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PSL: The PSL/Biogen program was launched in 2018. Can you briefly describe the primary aims behind the collaboration?

Antoine Triller: The PSL/Biogen program is fairly unique. To start with, it’s undoubtedly the first exchange program to forge an institutional relationship between a company such as Biogen and a university, and yet it’s different from other programs that fund dissertation research, such as the CIFRE program. What’s unique is that the doctoral candidates taking part in the program receive double mentoring from PSL researchers and scientists at Biogen, so they’re introduced to two different cultures. The PhD candidates from PSL – those on what we might call a conventional academic track – work alongside Biogen researchers or engineers who have opted to expand their professional activity by doing a PhD. That mingling of two different cultures is genuinely motivating, and it could be extended to other instructional programs, even at the Master’s level.
Chris Henderson: This convergence between PSL and Biogen is really significant, and in order to explain it I should perhaps start by describing what our partnership isn’t! To address one common misconception: it’s not a way for Biogen to fund scientific research that we would like to see happen. We have other, much more direct ways of doing that. Instead, the value of this doctoral program is that it allows for and even promotes a bridge between two different worlds that often tend to be at loggerheads with each other. Our hope is that this scientific interaction will help give rise to a cohort of researchers who aren’t afraid to create partnerships and indeed will be able to capitalize on them. If, on top of that, the program leads to great science and great discoveries for patients, naturally we’ll be overjoyed.

PSL: This is the first partnership that Biogen has signed with a French university. Why did you choose PSL?

C. Henderson: Indeed, it’s the first agreement Biogen has signed with any university in Europe. Our decision was guided first and foremost by the excellence of PSL’s laboratories and educational programs. We were already familiar with the quality of PSL, because several of us at Biogen had met or worked with PSL researchers in the past. We were also very intrigued by the multidisciplinary aspect of PSL, and the presentations we viewed at this first symposium have really cemented our belief that we made the right decision. The students seem to be taking full advantage of the opportunities for interaction with the engineering labs, the chemistry labs and so on. The initial results have been very positive and encouraging for the future.
A. Triller: We should also highlight the warm and positive reception from PSL’s partner universities around Paris. Their doctoral schools are hosting most of the PhD candidates in the program and those schools have embraced this partnership. The agreement with PSL has also given Biogen a chance to work with those partner institutions.

PSL: What can you tell us about the eight doctoral candidates chosen for the program? What are their topics of research?

A. Triller: Their research encompasses a fairly wide array of topics, ranging from neuroscience to imaging, quantitative biology and chemistry. What they all have in common is their desire to shed new light on the mechanisms behind neurodegenerative diseases such as Alzheimer’s, Parkinson’s, multiple sclerosis and so on. In terms of their profiles, they’re all very committed to the goal of the program, which is to combine students from standard academic curricula with students who may have followed a more heterodox path. In my mind that’s really an essential point. The PSL/Biogen program offers proof, if any were needed, that a mix of students from different backgrounds is valuable to both researchers from basic research labs and scientists working in contact with hospital patients. It’s a sign of Biogen’s strength and its smarts that they realized what a unique and potentially rewarding asset this would be.
C. Henderson: The eight dissertations in the program really do cover an exceptionally wide range of topics. Some of the students are exploring areas of basic research, like the work being carried out by Anna Nawrocka, under the direction of Alena Shkumatava (Institut Curie) and Jessica Hurt (Biogen) on the RNA of zebrafish, for her dissertation on “Regulation of neural stem cells and neurogeneration by long noncoding RNAS.” Another example is Clémentine Hatton, working under the direction of Stéphane Dieudonné, Vincent Villette (Institute of Biology at Ecole Normale Supérieure - PSL) and Yael Mandelbat-Cerf (Biogen), who’s researching the electrophysiology of Purkinje cells for her dissertation, “Dentritic calcium signaling and activity of cerebellar Purkinje cells in vivo.” That basic research will be instrumental in two very important topics for future drug discovery: improving our understanding of non-coding RNA, and calcium signaling.
A. Triller: In addition, I think it’s important to mention some of the applied research, such as the work of Benoît Beliard (a doctoral candidate at ESPCI Paris, a PSL member school) and John Joyce (a Biogen research engineer), both of whom are extremely promising in their fields. Benoit is working on a high-definition ultrasound imaging program, under the supervision of Sophie Pezet (ESPCI Paris) and Daniel Bradley (Biogen), among others. That research has attracted a lot of interest in the scientific community. Specifically, his dissertation topic is “Use of functional ultrasound imaging in a pre-clinical animal model of multiple sclerosis: new insight in the alterations in the brain.” John, meanwhile, is working under the direction of Morwena Latouche and Giovanni Stevanin at EPHE - PSL along with Anthone Dunah and Will Chen at Biogen on a study entitled “Progranulin deficiency in frontotemporal dementia induces a significant burden upon inhibitory interneurons.”

PSL: What do you see as the major challenges facing neuroscience in the years to come?

C. Henderson: In my opinion, the number one challenge we face is undoubtedly gaining a better understanding of the human nervous system. Currently, despite the wonderful science that’s been conducted at the experimental level, we’re still uncertain about the effects on humans. Diseases have multiple and complex causes; in order to design treatments, it’s absolutely critical that we understand the complexity of the phenotypes.
A. Triller: From the standpoint of the basic sciences, the challenge in my view involves the major leap in scale from a very basic molecular mechanism to a cell-level phenomenon, which then in turn is incorporated into neural networks and so on. Those leaps in scale are even more complex when you take into account the regulatory activity that happens at each level, which then governs all the other levels. It all adds up to a non-equilibrium, non-stationary system that’s very difficult to model. When you apply this set of issues to a mutation that causes, say, Alzheimer’s Disease, you’re ultimately seeking to determine where and when therapeutic intervention is appropriate.

PSL: The program’s 2020 Call for Proposals is due to be issued shortly. Can you say a few words about that?

A. Triller: As in previous years, the proposed dissertation topics need to come under the general umbrella of the neurosciences, including deep learning and the data sciences, and have potential implications for neurodegenerative, demyelinating and genetic diseases. Any scientific approach will be considered: molecular, cellular, in vivo/in vitro, in animals or humans. The projects can lie at the interface between the neurosciences, including the cognitive sciences, and other disciplines such as physics, chemistry, information technology, mathematics and nanotechnology.