Biology subjects

Ferrand, M.

Publications and source records attributed to Ferrand, M..

4 recordsLinked to original sources

bioRxiv2022

Interaction between photoperiod and variation in circadian rhythms in tomato

Many biological processes follow circadian rhythmicity and are controlled by the circadian clock. Predictable environmental changes such as seasonal variation in photoperiod can modulate circadian rhythms, allowing organisms to adjust to the time of the year. Modification of circadian clocks is especially relevant in crops to enhance their cultivability in specific regions by changing their sensibility to photoperiod. In tomato, the appearance of mutations in EMPFINDLICHER IM DUNKELROTEN LICHT 1 (EID1, Solyc09g075080) and NIGHT LIGHT-INDUCIBLE AND CLOCK-REGULATED GENE 2 (LNK2, Solyc01g068560) during domestication delayed its circadian rhythms, and allowed its expansion outside its equatorial origin. Here we study how variation in circadian rhythms in tomato affects its perception of photoperiod. To do this, we create near isogenic lines carrying combinations of wild alleles of EID1 and LNK2 and perform transcriptomic profiling under two different photoperiods. We observe that EID1, but not LNK2, has a large effect on the tomato transcriptome and its response to photoperiod. This large effect of EID1 is likely a consequence of the global phase shift elicited by this gene in tomatos circadian rhythms.

plant biology↗

bioRxiv2020

The evolutionary dynamics of genetic incompatibilities introduced by duplicated genes in Arabidopsis thaliana

Although gene duplications provide genetic backup and allow genomic changes under relaxed selection, they may potentially limit gene flow. When different copies of a duplicated gene are pseudo-functionalized in different genotypes, genetic incompatibilities can arise in their hybrid offspring. While such cases have been reported after manual crosses, it remains unclear whether they occur in nature and how they affect natural populations. Here we identified four duplicated-gene based incompatibilities including one previously not reported within an artificial Arabidopsis intercross population. Unexpectedly, however, for each of the genetic incompatibilities we also identified the incompatible alleles in natural populations based on the genomes of 1,135 Arabidopsis accessions published by the 1001 Genomes Project. Using the presence of incompatible allele combinations as phenotypes for GWAS, we mapped genomic regions which included additional gene copies which likely rescue the genetic incompatibility. Reconstructing the geographic origins and evolutionary trajectories of the individual alleles suggested that incompatible alleles frequently co-exist, even in geographically closed regions, and that their effects can be overcome by additional gene copies collectively shaping the evolutionary dynamics of duplicated genes during population history.

evolutionary biology↗

bioRxiv2019

The R2TP chaperone assembles cellular machineries in intestinal CBC stem cells and progenitors

The R2TP chaperone cooperates with HSP90 to integrate newly synthesized proteins into multi-subunit complexes, yet its role in tissue homeostasis is unknown. Here, we generated conditional, inducible knock-out mice for Rpap3 to inactivate this core component of R2TP in the intestinal epithelium. In adult mice, Rpap3 invalidation caused destruction of the small intestinal epithelium, and death within 10 days. Levels of R2TP substrates were decreased, with strong effects on mTOR, ATM and ATR. Rpap3-deficient CBC stem cells and progenitors also failed to import RNA polymerase II in the nucleus. This correlated with p53 activation, cell cycle arrest and apoptosis. Interestingly, post-mitotic, differentiated cells did not display any of those alterations, indicating that R2TP clients are built in actively proliferating cells. Analyses of tissues from colorectal cancer patients revealed that high RPAP3 levels correlate with bad cancer prognosis. Thus, in the intestine, the R2TP chaperone functions in physiologic and pathologic proliferation.

developmental biology↗

bioRxiv2019

Syncytins enable novel possibilities to transduce human or mouse primary B cells and to achieve well-tolerated in vivo gene transfer

Syncytins are cellular transmembrane glycoproteins with fusogenic and immunosuppressive properties that are encoded by endogenous retroviral envelope sequences in mammalian genomes. Based on their properties, syncytins may be useful to pseudotype lentiviral gene transfer vectors (LV) and to obtain well-tolerated in vivo gene delivery but their cellular targets are unknown in this context. We pseudotyped LV with human or murine syncytins. Such LV-Syn particles were infectious in vitro but required a transduction additive, as do other retroviral envelope LV pseudotypes. In these conditions, LV-Syn remarkably transduced quiescent human or murine primary B cells at high level in vitro including naive blood B cells or B cell precursors from murine bone marrow. Transduced human B cells could be expanded in culture and were functional. Human or murine T cells were transduced less efficiently than B cells, in agreement with lower levels of syncytin receptors on T cells compared to B cells. Well-tolerated in vivo gene transfer was possible without additive, as demonstrated with murine syncytin A-mediated gene delivery in C57BL/6 mice. A single intravenous injection of LV-SynA vector to mice led to stable gene transfer into spleen germinal center B cells. LV-SynA were also intrinsically less immunogenic than LV-VSVG, leading to low antibody responses against the vector capsid. This is the first evidence of interactions between syncytins and B cells, providing novel opportunities for B cell genetic engineering and for well-tolerated gene transfer in vivo. The findings also suggest that some immunosuppressive properties of syncytins could be mediated by B cells.\n\nOne Sentence SummarySyncytins are fusogenic cellular proteins that can pseudotype lentiviral gene transfer vector particles, achieving efficient gene transfer into primary quiescent B cells and reducing the in vivo immunogenicity of the particles following systemic administration.

immunology↗