Insights N°2 - EN

INSIGHTS

The magazine of IdEx Université Côte d’Azur• No. 2 - December 2024

Feature NEUROSCIENCE

Spotlight on the Academies of Excellence

Profiles: Jérôme DELOTTE Christian PRADIER

All the projects presented in this magazine have been supported by the French government through the France 2030 Investment Plan managed by the National Research Agency (ANR), as part of the Initiative of Excellence Université Côte d’Azur under reference number ANR-15-IDEX-01.

Université Côte d’Azur

This second issue of Insights explores the rich and diverse research in neuroscience carried out in the laboratories of the Université Côte d’Azur community. Through the experiences shared by different researchers, you will gain a deeper appreciation for the fundamental approaches at the heart of our understanding of complex biological phenomena. These phenomena often find their roots in properly or poorly functioning ion channels, a historical theme for the university and a strategic one for the IdEx. These discoveries also lead to therapeutic applications in a variety of pathologies and are helping us understand their origin. A few incorrectly adjusted proteins, for example, can cause functional disorders with potentially serious neurological, sensory and cognitive repercussions.

The other sections deal with education, research, innovation and international development, and share the latest news from our academies of excellence.

We hope you enjoy reading this magazine and look forward to hearing your feedback at insights@univ-cotedazur.fr

FROM THE EDITOR CONTENTS

PITCH CHALLENGE

Publisher: Université Côte d’Azur – 28 av. de Valrose 06000 Nice

Legal representative: Jeanick BRISSWALTER, President, Université Côte d’Azur

Sylvain ANTONIOTTI, Vice-President Initiative of Excellence (IdEx)

Publication Director: Sylvain ANTONIOTTI, Vice-President, Initiative of Excellence (IdEx) Université Côte d’Azur

Editorial Committee:

Diana SEBBAR, IdEx Executive Director Saranne COMEL, Operations Director, IdEx Europe and International Program

Aurélie DELORT, Operations Director, IdEx Education Program

Contributors: Academies of Excellence, Université Côte d’Azur scientific community

Sébastien BIEHLER, Operations Director, IdEx Innovation Program

Coordination: Céline PACCOUD, Communication Manager for Major Projects, Head of Communication & Branding

Design: Jeremiah TURRINI, Graphic Designer, Communication & Branding Department

Printing: University Digital Production Center

Publication date: December 2024

ISSN in progress

Yasser MAGHRBI, Operations Director, IdEx Research Program

PITCH CHALLENGE

The Pitch Challenge, a dynamic section covering the careers and/or projects of inspiring individuals who belong or have belonged to the Université Côte d’Azur community.

Dr Michal BALAZIA

Michal Balazia holds a PhD in computer science, is a permanent researcher (ISFP) at the Inria center of Université Côte d’Azur and a recipient of the IdEx “Fellowship for Young Researchers” and IdEx “Attractivity Package.”

Artificial intelligence for the diagnosis of psychiatric disorders

Since most of my studies focused on cryptography and video surveillance, I never imagined applying my IT skills to a field other than security. However, as these issues raised more and more concerns about “Big Brother” conspiracies, and I noticed direct military applications in countries that repress human rights, I began to consider another nobler goal. I noticed that there was a great need for innovation in medicine. This is particularly true in psychiatry, where psychiatrists keep virtually no patient records to protect their privacy. Compared to doctors in other disciplines, their working methods could be considerably improved by digital technology in general and artificial intelligence in particular. After completing a PhD at Masaryk University in the Czech Republic where I defended my thesis

in 2018, and a first postdoctoral fellowship at the University of South Florida, I was hired at Inria as a postdoctoral fellow thanks to an IdEx postdoctoral grant. This attractivity grant offers PhD students and young researchers, often from abroad, the opportunity to carry out their research in France. In 2019, the program was called “Thematic Postdoctoral Contract”. The topic I suggested was the development of AI models for the automated analysis of facial expressions and gestures used for digital health monitoring. The project was aimed primarily at Alzheimer's patients, and it was associated with two of IdEx’s strategic programs: Aging and Digital Health. It was an excellent way to become familiar with Inria and Université Côte d’Azur and to meet a wide variety of scientists. Throughout the project,

I was in contact with computer scientists from DFKI in Germany and clinicians at the Nice University Hospital and developed a close collaboration with them, notably within the Cognition & Behavior & Technology (CoBTeK) partnership headed by Professor Philippe Robert. In 2021, I was awarded a second IdEx “Fellowship for Young Researchers” postdoctoral grant, before landing a permanent Inria Starting Faculty Position (ISFP) in 2023. My current project aims to harness the power of machine perception to diagnose psychiatric disorders. In an interdisciplinary environment that combines psychiatry and explainable AI, we are attempting to identify clinical markers of aberrant behavioral patterns in human interactions based on the formal analysis of medical

data and explainable biosignals. Our clinical framework allows us to carry out an in-depth analysis of atypical behavior by detecting specific facial and body gestures such as hand movements and eye contact. We are also classifying emotions and assessing stress levels and engagement in the conversation. Clinicians will be able to interpret the combination of these digital phenotypes and establish more precise diagnoses and, hopefully, will discover new biomarkers likely to improve our understanding of mental pathologies.

On a personal level, I found it very satisfying to work with clinicians in a relationship of mutual respect knowing we share a common passion for our work. I envision my future work at this intersection between technology and medicine.

MARRES: Three trajectories and a shared mission

Camille Boucaud, Florina Jacob and Lionel Pourchier, three alumni of the MARRES program, each tell us their story and illustrate in a unique way how science, community service and innovation can contribute to marine conservation.

Camille BOUCAUD

“I’ve always been fascinated by marine biology and my adventure with MARRES was a turning point in my career.”

Born in France, I earned my master’s degree in 2023 after completing my thesis at the Marine Biological Laboratory in Woods Hole (USA), a life-changing experience. While I was there, I developed a passion for cephalopods, which are fascinating sea creatures. I am now pursuing a PhD in microbiology, genetics and immunology at Michigan State University, investigating the symbiosis between the Hawaiian bobtail squid and the bioluminescent bacterium Vibrio fischeri. My research focuses on a protein, galaxin, which could contribute to the interaction between microorganisms and their host. Using advanced genetic engineering technologies and microbiological tests, I hope to provide answers to this biological mystery. I am glad to know that the partnership with Woods Hole is still active and that other MARRES students can have the same opportunity I had to be immersed in this unique research environment.

“For me, marine conservation must go hand in hand with a deep commitment for local communities.”

Originally from Colombia and valedictorian of the class of 2021, I joined the NGO Coral Guardian as head of scientific and field projects after finishing a master’s thesis in which I analyzed the scientific and socio-economic data collected by the NGO. Today, I spend my time between France, Indonesia — where the NGO started its projects — and Spain, working hands-on in coral reef protection and restoration. My role is not limited to scientific work; it also includes the sustainable development of local communities. I help fishermen and coastal communities adopt more sustainable practices by providing them with the tools and knowledge to protect and restore their environment. This holistic approach promoted by MARRES, that combines conservation with human development, is what motivates me every day to remain committed to Coral Guardian.

Florina JACOB

Lionel POURCHIER

“MARRES helped me transform my passion for marine conservation into a concrete entrepreneurial project.”

After an initial degree in nuclear engineering, I completely changed direction after graduating from MARRES in 2020. I first co-founded Blue Leaf Conservation, but very quickly realized that the business environment was not ready for it. I went on to create EverSea, an innovative company that helps finance marine conservation projects by connecting them with private investors. EverSea uses technologies such as artificial intelligence and blockchain to scientifically assess the impact of projects on biodiversity and climate. I am particularly proud today to be able to keep on working with MARRES. I regularly supervise internships and PhD projects, which is currently the case with David Broussard, who is a PhD student in marine ecology (ECOSEAS laboratory) and economics (GREDEG laboratory). This connection with MARRES is a source of inspiration and mutual support.

Three visions and a shared ambition

We come from different backgrounds, but we share the same goal, which is to protect the oceans. Whether this is done by pushing back the frontiers of academic research, by innovating in entrepreneurship to generate concrete environmental impact, or by heading marine conservation programs on site with local communities, we firmly believe in the power of collective action.

MARRES has helped us understand that there are many ways to change the world. When our multiple trajectories intersect and complement each other, they give rise to the most sustainable and innovative solutions.

Kyrylo OSTROVSKY

Alumni of the Master of Research in Fragrances and Fine Chemistry

In the summer of 2022, as I was studying chemistry at Kharkiv National University in Ukraine, I received a message from my dean, Oleg Kalugin, telling me about an exceptional opportunity: the possibility to enroll in the Université Côte d’Azur double degree program. The master’s program in molecular chemistry, which combines training in modern experimental techniques with the study of theoretical concepts, immediately caught my attention and seemed promising. I seized the opportunity without hesitation.

