A bioengineer, Louise Thines completed her dissertation in molecular and cellular biology at UCLouvain before continuing her research for three and a half years in Washington, D.C., in the United States. She then joined the University of Namur for a new postdoctoral fellowship in Professor Henri-François Renard’s laboratory, with support from MSCA funding.

In tissues, cells are constantly interacting with their neighbors and their environment. Certain proteins present in the cell membrane play a direct role in these interactions. This is the case with cell adhesion molecules, often referred to by the acronym CAMs.

These CAMs can be compared to tiny molecular Velcro fasteners that help keep cells in contact. They also play a role in transmitting signals into the cell and can influence the cell’s organization, movement, or interactions with neighboring cells. To control these interactions, the cell can add certain proteins to its membrane, move them, recycle them, or remove them. One of the mechanisms used to bring them into the cell is endocytosis.

CAMs play an important role in the ability of tissues to form, renew themselves, and repair themselves. During embryonic development or wound healing, for example, certain cells must modify their contacts with neighboring cells in order to change position and participate in tissue remodeling. By adjusting the adhesion molecules on their surfaces, they can strengthen certain contacts, loosen others, and become more mobile. This ability to modify intercellular adhesions is essential for the body’s normal functioning.

During the process of endocytosis, the cell membrane bulges around a molecule on its surface. It gradually forms a pit that eventually closes off inside the cell, taking the form of a small vesicle. 

Endocytosis can occur through several “pathways.” It’s a bit like a building with several types of doors operated by mechanisms that use different technologies. 

The best-characterized pathway today involves a protein called clathrin, which, thanks to its structure, causes the cell membrane to curve inward until a vesicle is formed. But not all molecules follow this route.In 2020, research by Henri-François Renard revealed another endocytosis pathway. This pathway operates independently of clathrin and involves, in particular, endophilin-A3 to facilitate the entry of adhesion molecules into the cell.

It is this mechanism—which is still not fully understood—that lies at the heart of Louise’s project.

Why is this so important? Because in certain cancers, tumor cells can lose their ability to adhere, gain greater migratory capacity, and invade neighboring tissues. This process contributes to the various stages that can lead to the formation of metastases. Understanding how CAMs are removed or maintained on the cell surface therefore also provides insight into certain mechanisms associated with tumor progression. Furthermore, certain viruses can use CAMs as “Velcro” by attaching to them to gain entry into our cells. Targeting the CAM entry point could therefore be a promising strategy for combating certain viral diseases.

Louise is trying to determine how this endocytosis pathway works at the molecular level. Which molecules are involved? How do they interact? What triggers the internalization of an adhesion molecule into the cell? What happens when one of the components involved in this mechanism is disrupted?

In particular, Louise is studying the “Velcro” protein CD166, a cell adhesion molecule (CAM) found on the surface of various cells.

To understand what is happening, Louise is working with human cancer cells grown in the laboratory.

She can modify the activity or abundance of proteins suspected of being involved in the mechanism, using genetic tools or chemical compounds. She then observes the consequences of these disruptions.

Microscopy plays a central role here. Using fluorescent markers, it becomes possible to visualize different proteins within the cells and track their location. Louise can thus simultaneously observe endophilin-A3 and the adhesion molecules that have been internalized into the cell’s cytoplasm.

The images serve not only to illustrate the experiment. They become data that the researcher can quantify and compare to determine whether an experimental modification accelerates, slows down, or disrupts endocytosis.

To better understand the mechanisms of this endocytosis pathway, Louise is also seeking to identify other proteins that may be involved in its function.

In collaboration with the University of Geneva, she is testing hundreds of chemical compounds capable of affecting various proteins within the cell. After each treatment, images are automatically captured under a microscope to observe whether the endocytosis process is altered. Most of the compounds tested will likely have no particular effect. But if one of them significantly slows down or disrupts the mechanism, it is the protein it targets that becomes particularly interesting: it could be involved, directly or indirectly, in this endocytosis pathway. Further analyses are then needed to verify its role. These compounds are thus valuable tools for research. By blocking a protein and observing the consequences on the cell, researchers can gradually understand its function.

Certain molecules capable of modulating this pathway could also, in the longer term, open up avenues for new therapeutic strategies. At this stage, however, these are not yet drugs: between the identification of an active compound in cell culture and the development of a treatment, many research steps remain necessary.

