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Flamant, E.

Publications and source records attributed to Flamant, E..

2 recordsLinked to original sources

Genomic adaptation of the picoeukaryote Pelagomonas calceolata to temperate iron-poor oceans revealed by a chromosome-scale genome sequence.

The smallest phytoplankton species are key actors in oceans biogeochemical cycling and their abundance and distribution are affected with global environmental changes. Picoalgae (cells <2{micro}m) of the Pelagophyceae class encompass coastal species causative of harmful algal blooms while others are cosmopolitan and abundant in open ocean ecosystems. Despite the ecological importance of Pelagophytes, only a few genomic references exist limiting our capacity to identify them and study their adaptation mechanisms in a changing environment. Here, we report the complete chromosome-scale assembled genome sequence of Pelagomonas calceolata. We identified unusual large low-GC and gene-rich regions potentially representing centromeres. These particular genomic structures could be explained by the absence of genes from a recombination pathway involving double Holiday Junctions. We identified a large repertoire of genes involved in inorganic nitrogen sensing and uptake and several genes replacing iron-requiring proteins potentially explaining P. calceolata ecological success in oligotrophic waters. Finally, based on this high-quality assembly, we evaluated P. calceolata relative abundance in all oceans using environmental Tara Oceans datasets. Our results suggest that P. calceolata is one of the most abundant eukaryotic species in the oceans with a relative abundance favoured by high temperature and iron-poor conditions. Climate change projections based on its relative abundance suggest an extension of the P. calceolata habitat toward the poles at the end of this century. Collectively, these findings reveal the ecological importance of P. calceolata and lay the foundation for a global scale analysis of the adaptation and acclimation strategies of picoalgae in a changing environment.

genomics↗

A cross-species drug discovery pipeline to identify and validate new treatments for osteosarcoma

PurposeOsteosarcoma is a rare but aggressive bone cancer that occurs primarily in children. Like other rare cancers, treatment advances for osteosarcoma have stagnated, with little improvement in survival for the past several decades. Developing new treatments has been hampered by extensive genomic heterogeneity and limited access to patient samples to study the biology of this complex disease. Experimental designTo overcome these barriers, we combined the power of comparative oncology with patient-derived models of cancer and high-throughput chemical screens in a cross-species drug discovery pipeline. ResultsCoupling in vitro high-throughput drug screens on low-passage and established cell lines with in vivo validation in patient-derived xenografts we identify the proteasome and CRM1 nuclear export pathways as therapeutic sensitivities in osteosarcoma, with dual inhibition of these pathways inducing synergistic cytotoxicity. ConclusionsThese collective efforts provide an experimental framework and set of new tools for osteosarcoma and other rare cancers to identify and study new therapeutic vulnerabilities.

cancer biology↗