Once in France, I had to deal with the language barrier. Fortunately, the professors were sensitive to my struggles, and even though all courses were previously taught in French, they agreed to teach and communicate in two languages: English and French, for which I am very grateful! This made it much easier for me to understand the course material in French and to communicate during seminars and labs. With their help, I was able to quickly assimilate the new methods in organic, analytical and physical chemistry.

The second year of the master’s program was crucial in the choice of my future path. While most students continued with the professional master’s degree (FOQUAL), I had always been drawn to research. At the beginning of my second year in the research master’s degree in fragrances and fine chemistry, I was still unsure of the specific field of chemistry I wanted to explore. One event, however, made my choice clear.

The unique opportunity was given by Université Côte d’Azur and the Udice association to be selected

to attend the 73rd annual meeting of Nobel Prize laureates in Lindau. Although the 2024 meeting was dedicated to physics, I decided to apply. This event was organized to encourage scientific exchanges between Nobel Prize winners and young researchers, and it exceeded all my expectations. It not only provided an informal setting for enriching conversations with world-renowned scientists, but it was also the opportunity to meet young researchers from all over the world. I was particularly impressed by how open the Nobel laureates were, notably Anne L’Huillier and Alain Aspect, to answer both scientific and personal questions. The advice they gave me, especially on a personal level, was extremely valuable! The experience was a turning point for me. It helped me understand what appeals the most to me in science: the intersection between chemistry and physics and between theory and practice.

As a young researcher about to embark on a PhD, I recognize the full value of the skills I acquired and the opportunities I was offered during my master’s degree at Université Côte d’Azur. These resources are essential for a fulfilling professional career and especially for work in scientific research.

PROJECTS IN THE NEWS

The Research Program of the Université Côte d’Azur Initiative of Excellence deploys a wide range of actions and measures to support research. This section features some of the ongoing or completed research projects that are contributing to the international outreach and attractiveness of Université Côte d’Azur.

A quantitative history of

the disciplinary boundaries

OF THE FRONTIERS OF ECONOMICS

Awareness has grown of the importance of interdisciplinarity in economics in light of the challenges facing society today. To deal with climate change and develop solutions that take all dimensions of the problem into account, interdisciplinary collaboration is essential between economists, engineers and natural scientists. However, the simple wish for more interdisciplinarity

is not enough to make it work and become a reality. Many factors, such as methodological differences, distinct disciplinary cultures and research evaluation systems, can be obstacles to interdisciplinary collaboration. Besides that, many interdisciplinary projects have not had the expected impact, and researchers often find it difficult to make interdisciplinary teams work harmoniously

This view of a network of bibliographic links illustrates the connections between articles from different disciplines, based on their shared citations. It is used to map the fields where economics shares topics and methods with psychology and neuroscience.

together. As regards economics, the discipline has long had the reputation of being isolated from other disciplines, and especially from other social sciences, which makes interdisciplinary projects in economics all the more difficult. Recent surveys show, for example, that 57% of economists do not agree that interdisciplinary approaches are more valuable than mono-disciplinary ones.

Our research project is a historical study of interdisciplinary relations in economics, and its first objective is to identify historical changes in interdisciplinary practices in economics. We are using quantitative tools to approximate the relationship between economics and other disciplines. By measuring trends in citations between disciplines, for example, we are studying how scientific practices have been changing and are comparing the relationship between economics and other disciplines.

A second aim of the project is to use specific cases to examine the factors that have contributed to the success or failure of past interdisciplinary efforts in economics. This approach allows us to identify strategies for effective collaboration and will teach us how to navigate the complexities of today’s interdisciplinary research. We might assume that interdisciplinary collaborations are primarily influenced by questions of scientific interest and quality, but history shows that social and organizational issues are just as important when it comes to bringing several disciplines together.

Alexandre TRUC CNRS researcher, Research Group in Law, Economics, and Management (GREDEG)

EDUCATION RESEARCH INNOVATION

EXCEPTIONAL VENUES

Trotabas Campus - Main hallway - Component Institution of Université Côte d’Azur

LIGHT AND COLD ATOMS: towards a single-photon source

Light scattered by a quantum emitter can exhibit properties that cannot be interpreted by classical physics, most notably measurements of temporal intensity correlations. In classical physics, this measuring technique involves quantifying the degree of coherence or “similarity” of light intensity fluctuations at different times. It was first used in space by Hanbury Brown and Twiss in the 1950s and 1960s to measure the diameter of stars.

In quantum optics, temporal intensity correlations are expressed in terms of correlations of the number of photons, the elementary particles that make up light. A phenomenon that is specific to quantum optics, and therefore impossible to explain by classical physics, is photon antibunching. This refers to perfect anti-correlation with zero delay, indicating that the emitter is emitting only one photon at a time. This is known as a single-photon source.

Single-photon sources are now at the heart of numerous applications in quantum technologies, such as quantum communication and cryptography, quantum simulation and metrology. Numerous platforms are already available to deliver this type of source. Certain experimental set-ups, for example those based on four-wave mixing, are used to obtain high-brightness sources (i.e., that deliver a large number of single photons per unit time). However, the spectral widths of these sources are generally too large for some applications, such as quantum memory. Quantum emitters such as NV centers or quantum dots are good alternatives and are becoming increasingly popular. But these sources are expensive to manufacture and generally require a special environment, such as cryogenic temperatures.

The aim of the project developed at INPHYNI is to produce a single-photon source that combines the advantages listed above, using an existing, well-established platform. For this, cold atoms are particularly suitable candidates. The choice of atomic resonance provides a narrow, extremely well-controlled spectral width. We also know how to trap a large number of atoms, on the order of a billion or more, thus potentially ensuring a very bright source of single photons. Finally, the temperature of these atoms is of the order of a hundred microkelvin, that is, close to absolute zero, which reduces the impact of atomic motion.

The challenge now is to be able to observe photon antibunching when the number of emitters is large. This effect is usually observed for a single quantum emitter and disappears for a large number of atoms. To this end, we are working in collaboration with a German research group led by Arno Rauschenbeutel (Humboldt University, Berlin), who recently demonstrated photon antibunching in an experimental configuration that makes use of interference effects. However, the experiment in Germany requires a complex set-up to implement. The experiment carried out at INPHYNI should

demonstrate the feasibility of a single-photon source with a much simpler system, an essential step towards a potentially marketable system.

Mathilde HUGBART

CNRS Senior Researcher at the Nice Institute of Physics (INPHYNI)

Light scattered by a cloud of cold atoms (in red in the center of the image) trapped in a magneto-optical trap at the Nice Institute of Physics.

OPTICAL METASURFACES

Optics plays a major role in many modern technologies. For example, the Internet is based on a network of optical fibers in which information travels, encoded in the form of light. Imaging techniques, whether with microscopes that image the smallest distances or telescopes that image the infinitely large, rely on the use of optical components. These enable light to be controlled and shaped. For example, lenses focus light, polarizers control its polarization (i.e., the direction of the electric field) and spectral filters control its wavelength. In this context, there is a need to develop thinner, lighter optical components that will be easier to integrate, but also capable of ensuring better control of the properties of the light. Metasurfaces, which appeared some fifteen years ago, are an interesting approach to producing ultra-thin optical components. Metasurfaces are two-dimensional arrays of structures with sizes smaller than the wavelength of light (of the order of a hundred nanometers for visible light) separated by distances also smaller than the wavelength of light.

By varying the size and shape of each nanostructure in the array, we can locally control the properties of the light, for example, to deflect it at a positiondependent angle and focus it like a lens. The aim of this article is to explain how metasurfaces work as well as their applications.

Conventional optical components such as lenses and prisms rely on refraction, which is the deflection of light at the interface between two media with different optical properties. The angle of refraction depends on the angle of incidence of the light and the refractive indices of the initial n1 and final n2 media. The angle is predicted using the Snell-Descartes law: . This principle explains how the angle of deflection of a prism depends on its refractive index, or how the curvature of a lens surface focuses light.

Adding a metasurface at the interface between these two media is equivalent to introducing an

additional phase . This phase term simply reflects the fact that the metasurface introduces an additional time delay. Moreover, this phase depends on the geometry of the nanostructures (size, shape, etc.) that make up the metasurface. By spatially varying the metasurface nanostructures, we can introduce a position-dependent phase, . The laws of refraction must be modified to take into account the effect of this phase, . If the phase is varied in the x direction only, it has been shown that the SnellDescartes laws should take the following form:1

being considered for the manufacture of large-scale metasurfaces.

