Biology subjects

Regnier, L.

Publications and source records attributed to Regnier, L..

3 recordsLinked to original sources

bioRxiv2026

Evolutionary Advantage of Diversity-Generating Retroelements in Switching Environments

Diversity-Generating Retroelements (DGRs) create rapid, targeted variation within specific genomic regions in phages and bacteria. They operate through stochastic retro-transcription of a template region (TR) into a variable region (VR), which typically encodes ligand-binding proteins. Despite their prevalence, the conditions under which maintaining such hypermutating system is favorable remain unclear. Here we introduce a two-timescale framework separating fast VR diversification from slow TR evolution, allowing the dynamics of DGR-controlled loci to be analytically understood. Combining data analysis and analytical calculations we quantity the fitness gain provided by the diversification mechanism of DGR with respect to standard mutagenesis. Our framework accounts for observed patterns of DGR activity in human-gut Bacteroides and clarifies when constitutive DGR activation is evolutionarily favored.

evolutionary biology↗

bioRxiv2025

Polarization MultiFocus Microscopy for volumetric super-resolution and orientation imaging of biofilaments

Accessing molecular orientation in single molecule localization microscopy (SMLM) offers valuable insights into molecular ordering and organization in biological structures. Conventional single-molecule orientation-localization microscopy (SMOLM) methods typically rely on either engineering the microscopes point-spread function (PSF) to encode the orientation information or on polarization resolved detection. While PSF engineering enables detailed orientation analysis, it often requires complex computational analysis and suffers from reduced performance in dense cellular environments due to PSF spreading and overlap. In contrast, polarization-based approaches are easier to implement and are more fit when imaging dense samples but are unable to retrieve the axial information of single molecules. To overcome this limitation, we introduce the Polarization MultiFocus Microscope (PolMFM), a novel method for simultaneously retrieving the orientation and 3D position of single molecules. PolMFM combines the orientation measurement capabilities of a 4-polarization splitting scheme with a 3-planes multifocus microscope (MFM) enabling the reconstruction of molecular 2D orientation, wobble, and axial localization in a single acquisition. Through simulations, we demonstrate that PolMFM accurately recovers both orientation and 3D position, despite PSF defocusing. Experimental validation with reference samples shows that PolMFM matches the orientation precision of 4-Polar STORM, while uniquely adding axial information. We demonstrate the power of PolMFM by resolving the orientation and 3D positions of molecules in actin filaments in fixed cells, and by revealing that chromatin in crickets undergoes major reorganization and increased ordering during spermiogenesis. These findings highlight the potential of PolMFM for high-precision, multidimensional super-resolution imaging in complex and crowded biological environments.

biophysics↗

bioRxiv2023

Chimeric protein EWS-FLI1 drives cell proliferation in Ewing Sarcoma via overexpression of KCNN1.

Ewing sarcoma (ES) is characterized by chimeric fusion proteins, which act as oncogenes. Over the last decade, patient survival has not increased, especially for high risk patients. Knowing that ion channels are studied for their implication in tumorigenesis, the aim of this work is to study the involvement of the SK1 potassium channels in ES. RNA-Seq analyses showed a high restricted expression of KCNN1, the gene encoding SK1, only in ES patients, and its expression is inversely correlated with patient survival. EWS-FLI1 silencing demonstrated the regulation of KCNN1 by these fusion proteins, which bind at GGAA microsatellites near KCNN1 promoter. In addition, KCNN1 has been shown to be involved in the regulation of ES cell proliferation, its silencing being associated with a slowing of the cell cycle. Finally, KCNN1 expression modulates membrane potential and calcium flux suggesting the role of calcium in KCNN1 driving cell proliferation. These results highlight that KCNN1 is a direct EWS-FLI1 and EWS-ERG target, and is involved in the regulation of ES cell proliferation, making it an interesting therapeutic target in ES.

cancer biology↗