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Biology subjects

Bourgeois, M.

Publications and source records attributed to Bourgeois, M..

5 recordsLinked to original sources

The BPI-like TULIP domain proteins of Drosophila melanogaster: a novel class of candidate odorant transporters.

TULIP (TUbular LIPid binding) domain proteins (TDPs) are found in all living organisms including bacteria. They have various documented functions, some of which clearly related to their intra- or extracellular lipid transfer activities. Extracellular, BPI-related TDPs of insects (B-TDPs, also known as Takeout-related proteins), are often found in chemosensory organs, but little is known regarding their exact location or how they could contribute to olfaction or gustation. We have surveyed and updated the full set of Drosophila B-TDPs and found that roughly 50% are overexpressed in chemosensory organs. Focusing on three genes clustered on the third chromosome, we provide evidence that at least one of the encoded proteins is secreted in the lymph cavity housing the dendrites of olfactory neurons. Biochemical data give support for a putative function of B-TDPs as odorant transporters, but loss-of-function analyses also hint to a potential role as a barrier against plant-emitted terpenoids.

animal behavior and cognition↗

MOSAIC: a longitudinal phenotypic clock to dissect organismal aging trajectories in C. elegans

Interventions that extend lifespan do not necessarily preserve healthspan, the portion of life spent in good health. This disconnect has intensified interest in biological aging clocks as quantitative proxies of organismal health. However, most existing clocks rely on invasive or endpoint measurements, providing static estimates that capture biological age at a single time point and offer limited insight into aging trajectories - the dynamic patterns through which physiological resilience and functional capacity change within individuals over time. Here we combine standardized, high-frequency imaging of individual Caenorhabditis elegans across the lifespan with machine learning to develop MOSAIC (Modular Organismal Signature of Aging In C. elegans), a non-invasive phenotypic clock that estimates biological age longitudinally at single-organism resolution. Leveraging [~]3750 animals, [~]230000 observations and 29 phenotypic features, MOSAIC predicts biological age with high accuracy and resolves organism-wide aging trajectories at high temporal resolution. Beyond age prediction, MOSAIC decomposes biological age into contributions from distinct physiological modules, enabling mechanistic interpretation of organismal decline. Applying MOSAIC to natural lifespan variation, dietary restriction, longevity mutants and pharmacological interventions reveals that lifespan extension can emerge through distinct, time-dependent phenotypic trajectories rather than a uniform slowing of aging. Interventions with similar effects on longevity produce divergent biological-age trajectories and distinct combinations of younger and older traits, highlighting context-dependent physiological trade-offs. MOSAIC provides a scalable, non-invasive framework to repeatedly quantify biological age across the lifespan and to compare interventions based on how they reshape aging trajectories.

bioinformatics↗

Unveiling mode of action of anthelmintics in Caenorhabditis elegans with SydLab™, an on-a-chip automated and high-content screening system.

Anthelmintic resistance in parasitic nematodes presents a growing challenge to animal and human health, driving the need for innovative tools to accelerate drug discovery and mechanistic research. Here, we introduce SydLab, a microfluidic-based, automated phenotypic screening platform that combines continuous imaging, machine vision, and computational analysis for high-content assessment of Caenorhabditis elegans responses to anthelmintics. We systematically evaluated eight anthelmintic compounds spanning major chemical classes-- albendazole, ivermectin, milbemycin oxime, emodepside, levamisole, tribendimidine, monepantel, and closantel--across multiple doses. Using wild-type (N2 Bristol) and mitochondrial stress-sensitive (hsp-6::gfp) strains, SydLab captured real-time, dose-dependent phenotypic profiles over 120 hours, measuring developmental growth, reproduction, motility, and morphology. Emodepside, monepantel, and macrocyclic lactones induced severe larval arrest, reduced worm volume, and distinct morphological changes consistent with neuromuscular paralysis. In contrast, albendazole and closantel showed limited effects at tested concentrations. Machine learning-based shape classification revealed drug-specific morphological signatures, including coiling and cuticular damage, offering insights into compound modes of action. Validation with larval development and migration assays confirmed SydLabs high sensitivity and reproducibility in detecting subtle phenotypic and strain-specific responses. Our study demonstrates how integrating microfluidics, automated imaging, and computational phenotyping enables precise dissection of complex drug-induced effects in nematodes. SydLab provides a scalable, high-throughput platform for anthelmintic screening and mechanistic studies, offering new avenues for antiparasitic drug discovery and resistance research. Author summaryResistance to anthelmintic drugs is a global concern threatening the control of parasitic nematodes that impact human and animal health. New tools are needed to better understand drug effects and accelerate the discovery of effective treatments. In this study, we present SydLab, an automated microfluidic platform that combines real-time imaging and computational analysis to assess the impact of anthelmintic drugs on the model nematode Caenorhabditis elegans. By monitoring development, reproduction, motility, and morphology, we identified unique drug-induced phenotypes linked to specific modes of action. Compounds like emodepside, ivermectin, and monepantel caused larval arrest and neuromuscular paralysis, while albendazole and closantel showed limited activity. Machine learning algorithms detected drug-specific morphological patterns, offering deeper mechanistic insights. Our work highlights SydLab as a powerful high-throughput phenotyping system that can reveal subtle biological responses and support the discovery of next-generation anthelmintics. This approach strengthens our ability to investigate drug resistance and improve therapeutic strategies against parasitic nematodes.

developmental biology↗

Pyruvate carboxylation identifies Glioblastoma Stem-like Cells opening new metabolic strategy to prevent tumor recurrence

Glioblastoma (GBM) are currently associated with a dismal prognosis due to therapeutic resistance. Within the diverse tumor subpopulations, Glioblastoma Stem-like Cells (GSC) have been involved in GBM recurrence. In our study, we demonstrated that these tumor cells can be identified through singular mitochondrial alternative metabolisms. Combining state-of-the-art metabolic studies and the development of a straightforward tumoroid model recapitulating key features of primary GBM cultures, we uncovered a significant use of -ketoglutarate reductive carboxylation and pyruvate carboxylation in tumoroid GBM cells, catalyzed respectively by isocitrate dehydrogenase and pyruvate carboxylase enzymes. We demonstrated that these singular metabolic features are shared by GBM cells from the mesenchymal subtype and radiation-escaping cells, also involved in recurrence. Finally, we demonstrated that pyruvate carboxylation is required for GBM cell survival in hypoxic niches where glutamine is restricted. Thus, besides providing a new way to identify GSC, our study also opens new therapeutic strategy to limit GBM recurrence.

cancer biology↗

Functional cortico-subcortical reorganization after complete hemispheric disconnection for intractable epilepsy

Hemispherotomy is a treatment for drug-resistant epilepsy with the whole hemisphere involved in seizure onset. As recovery mechanisms are still debated, we characterize functional reorganization with multimodal MRI in two children operated on the right hemisphere (RH). We found that interhemispheric functional connectivity was abolished in both patients. The healthy left hemispheres (LH) displayed focal hyperperfusion in motor and limbic areas, and preserved network-level organization. The disconnected RHs were hypoperfused despite sustained network-level organization. Functional connectivity was increased in the left thalamo-cortical loop and between the cerebelli. The classification probability of the RH corresponding to a minimally conscious state was smaller than for the LH. We conclude that after hemispherotomy, neurological rehabilitation is sustained by cortical disinhibition and reinforcement of connectivity driven by subcortical structures in the remaining hemisphere. Our results highlight the effect of vascularization on functional connectivity and raise inquiries about the conscious state of the isolated hemisphere.

neuroscience↗