Figure 1A illustrates the concept of a metasurface. The first step is to identify the phase profile associated with the desired optical function (in this case, a lens). We then discretize into phase pixels. Each phase pixel corresponds to a nanostructure on the metasurface. Numerical simulations are then required to identify the geometry of the nanostructures needed to produce the desired phase for each pixel. This makes it possible to produce lenses that are completely flat, as shown in Figure 1D.

To manufacture such metasurfaces in the laboratory, electron lithography is generally used to draw the necessary patterns with nanometer resolution. Manufacturing then involves a number of steps to etch these patterns into a thin layer. However, electron lithography-based manufacturing is expensive and difficult to deploy on a large scale. To overcome this, an option is deep ultraviolet optical lithography, which is already used to manufacture computer chips. Nanoimprinting methods are also

The applications targeted by the metasurface team at the Research Center for Heteroepitaxy and its Applications (CRHEA) are diverse. For example, it is developing metasurfaces for faster LIDAR rangesensing systems.2 It has developed metasurfaces to control laser emission and make it more directional.3 The team is working on improving the sensitivity of detectors using metasurfaces that focus light at the center of each pixel. As shown in Figure 1C, the team is developing metasurfaces that generate holograms4 which could have applications in augmented reality systems.

(A) Electron microscope image of nanostructures on a metasurface. (B) Schematic representation of the approach used to create metasurfaces (adapted from 5). (C) Photo of a centimeter-sized metalens. (D) Views at different scales (left) of a metasurface that produces the hologram on the right (adapted from 4).

Rémi COLOM

CNRS Researcher at the Research Center for Heteroepitaxy and its Applications (CRHEA)

1Yu, Nanfang, et al. “Light propagation with phase discontinuities: generalized laws of reflection and refraction.” Science 334.6054 (2011): 333-337.

2Juliano Martins, Renato, et al. “Metasurface-enhanced light detection and ranging technology.” Nature Communications 13.1 (2022): 5724.

3Xie, Yi-Yang, et al. “Metasurface-integrated vertical cavity surface-emitting lasers for programmable directional lasing emissions.” Nature Nanotechnology 15.2 (2020): 125-130.

4Song, Qinghua, et al. “Printing polarization and phase at the optical diffraction limit: near-and far-field optical encryption.” Nanophotonics 10.1 (2020): 697-704. 5Mikheeva, Elena. Design, fabrication and characterization of dielectric optical metasurfaces. Thesis, Aix-Marseille, 2020.

COOKING AND EATING AT THE END OF THE PREHISTORIC PERIOD IN THE MEDITERRANEAN

While humans were hunter-gatherers for most of prehistoric times, the Neolithic period was a major turning point in the history of food. During this period that lasted from the sixth to the third millennium BC in Europe, agriculture and animal husbandry were introduced and a new type of vessel was used: ceramic pots. The earliest Neolithic settlements in Western Europe were located in southern France and Liguria, where cereal cultivation and goat and sheep herding mainly developed.

This research project explores the largely unknown food and cooking habits of these early farmerbreeders in southern France, Liguria, Corsica and Sardinia.

The main object of study is pottery. Used for many culinary functions, it has porous properties and thus absorbs some of the contents. The molecules of Neolithic foods trapped in the pot surface have been partly protected from degradation for millennia. They can be extracted and identified using appropriate chemical methods.

One of the aspects of this research is to combine these chemical data with the shape of the vessels, their volume, traces of wear on the surface and

information from other archeological remains (bones, seeds, etc.). This information can be used to identify the products eaten by Neolithic populations, such as dairy products, oils, cereals, etc. The next step is to characterize the various processing methods (cooking, filtration, fermentation, etc.). In the longer term, these data will be valuable to determine the structure of the food system and better understand the social organization of Neolithic groups: how food was prepared and eaten on a domestic or collective scale, how products were transported and exchanged, seasonality of use, and so on.

Léa DRIEU CNRS researcher at the Culture and Environment, Prehistory, Antiquity and the Middle Ages laboratory (CEPAM)

Molecule extraction from ceramic powder

Data interpretation Gas chromatography and mass spectometry analyses

NEURO SCIENCE SCIENCE FEATURE

NEUROSCIENCE

Feeling, thinking, and acting, as well as communicating, memorizing, solving problems, finding our bearings in space, imagining the future and planning strategies — these are just some of the feats our nervous system is capable of, led by its conductor, the brain. Based on an interconnected set of nerve cells — neurons — that communicate with each other via electrical signals, the nervous system still holds many mysteries that scientific research is trying to unravel. Our nervous system in general, and our brain in particular, is of great interest to many research teams at Université Côte d’Azur, in terms of its development and maturation, its functioning, its dysfunctions and the diseases that plague it. Here is a brief, nonexhaustive overview of some of the leading work being done by Côte d’Azur researchers.

SENSING THE WORLD

Sight, hearing, smell, taste, touch — our five senses are our gateways to the world around us. We use these senses to perceive and understand our environment in order to adapt to it. To receive stimuli from the external environment, our body has specific sensory receptors for each sense. In this respect, “the sense of smell has a number of particularities,” says Jérémie Topin, a chemist at the Nice Institute of Chemistry (ICN) whose research is focused on better understanding the mechanisms of olfaction. “Smell is not measurable in itself, it’s not a quantity that can be determined like the wavelength of a light source or the frequency of a sound. Through the sense of smell, our brain is actually interpreting the physico-chemical properties of molecules. Our ability to smell odors is therefore a complex cognitive process.” When odorant molecules pass through the nasal passage to reach the olfactory epithelium,

NEUROSCIENCE

they are solubilized in a mucus in which neurons with olfactory receptors are immersed. In humans, “there are almost 400 types of olfactory receptors that are activated in specific ways depending on the chemical features of the odorant molecules,” continues the chemist. Once activated, the nerve cells associated with these receptors transmit this information via a nerve signal to the olfactory bulb. This nerve impulse is then relayed to different areas of the brain, which interpret the information as odors according to a “combinatorial code.”

“An odorant molecule may have various chemical features recognized by different receptors, and one type of receptor is likely to be activated by different volatile compounds with the same chemical feature. Recognizing a scent is like playing a musical score with 400 available notes,” says Jérémie Topin.

According to some studies, this combinatorial code enables us to distinguish between several hundred billion different smells.

But this combinatorial code is only known for a few odorant molecules. To remedy this, the chemist is working with his team and partners at the NeuroMod Institute to create a “computational” nose that could determine this combinatorial code for all odorants.

“This would make it possible to predict the smell of molecules without having to smell them,” says Jérémie Topin. To this end, these researchers have already created the first database of associations between odorant molecules and olfactory receptors. This database, called M2OR, brings together data from the scientific literature on more than 50,000 such associations, and is available online (https:// m2or.chemsensim. fr). Today they are working on

developing artificial intelligence models that predict which receptors will be activated by a molecule so that, ultimately, its smell can be determined digitally. These data may be useful in perfumery and in selecting food flavors, as well as in mental health. “Smells trigger emotions because the smell center is connected to the brain areas that manage emotions,” explains Renaud David, a psychiatrist at Nice University Hospital and specialist in sensory disorders in the elderly. It is therefore possible, to a certain extent, to modulate our emotions with scents, and therefore to use them as non-medicinal care to improve the daily lives of some patients. “Some scents, such as lavender or lemon balm, have a soothing effect. Used in nursing homes, they help reduce agitation, anxiety and sleep disorders in the elderly. Others, such as citronella, have a stimulating effect that helps motivate apathetic patients,” explains the psychiatrist. Through their collaboration with NeuroMod, these researchers hope to develop psychophysiological scent blends that amplify these relaxing or stimulating effects.

STATE-OF-THE-ART TEACHING

At Université Côte d’Azur, neuroscience is not just a field for research. It also features prominently in our teaching, and several masters programs are dedicated to the field. The latest addition, the Master of Neuroscience, was created in 2024 and comprises two courses entitled “Cellular and Integrated Neuroscience” and “EuroMediterranean Master of Neuroscience.” A third joint degree course with the University of Seville will begin in 2025. This course, co-directed by three teacher-researchers at the Sophia-Antipolis Institute of Molecular and Cellular Pharmacology, Jacques Barik, Ingrid Bethus and Jacques Noël, aims to give students solid skills in fundamental neuroscience and equip them for clinical applications. “Since its inception, this master’s program has been flourishing, raising Université Côte d’Azur’s profile,” says Jacques Barik. Two other masters programs also have a neuroscience component. The first, “Modeling for neuronal and cognitive systems,” is an international Master of Science (MSc) taught in English and coordinated by Ingrid Bethus and Patricia Reynaud-Bouret, a mathematician at the Jean Alexandre Dieudonné Laboratory of Nice. The second, “Cognitive Sciences,” is headed by Emilie Gerbier and Damien Vistoli, both of whom are associate professors at Université Côte d’Azur. “These two courses, set up at the NeuroMod Institute, are designed to train tomorrow’s researchers, engineers and developers in interdisciplinary approaches to computational neuroscience and cognitive science,” explains Ingrid Bethus, who is also deputy director of the NeuroMod Institute. In addition to training students, these masters programs also provide a valuable pool from which Université Côte d’Azur research laboratories recruit the neuroscientists of tomorrow.

