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JuryProf. Steve LANNERS (UNamur), ChairProf. Johan WOUTERS (UNamur), SecretaryProf. Pierre FRANCOTTE (ULiège)Dr. Marie HAUFROID (UCB)Prof. Lionel POCHET (UNamur)AbstractCurrently, Mycobacterium tuberculosis remains the second deadliest infectious agent in the world, responsible for 1.6 million deaths in 2021. The burden and cost of current treatment (6 months and 4,000 euros), coupled with the alarming emergence of antibiotic-resistant strains, underscore the absolute urgency of developing new therapeutic molecules. This study focuses on the Mycobacterium tuberculosis phosphoserine phosphatase (MtSerB2), an enzyme essential for serine biosynthesis and vital to the pathogen’s survival. Furthermore, this protein plays a key role in host invasion (through its interactions with the NF-κB factor and the cellular cytoskeleton), making MtSerB2 a prime therapeutic target for the development of new, potent anti-tuberculosis drugs.One of the innovative strategies explored in this thesis is based on destabilizing the protein’s structure (disruption of protein structure). The goal is to design a molecule capable of disrupting the enzyme’s conformation, thereby causing it to lose its catalytic activity. This new class of molecules is expected to exhibit significantly higher selectivity for MtSerB2 compared to its human homolog, human phosphoserine phosphatase (hPSP).To this end, the Mycobacterium avium phosphoserine phosphatase (MaSerB) was initially used as a model system, justified by its 83% sequence identity with MtSerB2 and its propensity to crystallize rapidly. Initially, a virtual screening of drugs already available on the market was conducted to identify potential inhibitors of MaSerB. Enzymatic assays based on malachite green detectionwere then performed to evaluate the inhibitory activity of the various candidates. The results demonstrated increased selectivity of these compounds for dimeric proteins (MtSerB2 and MaSerB) compared to the human enzyme hPSP.Notably, subsequent enzymatic assays conducted directly on MtSerB2 revealed response profiles that differed from those observed with the MaSerB model. To elucidate the molecular basis of these differences, the structure of the protein in its ligand-bound state is currently being investigated. To this end, protein-inhibitor complexes have been crystallized and will be analyzed by X-ray diffraction.

JuryProf. Carine MICHIELS (UNamur), ChairProf. Anne-Catherine HEUSKIN (UNamur), SecretaryProf. Stéphane LUCAS (UNamur)Dr. Rudi LABARBE (IBA)Prof. Joao SECO (German Cancer Research Center)Prof. Simon GALAS (University of Montpellier)AbstractRadiotherapy is one of the most widely used treatments for cancer and plays a central role in modern oncology. While technological advances have greatly improved the precision of radiation delivery, damage to healthy tissues surrounding the tumor remains a major limitation. In recent years, an innovative approach known as FLASH radiotherapy has attracted considerable attention. Unlike conventional radiotherapy, FLASH delivers the therapeutic radiation dose within a fraction of a second using ultra-high dose rates. A growing body of evidence suggests that this approach may reduce radiation-induced side effects in healthy tissues while maintaining the ability to control tumours. However, the biological mechanisms responsible for this protective effect remain poorly understood.This thesis addressed two key challenges in FLASH research. The first was the development and characterization of an experimental platform capable of generating ultra-high dose rate irradiations using the ALTAÏS accelerator at the University of Namur. This work involved designing irradiation systems, validating beam dosimetry, and establishing robust experimental protocols to ensure accurate and reproducible exposure conditions. The second objective was to introduce a new biological model for FLASH investigations: the microscopic nematode Caenorhabditis elegans (C. elegans). This organism offers several advantages, including a short life cycle, ease of handling, low cost, and the conservation of many fundamental biological processes shared with higher organisms. These characteristics make it an attractive complementary model for studying radiation responses and exploring the mechanisms underlying the FLASH effect.This thesis demonstrated the suitability of C. elegans as a model for investigating biological responses to ultra-high dose rate irradiation. Studies of developmental and neurobiological endpoints across multiple irradiation conditions highlighted its potential for mechanistic FLASH research. Together, these findings provide valuable tools to advance our understanding of the FLASH effect. More broadly, they contribute to the development of safer radiotherapy strategies aimed at reducing treatment-related toxicity and improving patient quality of life.

Jointly founded by the University of Namur and UCLouvain, the spin-off Intercept Bio aims to take a new step forward in the prevention of viral respiratory infections. Stemming from research conducted by the teams of Professor Stéphane Vincent at the UNamur Bio-Organic Chemistry Laboratory and Professor David Alsteens at the Louvain Institute of Biomolecular Science and Technology at UCLouvain, and a researcher at the WEL Research Institute, the start-up is developing a nasal spray designed to act right at the entry point for respiratory viruses: the nasal passages.

This is a great recognition of research at UNamur: three Marie Skłodowska-Curie Doctoral Networks (DN) projects have just been awarded, with a key contribution from researchers in Namur! The first, in chemistry, involves Professor Stéphane Vincent; the second, focused on ecosystem resilience, involves Professor Frédérik de Laender; and the third, in the field of photonics, benefits from the expertise of FNRS-qualified researcher Michaël Lobet.