Beyond its potential applications, Louise Thines’s project touches on a fundamental question in cell biology.

Traditional models have long been used to describe a few major pathways that cells use to internalize molecules on their surface. The discovery and study of clathrin-independent mechanisms now reveal a more diverse landscape. Understanding this diversity provides deeper insight into how a cell continuously regulates its interface with its environment and adapts its behavior.

The MSCA funding enables Louise to continue this exploration, develop new experimental approaches, and strengthen international collaborations. The results are expected, in particular, to help clarify the functioning of this endocytosis pathway and to identify new molecules capable of modulating it.

In fact, I began my research in biology with a doctoral dissertation on hyperoxia—that is, the impact of excess oxygen on cells. At the time, I was working in Professor José Remacle’s lab, where he was studying aging. Aging is characterized by oxidative stress and the formation of free radicals, to which cells can adapt through antioxidant enzymes. To study these, we decided to somewhat exacerbate the situation and create conditions in which oxygen was present in excess. We obtained good results, but this was not a physiological situation. We then turned our attention to the phenomenon of hypoxia-reoxygenation—as occurs during a heart attack—which causes an increase in free radical production during reoxygenation.

We expected to observe changes in the cells during the reoxygenation phase. However, exactly the opposite happened! The majority of the responses occurred during the hypoxia phase—that is, during oxygen deprivation. At the time, this phenomenon had been studied very little. We realized that it triggered a host of effects, particularly in relation to cancer. This research led to a Nobel Prize in 2019.

My research thus led me to become a specialist in how cells respond to various forms of stress. This line of research has also proven extremely fruitful, as we discovered that hypoxia is a major factor in cancer cells’ resistance to various therapies, including chemotherapy. One day, my colleague, physicist Stéphane Vincent, asked me if it was possible to study the cellular response to radiation, particularly proton radiation. More precise than X-ray irradiation, this technique is achieved using a particle accelerator, which UNamur has at its disposal. While this technique was beginning to be used in radiation therapy, the cellular response to it had, however, been studied only to a limited extent.

So-called conventional X-ray radiation therapy lacks precision, which means that healthy tissue surrounding the tumor is also affected by the radiation. To minimize this, we are looking for a way to increase the effects of the radiation within the tumor. This makes it possible to deliver a lower dose of radiation, with fewer side effects on healthy tissue, while maintaining the same therapeutic effect on cancer cells. To achieve this, we use gold nanoparticles, which, due to their unique properties, make tumor cells more sensitive to radiation. However, even though there is still a great deal of enthusiasm surrounding these particles due to the positive results obtained, no treatment has yet been approved by regulatory authorities, which underscores the importance of continuing research.

First and foremost, this is an award recognizing my research as a whole, which is a wonderful scientific acknowledgment of my work. But I want to take this opportunity to emphasize the importance of scientific collaboration, particularly that of physicists Stéphane Lucas and Anne-Catherine Heuskin. Without their contributions, none of this work on radiation therapy would have been possible. We must also acknowledge the importance of Télévie, which has helped fund numerous dissertations on this topic.

This chair also includes a series of five lectures that I will deliver in Mol (province of Antwerp). In addition to the inaugural lecture, which took place in June, these lectures will focus on hypoxia and its effect on resistance to chemotherapy and radiation therapy, the use of nanoparticles as radiosensitizers, and synthetic lethality—a field we have also studied extensively—which involves creating synergy between chemotherapy and radiation therapy. Finally, the last lecture will focus on one of my future areas of research, which concerns immunogenic cell death. The idea is to irradiate cancer cells in such a way that their death activates the immune system against the cancer cells.

This role involves, in particular, managing the funding and organization of research, institutes, and technology platforms through a body known as the Research Council. The Council allocates the various funding sources with the greatest possible transparency. During my two terms in office, I was deeply committed to supporting a diverse range of research topics, in order to provide each with the tools best suited to its needs.

I have also been in close contact with the vice-rectors for research at other French-speaking universities in Belgium. Our goal was to speak with one voice to various stakeholders—from the Walloon Region to the European Union—in order to present a unified set of demands. This was very important to me, and it enabled us to make significant strides, such as securing special funding for technology platforms—which allowed us to acquire state-of-the-art measuring instruments—and establishing an interuniversity platform for alternatives to animal testing.