Olfactometer

TRANSMITTING INFORMATION WITH IONS

Like our sense of smell, our other senses depend on specific sensory receptors that are activated by perceived external stimuli and send this information via nerve signals to the brain. The brain then integrates all this information, decides what to do and sends instructions to our muscles so that we act accordingly. So there is a continual discussion between our brains and our bodies via electrical signals, that enables us to perceive and interact with our environment. However, these electrical signals are not based on the flow of electrons in wires, like the current that powers our electrical appliances, but on the movement of ions in neurons. The movement of these ions is ensured by dedicated cellular structures known as ion channels. “These protein structures are pores in the cell membrane that allow ions such as potassium, sodium, calcium or chlorine to pass into or out of the cell. In neurons, the passage of sodium and potassium ions across the membrane modulates their electrical potential and generates action potentials, the electrical signals essential

for the transmission of nerve impulses,” explains Florian Lesage, biologist and director of the Institute of Molecular and Cellular Pharmacology (IPMC) based in Sophia-Antipolis. Generally speaking, the structure of these ion channels makes them specific to one type of ion. However, Florian Lesage’s team has recently deciphered how a type of potassium channel called TWIK1 — which they discovered some thirty years ago — allows sodium ions to pass through under certain conditions. “Using numerical simulations, we were able to demonstrate that this pore reversibly changes structure when the pH drops to allow sodium to pass through instead of potassium,” adds the biologist. But, potassium channels inhibit neuronal activity, while sodium channels excite it. “Evolution has thus enabled the same channel to decrease or increase neuronal excitability depending on the pH of the medium.”

In addition to providing a better understanding of how ion channels work, this research could lead to

the development of new treatments. “Ion channel dysfunctions are associated with many neurological diseases and mental health disorders. Ion channels are therefore prime therapeutic targets,” the researcher states. In collaboration with a Japanese pharmaceutical company, his team is studying the role of a family of potassium channels called K2P — which includes TWIK1 channels — in chronic pain. “Such pain is often resistant to standard analgesics and is relieved by morphine. This opiate acts on receptors that change the activity of potassium channels. If we could target these channels directly with a drug, the pain should diminish without the side effects associated with morphine,” says Florian Lesage. Potassium channels are also involved in certain forms of migraine. Biophysicist Guillaume Sandoz and his team at the Valrose Institute of Biology (IBV) in Nice have revealed some of the genetic mechanisms responsible for this neurological disease that causes recurrent headaches. “Migraine attacks are caused by hyperexcitability in sensory neurons. In some migraine sufferers, specific mutations in the TRESK channel not only make it non-functional, but also impact TREK1 and TREK2 channels, which can no longer play their role in inhibiting electrical activity in these neurons, resulting in a migraine phenotype,” explains the researcher. Based on these results, his team discovered new pharmacological targets and identified agents for treating migraine. These researchers have also developed an optopharmacological tool that uses a simple beam of light to control pain and study its mechanisms. “We’ve created a molecule called LAK* that remotely activates TREK channels using UV light. In ambient light, this compound is inactive, but when exposed to UV light, it changes configuration and inhibits TREK channels, inducing acute pain. A UV beam therefore enables us to control with great spatial precision and in a reversible way the excitability of the neurons involved in pain in awake mobile animals,” explains Guillaume Sandoz. This tool is used to test new molecules with analgesic properties in animal models.

* Light Activated K+ Channel Inhibitor

ION CHANNELS, A STRATEGIC FOCUS OF IDEX

The study of ion channels in France has been historically associated with Université Côte d’Azur since the pioneering work of Michel Lazdunski. Lazdunski, the founder of the Institute of Molecular and Cellular Pharmacology (IPMC) in 1989 and CNRS Gold Medal winner in 2000, identified several new types of channels in the course of his career. He also explained the mechanisms governing them and contributed to their therapeutic applications. It was therefore only natural for IdEx to consider the study of ion channels as a strategic focus with a strong translational scope. “Many drugs target ion channels,” confirms Florian Lesage, current director of the IPMC. “For example, anti-epileptic drugs, certain painkillers, antiarrhythmics that regulate the heartbeat, anxiolytics to reduce anxiety and anesthetics.” But these drugs target only a tiny fraction of all ion channels. “There are hundreds of human genes that encode ion channels. Therefore, there are still many avenues of research to be explored, all of which represent potentially useful therapeutic targets,” enthuses the researcher who also coordinates the “Ion channels of therapeutic interest” Laboratory of Excellence (LabEx ICST). This national consortium of sixteen teams is also dedicated to studying channels with the aim of identifying new therapeutic targets.

In addition to potassium channels, sodium channels are also associated with neurological and psychiatric diseases. “Mutations in these channels, which are responsible for neuronal excitability, lead to a wide variety of pathologies such as epilepsy, schizophrenia, migraines and autism spectrum disorders,” explains Massimo Mantegazza, physiologist at the IPMC. For example, certain mutations in the SCN1A gene

cause developmental and epileptic encephalopathy (DEE) in young children. “Because of the interaction between the genetic mutation and repeated, longlasting epileptic seizures, these children have cognitive, behavioral and motor disorders and a high risk of mortality. These pathologies, which seriously affect the development of these children, are rare but have few therapeutic options,” adds the Italian researcher. Using various pre-clinical models, Massimo Mantegazza’s team is trying to identify, for each disease, the specific pathological mechanisms at work at different levels — nerve cells, neural networks, the brain and the organism as a whole — in order to propose possible treatments as part of a precision medicine approach. “First of all, we try to determine whether the mutations in question are associated with a loss of function, that is, the channels are dysfunctional and no longer work as they should, or with a gain of function, which means they are overactivated,” explains Massimo Mantegazza. For example, in some very severe developmental epileptic encephalopathies (known as NDEEMA and EIDEE) that affect newborns, the identified SCN1A mutation causes a gain of function in Nav1.1 sodium channels. This discovery has led researchers to propose an anti-seizure drug that inhibits the action of these channels. This

treatment has already been offered to dozens of children around the world, reducing the frequency of seizures in most of them. Massimo Mantegazza’s team is also interested in another DEE, Dravet syndrome, which is associated with a loss of sodium channel function. “In this case, treatments that block the channels could worsen symptoms and should be avoided,”says the researcher. In the absence of an effective treatment, the researchers have developed an algorithm that can predict almost 75% of epileptic seizures in these patients. “Based on the analysis of electroencephalogram data, which quantifies neuronal activity, this mathematical model helps family and caregivers prepare for a seizure,” adds the researcher. When therapeutic targets are identified, this model could also play a useful role in the decision to administer drugs before a seizure occurs, with the aim of reducing its severity or even preventing it altogether. Encouraging therapeutic strategies for this syndrome are currently undergoing preclinical evaluation as a result of the European SCN1A-UP! project, coordinated by Massimo Mantegazza. His team is also working to better understand the causes of premature mortality associated with Dravet syndrome, as well as with epilepsy in general, through the European projects Autonomic and Neurosense.

MEMORY PLASTICITY

Our nervous system does more than relay electrical signals. It is capable of recording information, storing it and retrieving it when it is needed. Despite decades of research, some of the neural mechanisms underlying this memory function remain elusive. “Memory is a complex cognitive process based on the connectivity of neural networks,” explains Hélène Marie, neurophysiologist at the IPMC. “Synapses, which propagate information between neurons, play a key role.” It is at this level that information is encoded by our nervous system. “Depending on its relevance, synapses are strengthened or weakened.” This phenomenon of synaptic plasticity allows our brain to retain information if it is important, or to forget it. One of the key mediators of this plasticity process is

the NMDA (N-methyl-D-aspartate) receptor. This assembly of proteins, which crosses the membrane of neurons at synapses, is the link between nerve cell excitability and the propagation of information. “When activated, these receptors function like ion channels, letting in ions such as calcium, which trigger the chain of cellular processes required by the cell to ensure transmission of the nerve signal to the next neuron,” explains the biologist. This receptor has another function, however, which is to reduce synapse activity. But the mechanisms underlying this atypical activity have long eluded scientists. As part of a long-term international collaboration, Hélène Marie’s team has revealed this process, which helps regulate synaptic activity and thus connectivity between neurons.

