. I'm now working on removing these genes from the genome of these neurons specifically. To do this, I'm using the revolutionary CRISPR-Cas9 technique, whose inventors were awarded the Nobel Prize in 2020. Thanks to the CRISPR-Cas9 enzyme, which can be compared to genetic scissors, we can precisely cut out portions of DNA and thus remove genes that seem interesting to us. This then enables me to study whether, in the absence of these genes, the two families of neurons connect correctly or not to the Purkinje cell. If the neurons don't connect properly, the gene is important; if they don't, it's not.

Microscopic image of a Purkinje cell turned green by the expression of a fluorescent protein (GFP). The olivary neurons have been marked in red and innervate the Purkinje cell by establishing points of contact, the synapses.

In practical terms, what is your life like as a researcher ?

My days in the laboratory are very different from one another. My experiments are very varied, no two are alike, although some can last up to two months, which requires a little patience !
Research is always tedious: some techniques take several months, even years, before they work, and then you have to repeat the manipulations several times to be sure of their validity.
At the Collège de France, we have a number of platforms to support us, notably the imaging platform. Thanks to the latter, we have access to a wide range of microscopes and a team of talented physicists who provide real technical support. Apart from that, I'm a member of the ChADoC association (Chercheurs Associés et Doctorants du Collège de France). We talk about science in general, but also about our daily lives in the lab. It's great to be able to talk together, to put failures into perspective and celebrate successes !

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Maëla Paul works at CIRB, in the Mice, Molecules and Synaptogenesis team headed by Fekrije Selimi. Her thesis is entitled " Characterization of the presynaptic molecular identity of the climbing fiber ".

Photos © Patrick Imbert
Interview by Océane Alouda