Why do certain infectious diseases pose a greater risk in some regions than in others? What role do urbanization, climate change, and population movements play in their spread? These are the kinds of questions that interest Catherine Linard, a researcher in the Department of Geography at UNamur. 

A geographer by training, she works in the field of health geography, which studies the relationship between health and place. “I study health, but through the eyes of a geographer. I’m primarily interested in the landscape, and I try to understand the natural and social processes that shape health in a given place.”

Her research focuses specifically on vector-borne diseases—that is, diseases transmitted by organisms such as mosquitoes. These include, in particular, malaria and dengue fever. To better understand their geographic distribution, the researcher analyzes various factors that may influence their transmission. The environment obviously plays a role, since it determines, in particular, where mosquitoes can breed, but it is not enough on its own to explain the spread of a disease. 

 “I take a fairly systemic approach. We’ll look at the environment, but also at human behavior, mobility, and so on.” Part of her research thus focuses on the impact of rapid changes in our environments—such as the rapid urbanization of the African continent—on mosquito-borne diseases. 

 This work has now received significant recognition. Starting in September, Catherine Linard will hold a three-year grant from the Francqui Foundation. Her proposal was first selected by the UNamur Research Council before being approved by the Foundation. 

This appointment will allow the researcher to be relieved of most of her teaching duties so she can devote more time to her research. This is a particularly valuable opportunity given that her daily academic life is divided between teaching, supervising researchers and doctoral students, conducting research, and handling administrative tasks. 

However, there are no plans yet to establish a specific schedule for the next three years. Catherine Linard first wants to take advantage of this newfound availability to devote more time to her ongoing projects and to mentor several doctoral students who are nearing the completion of their dissertations.

The appointment should also enable her to strengthen her international collaborations. In particular, the researcher works with Cheick Anta Diop University in Dakar, Senegal, and plans to use these three years to deepen these exchanges and organize new fieldwork trips. In the longer term, she hopes above all to find time to explore new avenues and determine the future direction of her research. “Research is advancing at a breakneck pace. To stay abreast of everything happening in our field, we need to keep reading and following the work of other teams.” 

Catherine Linard also sees the Francqui Prize as recognition of the work she has carried out with her team and her many collaborators. She also sees it as recognition for the field of health geography, a discipline long overlooked by the general public, but whose importance was particularly highlighted during the COVID-19 pandemic, when understanding the geographic spread of an epidemic became a particularly critical issue. “I believe it is also recognition of the relevance of this research to society, of its ability to shed light on major and highly topical societal issues, as well as of the value of a resolutely interdisciplinary project.” 

Radiotracers are small radioactive molecules used in medical imaging. Once injected into the body, they can bind to specific targets characteristic of a disease and emit radiation that can be detected by imaging devices. Juliette Liégeois, a doctoral student at the Bioorganic Chemistry Laboratory (CBO) at UNamur, is working on these molecules as part of a thesis conducted in collaboration with the company Synlock. “You can compare them to GPS trackers. For example, they make it possible to precisely locate a tumor in the human body and then help the oncologist determine a treatment strategy,” she explains. 

But producing these molecules is a real challenge. Because they are radioactive and unstable, they must be synthesized quickly and under conditions that ensure the safety of the scientists. Their synthesis is therefore carried out using automated machines capable of performing the various steps in sequence without direct human intervention. However, a large portion of the automated systems currently in use still rely on technologies that do not easily accommodate certain newer synthesis methods developed in research laboratories. 

The goal of the SMART project is precisely to bridge this gap by adapting existing methods so they can be integrated into automated systems and to verify their effectiveness under conditions that closely resemble actual production. 

To achieve this, Juliette Liégeois is working on two techniques. Biocatalysis uses enzymes to carry out certain chemical reactions under milder conditions, while photocatalysis uses light to trigger these reactions. These two methods are often used in research but still need to be adapted to the constraints of automated machines. 

The project is also testing the Cheminizer, a technology developed by Synlock. This reactor rotates during the manufacturing process to better mix the various components and more effectively control the reactions. Its operation could, in particular, facilitate the use of light and enzymes.

The SMART project is based on the complementary strengths of UNamur and Synlock. The company contributes its expertise in the design of machinery and reactors, while UNamur’s Bioorganic Chemistry Laboratory (CBO) contributes its knowledge of chemical reactions.