LETTING THE BODIES OF NON-VERBAL AUTISTIC CHILDREN SPEAK

Autism spectrum disorders are a group of neurological conditions that affect behavior, sensoriality and social interaction. In the most severe cases, children do not acquire language. “Children with these severe disorders therefore have difficulty expressing their stress, anxiety or even simply pain,” says Susanne Thümmler, a child psychiatrist at Nice’s CHU Lenval and a researcher specializing in neurodevelopmental disorders at Nice’s CoBTeK laboratory. Some therefore express their discomfort linked to sensory or emotional overload through behavioral disturbances, agitation, anxiety, or even aggression towards themselves or others. Unfortunately, “the drugs available to us to calm these crises are often of limited effectiveness, and have undesirable side effects. Nondrug treatments are sometimes more effective when introduced before the crisis,” continues the researcher. But how can you tell when a

behavioral crisis is about to erupt in children who have not yet acquired language? This is where the AI-Wear project, in which Susanne Thümmler is involved, comes in. “This project, coordinated by Esma Ismailova of the Provence Microelectronics Center and involving several academic and private-sector partners, seeks to identify stress indicators in non-verbal autistic children, such as increased heart rate, higher respiratory rate and excessive sweating. The idea is to develop a virtually invisible, wire-free skin-contact device, like a temporary tattoo, that would detect these physiological signs of stress before a crisis is triggered.” The family and/or caregivers could then intervene to better support, or even prevent, extreme reactions and behavioral crises. “This tool could simplify the care of these children while reducing the need for medication, with a consequent improvement in quality of life for the children and their families.”

It all began in 2015, when these scientists identified a new molecule produced in the brain that inhibits the activity of neurons in the hippocampus, a brain structure essential in the processes of memorization and spatial localization. “This molecule, called AETA, is a peptide derived by cleavage of the APP protein, which is known to be involved in Alzheimer’s disease,” continues the researcher. The amyloid beta peptide is also produced from this protein, and aggregates into plaques in the brain of patients suffering from this neurodegenerative pathology. Since then, these researchers have been trying to uncover the mechanisms through which

the AETA peptide reduces neuronal activity. Using electrophysiology techniques, functional imaging, molecular tools and mouse models, they have shown that this peptide causes a change in the shape of the NMDA receptor, which then adopts the atypical function of reducing neuronal activation by weakening synapses. This loss of synaptic activity is central to the pathophysiology of Alzheimer’s disease, particularly in the early stages before neurons die. Preliminary data from Hélène Marie’s team suggest that AETA levels are increased in the brain of Alzheimer’s patients. This peptide could therefore represent a new therapeutic target in the

treatment of this and other diseases. “In addition to Alzheimer’s disease, NMDA receptor dysfunctions have been observed in other neurodegenerative diseases such as Parkinson’s and Huntington’s, as well as in autism, epilepsy, schizophrenia and depression,” explains the biologist. Her team, with the support of CNRS Innovation, is working to exploit this research and develop innovative treatments, particularly for Alzheimer’s disease, for which there are currently no effective treatments.

In addition to the regulation of synapses by NMDA receptors, many other cellular mechanisms are required for memory formation. The team led by iBV biologist Florence Besse focuses on the spatial regulation of gene expression in neurons via

messenger RNA, or mRNA, the molecular chains that carry genetic information out of the nucleus to produce biologically active proteins. “The transport of messenger RNA is important for the local production of proteins that mark the synapses activated during the transmission of information,” explains the biologist. These “markers” allow our nervous system to remember this information. But, “neurons are special cells with cell extensions that can be very long. Some of the axons through which action potentials propagate are over a meter long,” continues the researcher.

To better understand this regulation of gene expression at synapses, Florence Besse and her colleagues are using a simple animal model, the

Drosophila or fruit fly. “Its brain displays the same logic of neural circuit construction as humans, but with only 140,000 neurons, whereas our brains have several tens of billions of interconnected nerve cells,” explains Florence Besse. Scientists use this experimental model when viewing a working brain through high-resolution microscopes and observing the connections established on the scale of nerve cells and neuronal circuits. By disrupting RNA transport, they have shown that the integration of stimuli at the synapse level depends on local mRNA populations. “The control of gene expression in neurons is therefore decentralized,” adds the biologist. “Cell body-independent regulation of protein production is in fact necessary for rapid response to stimuli and neuronal activity.” These researchers have also shown how mRNA produced in the nucleus can be recruited into complex molecular assemblies, called neuronal granules, before being transported to the synapses in a controlled distribution. And “if the transport of these mRNA-containing granules is disrupted, the formation of the memory is lost.” This local regulation of gene expression is important for information communication and storage, as well as for brain maturation. “These processes contribute to neuronal plasticity, the extraordinary ability of neurons to adapt and remodel themselves according to context.”

Florence Besse and her team are now working to understand the impact of aging on these mechanisms, in particular on the properties of the granules, while also looking at neurodegenerative diseases such as Charcot’s disease, in which these granules form aggregates.

From fundamental biology to clinical applications, Université Côte d’Azur is heavily involved in neuroscience research, helping to advance this promising field on a global scale, not only to better understand how our nervous system functions, but also to offer new treatments and care when it malfunctions.

Simon PIERREFIXE Science journalist

PROFILE Jérôme D ELOTTE Christia n PRADIER

Interview with Jérôme DELOTTE and Christian PRADIER about the Educational Leadership Chair in women’s health (CLE), led by Université Laval and Université Côte d’Azur

How did the idea come about of creating an educational chair in women’s health shared by Université Laval and Université Côte d’Azur?

The idea first arose during an initial university visit to Quebec. The meetings that took place during the visit provided an opportunity to discuss specific themes, in particular women’s health. Following these meetings, a number of discussions between the two universities led to the idea that there was scope for developing the theme of women’s health, and so the project to create an Educational Leadership Chair (CLE) in women’s health was born.

What do you mean by the term “leadership” in the title CLE?

It’s a Quebec term. But when we talk about “leadership,” we’re talking about setting the standard for teaching and research in a given field, through the development of innovative, high-quality programs.

How long has Université Côte d’Azur been working specifically on women’s health?

Women’s health has long been a focus of our research, due to the activities of the Nice University Hospital (CHU), which is part of Université Côte d’Azur. In the obstetrics and gynecology department and in public health, we’ve been taking care of women’s health for many, many years. So the CLE has been a driving force in encouraging dialogue on a key theme of the University’s research, in particular in the medical disciplines.

In general, is women’s health still underresearched today?

Studies on women’s health are gaining in importance, precisely because there remains a deficit. We therefore need to improve our knowledge in this particular field, with all that this implies, for example the care of specific pathologies or the management of violence against women.

It’s an absolutely immense field; there’s not a single area where issues of inequality don’t arise. It’s a universal phenomenon. There’s still a lot to do.

What educational and research projects have been set up under this CLE so far? And what projects have you been able to establish thanks to the CLE that you

would certainly not have been able to put in place (or not as quickly or efficiently) without it?

First, we organized an international symposium on women’s health, with a congress in Quebec and one in Nice.

In terms of teaching, simulation workshops in urogynecology were set up, with discussions between experts from Nice and Quebec. These simulation workshops were used to establish programs for residents and seniors.

A MOOC will be launched in April 2025 on a teaching platform open to the general public but also to students and healthcare professionals, with content written by experts from the two universities.

We have also created a training module on genital mutilation, because in France we have a certain expertise on the subject. It’s a theme that has been of great interest to our Quebec colleagues. An online module has been set up on this topic.

In addition to pedagogical discussions between students from the two universities, two professors from Université Laval have been appointed to Université Côte d’Azur. Our Canadian colleagues were able to supervise the work of midwifery students, as well as final dissertations. Posters created as part of this collaboration have also been awarded prizes.

We’re also developing fellowships in Canada for French students, with priority given to Université Côte d’Azur students through the CLE.

Lastly, there are some less formal actions linked to the discussions we’ve had with our Quebec colleagues, notably on the subject of violence against women. For example, on November 25, 2024, we inaugurated the Maison des Femmes, a treatment center for women victims of violence, at the Nice University Hospital (CHU). Our discussions have ultimately helped us to initiate a range of clinical, educational and research projects on this topic.

More generally, and in addition to these projects, there’s a very positive momentum, as this partnership is blazing a trail and encouraging other related projects. It’s very promising. This collaboration has clearly given rise to a number of educational projects that would not otherwise have been possible.

