Biology subjects

Leroy, G.

Publications and source records attributed to Leroy, G..

3 recordsLinked to original sources

bioRxiv2026

E3 Ligase Ligandalyzer: A Structure-First, Ligand-Centric Platform for E3 Ligase Recruiter Selection

Here, we present E3 Ligase Ligandalyzer Version 1.0, a freely accessible, recruiter-centric web platform for comparative exploration of experimentally resolved E3 ligase-recruiter complexes. The locked Version 1.0 dataset spans 35 E3 ligases, 604 reconciled recruiter entities, and 1,372 active structure-specific recruiter instances across 685 experimentally resolved PDB structures. Recruiters are linked to normalized chemical representations and analyzed using cheminformatics and structure-based workflows to compute physicochemical descriptors, scaffold relationships, aligned binding-pocket views, and solvent-accessible surface area patterns relevant to linker attachment. The platform integrates recruiter-entity, recruiter-instance, scaffold, and ligase views, allowing users to compare experimentally grounded chemical and structural observations without imposing predictive rankings. The platform supports direct transition into downstream degrader-design workflows, including integration with PROTAC Builder (protacbuilder.com). E3 Ligase Ligandalyzer is freely available at https://e3ligandalyzer.com, and the associated code and dataset-generation scripts are available at https://github.com/schurerlab/E3-Ligandalyzer-Scripts.

bioinformatics↗

bioRxiv2023

Reintroducing genetic diversity in populations from cryopreserved material: The case of Abondance, a French local dairy cattle breed

BackgroundGenetic diversity is a necessary condition for populations to evolve under adaptation, selection or both. However, genetic diversity is often threatened, in particular in domestic animal populations where artificial selection, genetic drift and inbreeding are strong. In this context, cryopreserved genetic resources appear as a promising option to reintroduce lost variants and to limit inbreeding. However, while more common in plant breeding, the use of cryopreserved resources is less documented in animals due to a longer generation interval making it difficult to fill the performance gap due to continuous selection. Thus, this study investigates one of the only concrete cases presenting the results of the use of cryopreserved semen of a bull born in 1977 and belonging to a disappeared lineage, into the breeding scheme of a French local dairy cattle breed, the Abondance breed, more than 20 years later. ResultsWe found that this re-used bull was very original relative to the current population and thus allowed to restore genetic diversity lost over time. The expected negative gap in milk production due to continuous selection has been absorbed in a few years by preferential mating with elite cows. Moreover, the re-use of this old bull did not increase the level of inbreeding, it even tended to reduce it by avoiding mating with relatives. Finally, the reintroduction of an old bull in the breeding scheme allowed for increased performance for reproductive abilities, a trait that was less subject to selection in the past. ConclusionsThe use of cryopreserved material was efficient to manage the genetic diversity of an animal population, by mitigating the effects of both inbreeding and strong selection. However, attention should be paid toward mating in order to limit the disadvantages associated with the provision of genetic originality, notably a discrepancy in the breeding values for selected traits or an increase in inbreeding. Therefore, a careful characterization of the genetic resources available in cryobanks could help to ensure the sustainable management of populations and of local or small ones in particular. These results could also be transferred to the conservation of wild populations.

genetics↗

bioRxiv2018

Multiple modes of PRC2 inhibition elicit global chromatin alterations in H3K27M pediatric glioma

A methionine substitution at lysine 27 on histone H3 variants (H3K27M) characterizes ~80% of diffuse intrinsic pontine gliomas (DIPG) and inhibits PRC2 in a dominant negative fashion. Yet, the mechanisms for this inhibition and abnormal epigenomic landscape have not been resolved. Using quantitative proteomics, we discovered that robust PRC2 inhibition requires levels of H3K27M greatly exceeding those of PRC2, seen in DIPG. While PRC2 inhibition requires interaction with H3K27M, we found this interaction on chromatin is transient with PRC2 largely being released from H3K27M. Unexpectedly, inhibition persisted even after PRC2 dissociated from H3K27M-chromatin suggesting a lasting impact on PRC2. Furthermore, allosterically activated PRC2 is particularly sensitive to K27M leading to a failure to spread H3K27me3 at distinct foci. In turn, levels of Polycomb antagonists such as H3K36me2 are elevated suggesting a more global, downstream effect on the epigenome. Together, these findings reveal the conditions required for H3K27M-mediated PRC2 inhibition and reconcile seemingly paradoxical effects of H3K27M on PRC2 recruitment and activity.

molecular biology↗