You mentioned differences in the way the two countries operate. In terms of content, was it interesting to work with another country and did you identify any differences in terms of management or operations, and did this have an impact?

Absolutely. That’s part of the appeal of working with people who live somewhere else. We can have societal discussions about the provision of care in different countries, but also about the organization of care in these two very different regions. As an example, in Quebec, urogynecology is a discipline in its own right, whereas in France there are two distinct specialties: urology and gynecology.

To conclude, is there any particular topic you’d like to highlight?

It’s hard to single out any one particular topic because, ultimately, what was most interesting was the fact that this partnership created a bridge across all the themes we wanted to develop. I’d like to applaud the mutual influence we’ve had on a daily basis over the years.

To take it a step further, there really is a synergy effect. In the end, we’ve achieved more than we set out to do, and the prospects are extremely exciting. On women’s health in particular, we’re thinking of developing a shared database between Université Laval and Université Côte d’Azur, which could give rise to comparative studies. Based on the MOOC, we also want to give a boost to university degree and master’s courses, particularly in the public health approach to gynecology, which would address both medical and societal aspects.

Spotlight on the Academies of Excellence Spotlight of Excellence

Thanks to the momentum provided by IdEx, the Academies of Excellence are spurring creativity and rejuvenating research at Université Côte d’Azur.

This section highlights new concepts and innovative research projects arising from the inter- and transdisciplinary interactions within the Academies of Excellence.

AN AI SYSTEM TO SPEED UP MOLECULAR RESEARCH ON LIVING ORGANISMS

Faced with the explosion of biological data, researchers at Université Côte d’Azur are developing a revolutionary AI that is simplifying their analyses and paving the way for major discoveries in the life sciences.

The revolution in omics,* driven by techniques such as metabolomics, has generated an unprecedented flow of essential data on biological systems. Their interpretation, however, remains a major challenge because it requires skills in chemistry, biology and computer science, and often many years of collaborative work.

Faced with this challenge, researchers at Université Côte d’Azur coordinated by Louis-Félix Nothias (Nice Institute of Chemistry) and Fabien Gandon (Inria) are exploring the potential of generative artificial intelligence combined with a metabolomic knowledge graph for simplifying and accelerating the analysis of these complex data. The potential

applications are endless and are likely to accelerate discoveries in fields such as marine biology, clinical research and environmental ecology.

The KG-Bot project, supported by Academy 1 (funding a one-year postdoctoral grant) and by 3IA Côte d’Azur, aims to leverage access to chemical data obtained by mass spectrometry. The system identifies and contextualizes metabolites using AI that links experimental data to scientific literature via a knowledge graph. The researchers use a natural language interface to interact with complex data by asking specific questions. A researcher can ask which sample contains the highest proportion of a given molecule, for example, and receive a direct and clear answer that can be viewed as a graph.

Development of the first version of KG-Bot laid the foundations for MetaboLinkAI, an international research project co-funded by the Swiss National Science Foundation (SNSF) and the French

National Research Agency (ANR) scheduled to start in 2025. With a budget of 4.9 million euros and partners that include CNRS and the Swiss Federal Institute of Technology (ETH Zurich), the project is setting out to create an encyclopedic platform of metabolomic data that can be queried using advanced AI algorithms. By merging biomedical and fundamental knowledge, MetaboLinkAI hopes to improve the efficiency of scientific research and broaden the scope of testable hypotheses and thus pave the way for new discoveries in the life sciences.

Researchers also plan to integrate other types of omics analyses to develop a complete system that can operate at different molecular levels and provide a comprehensive view of biological systems. This initiative could transform the way the scientific community addresses complex questions in molecular biology and lead to further discoveries in fields as diverse as marine biology, clinical research and environmental ecology.

Definition

Omics techniques are the methods used to study all the elements of a biological system collectively and simultaneously (such as genes with genomics, proteins with proteomics or molecules with metabolomics) to gain a deeper understanding of their dynamics.

Dr Louis-Félix NOTHIAS, CNRS researcher, Holder of the Metabolome and Holobiont Junior Professor Chair Nice Institute of Chemistry and Interdisciplinary Institute for Artificial Intelligence (3IA) Côte d’Azur

Dr Fabien GANDON, Inria Senior Researcher, I3S Inria and Interdisciplinary Institute for Artificial Intelligence (3iA) Côte d’Azur.

EDUCATION RESEARCH INNOVATION

EXCEPTIONAL VENUES

Georges Méliès Campus - Component Institution of Université Côte d’Azur

THE GREEN BOOK SPOLIGHT ON TRANSDISCIPLINARY APPROACHES

Transdisciplinary approaches in research projects on the sustainability of our societies, environments and ecosystems.

Since the 16th century, our fundamental knowledge of our place in the universe has undergone tremendous changes. The same is true for our relationship with our environment or with what we call “nature.” These changes have been brought by advances in anthropology, sociology and the natural sciences. Our understanding of “nature” has equally changed radically over the last few centuries. And even if we knew that “Galileo’s earth could rotate, [...] it had no tipping point, no planetary boundaries, no critical zones. It was capable of movement, but not of behavior. In other words, it was not yet the Earth of the Anthropocene”1 (term formalized by P. Crutzen and E. Stoermer in the late 90s2).

This paradigm shift calls for new approaches, and it is in this context that the IdEx Academy of Excellence Environment, Risks and Resilience is supporting research projects focusing on the study of the

sustainability of our societies, our environments and, more generally, our ecosystems. It is attempting to explore as fully as possible the concepts relating to the possible transition from the Holocene to the Anthropocene, which covers the study of (terrestrial) space, human cultural achievements, political and economic systems and a variety of environmental impacts.3 The research projects brought together and supported by the Academy are therefore necessarily transdisciplinary, as they address challenging questions about objects or systems that are obviously complex in nature and diversity. Thus, “[...] as its prefix ‘trans’ indicates, transdisciplinarity is the scientific, epistemological and intellectual stance that is found at once between, across and beyond disciplines and compartmentalized approaches.4

To illustrate its many actions and provide an overview of projects and prospects in this field, the Academy of Environment, Risks and Resilience publishes a “Green Book” every five years.5 The second edition, now available, covers the period from 2020 to 2024. It is organized around the

copyright Christophe Den Auwer

©

four defining themes of the Academy, which also correspond to SDG clusters:6 Anthropogenic health and environmental risks; natural hazards and their impact on the environment, cities and society; energy- and resource-related environmental challenges; and threats to oceans and coastal areas.

We hope that this edition will be the inspiration for new research ideas and new collaborations, and especially, that it will give us the scientific audacity to face the challenges that are driving research in this Anthropocene era.

1 B. Latour, Face à Gaïa Ed; La Découverte, France, 2015.

2 P. J. Crutzen, Nature 415:23, 2002 or Crutzen, P. J. & Stoermer E. F., Global Change Newsletter, 41, p. 17-18, 2000.

3 S. L. Lewis, M. A. Maslin, Nature, 519:171, 2015

4 L. Dupuy, “Co, multi, inter, ou trans-disciplinarité ? La confusion des genres…” , CIEH (Certificat International d’Écologie Humaine), 2004 (1st version), 2021, retrieved September 2024 from http://web. univ-pau.fr/RECHERCHE/CIEH/documents/La%20confusion%20 des%20genres.pdf.

5 M.-Y. Bottein, C. Den Auwer, D. Fox, A. Galve, F. Grognard, M. Le Gourrierec, J.-C. Martin, L. Porcherie (eds), The Green Book of the Academy Space, Environment, Risk and Resilience, September 2024.

6 Retrieved April 2024 from https://sdgs.un.org/fr/goals.

EDUCATION RESEARCH INNOVATION

EXCEPTIONAL VENUES

SophiaTech Campus - Component Institution of Université Côte d’Azur

ODIN,

THE NEW OMICS DATA INTEGRATION NETWORK CREATED BY THE BIOINFORMATICS COMMUNITY OF UNIVERSITÉ CÔTE D’AZUR

With the constant increase in the volume of biological research data, storage, access to and processing of multi-omics data has become essential for the success of large-scale scientific projects. The research teams and technical platforms of Université Côte d’Azur’s biology laboratories often lack the bioinformatics resources needed to analyze and process genomic, proteomic, cytometric and imaging data. These different types of data are mostly analyzed independently, platform by platform, project by project or team by team.

The ODIN project is building a network of bioinformaticians to support the research conducted by Université Côte d’Azur teams. The initiative includes creation of a web portal to manage statistical analyses, led by Dr Marin Truchi, a research engineer specifically hired for the task by the Academy of Excellence 4 Complexity

and Diversity of Life. Marin Truchi is developing this network under the supervision of Dr Kévin Lebrigand, who was in charge of bioinformatics for the UCA_GenomiX functional genomics platform for 19 years (from 2003 to 2022), and who was the founder of the CoBiODA Bio-Informatics network in 2023 at the IPMC (CNRS, VALBONNE).

The ODIN network will be used to monitor analyses throughout the life of scientific projects. The network should create an emulation around bioinformatics resources, step up pooling efforts and contribute to the cross-disciplinary integration of heterogeneous data sets produced by the different technical platforms of the university. Research teams will be able to find the high-performance bioinformatics support they need to produce high-impact publications and contribute to greater visibility of the research activities of biology laboratories.

Omics Data Integration Network (ODIN), an interdisciplinary and multi-omics (genomics, proteomics, cytometry, imaging) project of Université Côte d’Azur that brings together multiple institutes (IPMC, IRCAN, IBV, ISA) to: (1) Document and organize data analysis resources and expertise; (2) Implement a data management system for research projects; (3) Standardize, share and disseminate data analysis guidelines; and (4) Optimize the scientific output of research teams within the Côte d’Azur community.

To achieve this goal, a bioinformatics analysis management web portal will be set up, that provides a system for monitoring and archiving analysis scripts. Based on Laboratory Information Management Systems (LIMS) such as UCA_ GenomiX, Mediante and MICA / Omero, the web portal will enable longitudinal follow-up of research project analyses and their documentation and provide long-term storage for scripts and analysis objects from project kick-off through to final publication. The portal provides the means to share and reuse analysis scripts, find assistance in bioinformatics, browse documented publications by partner research teams and select, according to research project and input data, the analyses and graphs needed to explore their omics datasets. Researchers will be able to produce the images they need for their publications more quickly. The approach will be based on the FAIR (Findable, Accessible, Interoperable, Reusable) principles of omics data analysis, which are fundamental for research reproducibility.

A first version of the portal: https://www.genomique.info:8443 /odin/index is being developed on the IPMC bioinformatics platform, in partnership with the IRCAN platform (Olivier Croce, IgR CNRS). This new resource will improve the dissemination of analysis tools, methods and best practices within Université Côte d’Azur.

Marin TRUCHI

PhD in Life Sciences from Université Côte d’Azur, Université Côte d’Azur Research Engineer at the IPMC on the ODIN project, supported by IdEx Academy 4 Complexity and Diversity of Living Systems.

Dr Kévin LEBRIGAND, Postgraduate degree in bioinformatics

Université PARIS VI, PhD in life sciences from Université Côte d’Azur, CNRS Research Engineer at IPMC, Founder of the CoBiODA bioinformatics network at IPMC, Director of the ODIN platform at Université Côte d’Azur.

INTERSECTING ECOCRITICISM WITH RACE STUDIES:

HOW FUNDAMENTAL RESEARCH CAN SHED LIGHT ON ACTIONS WITH A SOCIAL IMPACT

Ecocriticism is a field of research in literature and, more generally, in the humanities and social sciences that focuses on environmental issues. Since it emerged in the 1990s, it has developed approaches that have become increasingly interdisciplinary. The shared objective is to analyze different types of texts and discourses (literature, film, environmentalist rhetoric, etc.) and examine how authors, as members of a social class or society at a given time, represent the environment and the relationship of humans and societies with nature. The study of these representations includes the identification of biases and preconceived ideas to explain their causes and how they are constructed.

Ecocriticism also provides a historical context for the relationship between humans and nature and the

practices that stem from it, and how this relationship changes or remains static throughout different periods, thereby shedding light on the representations that are more rooted in the organization of humannature relationships and those that are influenced by the dominant ideological ideas imposed during different periods. In environmentalist rhetoric, for example, the concern has moved from the causes of human-induced climate change to an emphasis on action and solutions to the problem.1

The process of decentering and historicizing the relationship between humans and nature also involves analyzing the power relationships that run through societies, produce social norms and define dominant interpretations of what is a good solution. Ecocriticism therefore shows that the presuppositions

for these interpretations are not static, but are socially constructed, and provides the keys to identify what can change and how.

Emmanuelle Peraldo and Nora Galland are studying these issues at CTELA in collaboration with LIRCES and GREDEG colleagues. Their research project on “Ecocriticism and Race Theories in the Humanities from the 16th to the 18th Century” intersects ecocritical approaches with critical studies of “race” and shows that in the literature of the 16th, 17th and 18th centuries the concept of “race,” understood as a social construct, was shaped by the way relations between human beings and nature were expressed. The racial imaginary was projected on nature, which was used to express the power relationships between human beings through images of flora, fauna and climate. The project delves into power relations and analyzes how the representation of “nature” was used to legitimize the

colonization and domination of those perceived as being “closer” to nature.

This interesting project opens up perspectives in multiple fields, notably by applying the analysis of interactions between nature and society to the study of actions with a social impact.

Emmanuelle PERALDO

Professor of English and AngloSaxon literature, Director of CTELA

Nora GALLAND PhD in English Language and Literature

1 Kjersti Fløttum, “Le changement climatique en discours”, Cahiers de praxématique [online], 73 | 2019, published online May 6, 2020, retrieved September 17, 2024. URL: http://journals.openedition.org/praxematique/5746; DOI: https://doi.org/10.4000/praxematique.5746

CTELA, Transdisciplinary Center for the Epistemology of Literature and the Performing Arts, investigates the specificity of literary and artistic phenomena and how they evolve. This laboratory focuses on transdisciplinarity (relations between literature and other forms of cultural expression).

FROM MECHANOBIOLOGY TO THE MECABIONIC PROJECT

HOW OUR CELLS AND TISSUES RESPOND TO THEIR MECHANICAL ENVIRONMENT

One of the aims of the grant for thematic semesters offered by the Academy Complex Systems is to provide an opportunity to shed light on new, underresearched, scientific themes. Mechanobiology belongs to that category. It a fast-growing field that studies the response of cells and tissues to their mechanical environment during various biological processes, such as carcinogenesis or embryogenesis.

The MecaBioNic project, led by Rachele Allena, professor and researcher at the JeanAlexandre Dieudonné laboratory, grew out of a mechanobiology working group set up at Université Côte d’Azur by collaborating laboratories (LJAD, IRCAN, IPMC, IBV, C3M, Inria).

This project builds on recent major advances in mechanobiology that make it possible to observe in vitro how cells behave, and more specifically how their shape changes under specific types of stress (i.e., traction or pressure), and how they reorganize their cytoskeleton or trigger molecular and/or chemical responses. A major challenge in this field is to understand mechanotransduction, i.e., the molecular mechanisms by which cells detect and respond to mechanical signals. While medical research has usually sought to find the

genetic and biochemical origins of diseases, advances in mechanobiology suggest that changes in cell mechanics, in extracellular matrix structure or in mechanotransduction may contribute to the development of many diseases, including atherosclerosis, fibrosis, asthma, osteoporosis, heart failure and cancer.

This field necessarily requires interdisciplinary approaches combining biology with physics, optics, and mechanical and mathematical modeling.

This thematic semester is an exceptional opportunity to convene scientists with complementary training, skills and knowledge and develop an international scientific community through a series of seminars, colloquia and summer schools. It gives Université Côte d’Azur a stronger role in studying this innovative aspect of mechanics and could lead to a new institute of mecanobiology in Nice in the years to come.

Information and events: https://univ-cotedazur.eu/events/mecabionic

Rachele ALLENA Professor and researcher Jean-Alexandre Dieudonné Laboratory

OUTside the BOX

The Innovation Program of the Université Côte d’Azur Initiative of Excellence aims to support the development of innovation and to finance public-private partnerships. In this section, learn more about projects that are helping to commercialize major or radical innovations based on Côte d’Azur research, supported by IdEx.

Eyenav Robotics

Eyenav Robotics was founded in December 2023 and is enjoying great success, most recently with a major commercial partnership with one of France’s leaders in the marine and underwater robotics industry. The company supplies advanced servo modules, specially designed for the perception, localization and autonomous navigation of underwater robotic vehicles, to civil and military drone manufacturers. These modules incorporate cutting-edge technologies such as next-generation sonar and smart underwater cameras, combined with advanced algorithms and artificial intelligence. At the same time, Eyenav Robotics provides engineering services and expertise in underwater robotics, addressing the complex challenges of the deep sea.

High-speed wireless communication and GPS cannot be used on a fully submerged robot due to the attenuation of electromagnetic waves in water. Traditionally, inertial sensors are used, but these suffer from significant drift over time, considerably complicating robot localization and making autonomous navigation particularly complex. One of the solutions commonly used to compensate for the absence of GPS is the SLAM (Simultaneous Localization and Mapping) technique, which enables localization relative to the environment.

However, without high-performance detection modules, vision-based SLAM comes up against the unique challenges of the underwater environment, where visibility is often reduced to a few meters due to water turbidity, floating sediments and poor lighting conditions.

The technologies developed by Eyenav Robotics stand out for their innovative nature, the fruit of over ten years’ research by Université Côte d’Azur and CNRS. Founded by Minh Duc Hua, Tarek Hamel and Lam Hung Nguyen, Eyenav Robotics exploits these advances to push back the frontiers of underwater navigation. Its innovations significantly enhance the capabilities of underwater drones in terms of perception, localization and navigation.

The smart cameras marketed by the startup incorporate HomographyLab software, which offers three key functions: dynamic stabilization, localization and autonomous inspection of pipelines or undersea communication cables. This software was developed by the OSCAR team at the I3S laboratory in Sophia Antipolis. The Université Côte d’Azur IdEx supported its development as part of its “Deeptech Startup” call for projects.

In the future, Eyenav Robotics plans to enhance its technologies to improve the capabilities of underwater drones for inspection and deep-sea exploration. This will include the development of a new generation of smart forward-looking sonar (FLS) devices, designed to offer optimized longrange detection of distant objects, even in extreme aquatic conditions.

Eyenav Robotics also aims to offer custom-made underwater robots, for both civil and military purposes, in particular for offshore site inspection and surveillance.

LAM HUNG NGUYEN TAREK HAMEL MINH DUC HUA

Virtu Therapeutics

A team of researchers from Université Côte d’Azur led by Thierry Virolle, Senior Researcher at Inserm,1 has devised an innovative therapeutic strategy to target Cancer Stem Cells (CSCs) in tumors by inducing them to differentiate. This “therapeutic differentiation strategy” is being commercialized by a young startup, Virtu Therapeutics, founded in December 2023.

Its founders Thierry Virolle, Laurent Turchi, Patrice Cornillon, Fabien Almairac and Lionel Menou, all from medical, academic or industrial backgrounds, are focusing on developing a treatment for glioblastoma, a cancer that is currently incurable in adults and children and which illustrates the CSC model of cancer development.

The differentiation treatment forces the glioblastoma cancer stem cells to evolve towards an indolent and differentiated tumor phenotype, with no ability to initiate or advance a tumor, thus limiting tumor growth or recurrence. The differentiated tumor cells resulting from this therapy are also more sensitive to conventional chemotherapies. Therefore the treatment could considerably improve the survival rates of patients suffering from this disease. Furthermore, Virtu Therapeutics is opening the way for new cancer therapies based on the same model.

This approach involves the use of a flagship molecule developed and patented at the Valrose Institute of Biology,2 in collaboration with the Université Côte d’Azur Nice Institute of Chemistry3 and the Nice University Hospital.4 The safety and in vivo efficacy of this molecule, named DV188, particularly in combination with standard chemotherapy, have been demonstrated.

The technology developed by Virtu Therapeutics has benefited from “Deeptech StartUp” funding from the Université Côte d’Azur IdEx Innovation Program, complementing support from the technology transfer accelerator, SATT SUD EST, and the cancer research hub, Cancéropôle PACA. In 2023, the company also won the prestigious i-Lab competition, sponsored by BPI. This funding enabled the company to embark on a new phase of development leading up to 2025.

Currently, the team plans to raise funds and build partnerships with major pharmaceutical companies working on oncology drugs. The support of investors and manufacturers will help secure and accelerate the various stages of the pre-clinical phase, and then the clinical trials of the drug candidate. It usually takes around ten years to develop a drug, but it could reach the market much more quickly in this case due to the great medical need to address this highly aggressive cancer, if the first results in humans are similar to those already observed in vivo

1 Inserm: https://www.inserm.fr/en/home/

2 Valrose Institute of Biology: http://ibv.unice.fr

3 Université Côte d’Azur Nice Institute of Chemistry: https://icn.univ-cotedazur.fr

4 Nice University Hospital: https://www.chu-nice.fr

Lionel MENOU Founder General Director

Fabien ALMAIRAC Board member

Thierry VIROLLE Founder Research Director Laurent TURCHI Founder Scientist and CTC

Patrice CORNILLON Founder Board member

INNOV&SEA

The preservation of coastlines and the ocean floor is a major challenge. Degradation of these environments affects planning and environmental policies, as well as the economic development of maritime areas. Moreover, “Ensuring the resilience of maritime and coastal regions and ecosystems” and “Supporting the competitiveness of our maritime and coastal blue economy” are two of the major priorities set by the French government for the next six years. They are set out in the 2030 French National Strategy for the Sea and the Coast (SNML).

Innov&Sea was financed by the Université Côte d’Azur IdEx Innovation Program through the “Deeptech Startup” call for projects. It aims to provide solutions to private and public stakeholders involved in the immense challenge of safeguarding marine biodiversity by offering a method for assessing the toxicity of products and pollutants discharged into the marine environment.

Dr Pauline COTINAT President Co-founder Emmanuel MICHELOT Head of Business Development Co-founder

BARNAY-VERDIER Scientific Expert Co-founder

Innov&Sea provides a technological resource for companies wishing to estimate the impact of their activities on marine ecosystems. The technique involves assessing in vitro the cytotoxicity of a substance on two cell cultures that are derived from the animal cells and microalgae (photosynthetic dinoflagellates) of the symbiotic sea anemone Anemonia viridis. In this way, manufacturers (particularly in the cosmetics sector) can measure the effects of the ingredients of their products on a biotic environment, and develop formulations that are more respectful of marine biodiversity.

Furthermore, this method makes it possible to: (i) obtain accurate and complete results in just two weeks, and (ii) assess a wide range of product toxicity levels, in an eco-responsible way. In fact, by assessing ecotoxicity using in vitro tests, that is, exclusively on cells in culture, the “3Rs” of humane research (Reduction, Replacement, Refinement) can be respected and the impact on marine biodiversity prevented, thus offering an alternative to methods that use live marine animals.

The technology developed by Innov&Sea is the result of eight years of laboratory research, supported by the CNRS, Université Côte d’Azur and Sorbonne University. To date, it is the only non-

Dr Stéphanie

Pr Paola FURLA Scientific Expert Co-founder

invasive method for testing ecotoxicity to marine organisms, and consequently the only one fully in line with United Nations Sustainable Development Goal 14 “Life Below Water.”

Innov&Sea was created in 2023 by Pauline Cotinat, Emmanuel Michelot, Stéphanie Barnay-Verdier and Paola Furla, and in its first year has obtained major contracts with several Côte d’Azur and national cosmetics companies. The company has also won several prizes and awards (finalist in the Cosmetic Victories 2023, winner of the Cergy-Pontoise region’s Cosmé-Tech 2023 Challenge, winner of the Entrepreneurship in Research award from the Nice

Côte d’Azur Metropole and more recently, winner of the Monaco Ocean Protection Challenge). Its acceleration phase will be boosted in 2025 by new national and international contracts in the cosmetics sector, and also by the expansion of its technology into new markets, such as marine biomonitoring (with “Bourse French Tech Emergence” funding from Bpi France). Thanks to the growth of its business and the launch of R&D activities, Innov&Sea plans to hire at least two new employees within the next year.

For further information: https://innovandsea.com contact@innovandsea.com

CHANGING

Alexandre Doctoral student in biology

Ornelle Law student

Virginia D’AURIA Quantum physics faculty member

Joint Europe Office

All-around support for a European research strategy

The first in the region Created in 2016 under the impulse of Université Côte d’Azur IdEx

- Flagship LEADEuRope program to encourage European grant winners and detect new talents

- ERC Booster program to support applications for ERC grants

- MSCA Booster initiative to support applications for postdoctoral grants

- Europe Office Hors les Murs to meet laboratories

- Info days and seminars for the scientific community

- Individual meetings to prepare for your European career

A single address: cellule-europe-mutualisee@univ-cotedazur.fr

Our members

Agenda IdEx semester 1, 2025

Wednesday, February 5, 2025

IdEx Young Researcher Awards at 1 p.m. at the Château de Valrose theater

Monday, March 17, 2025 Applications close for Excellence Fellowships for Young Researchers

Tuesday, March 18, 2025: Applications close for Advanced Research Program grants

June 17 to 20, 2025: International Workshop on UI GreenMetric at UniCA

IdEx, driver of excellence and development IdEx, driver of excellence and development

A closer look at the Initiative of Excellence of Université Côte d’Azur