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Biology subjects

Colson, C.

Publications and source records attributed to Colson, C..

5 recordsLinked to original sources

Host-specific adaptation and fitness trade-off of Barley Yellow Dwarf Viruses suggested by experimental evolution through aphid inoculation on multiple Poaceae species

Yellow dwarf viruses are damaging viruses infecting cereals. They are able to infect a wide range of host plants belonging to the Poaceae family. The ban of neonicotinoids in Europe has resulted in an increasing disease incidence and triggered the need to better understand their emergence and spread. The ability of a Barley yellow dwarf virus (BYDV) population to adapt to different hosts has never been studied. We performed an experimental evolution of two BYDV species (BYDV-PAS and BYDV-PAV) to study their adaptation to four Poaceae species (wheat, oat, two-row barley, and six-row barley). After four months of evolution (4 passages from plant to plant), the replicative fitness of the final viral populations was estimated, and the complete viral genomes were sequenced by high-throughput sequencing in pools of BYDV populations. Wildly divergent evolutionary trajectories were obtained, with stable or increased fitness, up to extinctions of viral populations within and among plant species. To understand these results, the composition of viral populations was analysed in detail using single nucleotide polymorphism (SNP) calling, clustering, and haplotype reconstruction methods. Interestingly, adaptation to oat and barley was mainly explained by a combination of BYDV-PAV haplotypes showing specific mutations. In contrast, adaptation to wheat was mainly explained by a combination of BYDV-PAS haplotypes harbouring specific mutations. Moreover, these local adaptations were associated to an adaptation cost in other hosts for some viral populations. The presence of adaptation costs in controlled but realistic conditions opens the door for evaluating practices such as crop mixtures or rotations on fields, as a means to mitigate the impact of BYDV. Author summaryThe use of genetically uniform plant resistant varieties in traditional agriculture creates unique environments that facilitate the rapid emergence of highly virulent pathogen populations. In natural ecosystems, host spatial and temporal heterogeneity help limit the outbreak of epidemics. As a result, disease management strategies such as crop mixtures and rotations have been proposed to reduce the selection pressure exerted on pathogen populations and prevent the emergence of "super-infectious" pathogens. These strategies would be particularly relevant against Barley yellow dwarf virus (BYDV), the virus causing the greatest economic losses on cereals, as insecticides controlling the disease are banned in Europe and few resistance genes are currently available. However, the effectiveness of these strategies against BYDV remains to be demonstrated. By experimentally evolving a natural BYDV population on different cereal species through natural transmission (e.g. vector instead of mechanical inoculation), we showed that different combinations of mutations and haplotypes enable the virus to adapt to different cereal species. Moreover, for some viral populations, the combination promoting adaptation to one host resulted in maladaptation in another host. These host-specific adaptations are key elements in the establishment of crop mixtures and rotations in the field. Our results generated in controlled but realistic conditions demonstrate for the first time that these cultural practices could be effective against these viruses.

evolutionary biology↗

Single cell multi-omic whole genome sequencing and chromatin accessibility profiling reveals genome-epigenome coevolution in colorectal cancer

Epigenetic alterations co-evolve with genetic mutations to drive carcinogenesis and treatment response. Resolving genome-epigenome coevolution requires accurate multi-omic single cell measurement. Here we develop a new technology called "double ATAC" (dATAC) for high-throughput, high-quality, concurrent whole genome sequencing and chromatin accessibility profiling of individual somatic cells. dATAC is a "one pot" method that uses two rounds of tagmentation to sequentially label open chromatin regions and then the whole genome, and produces data of the same quality as current leading single-omic methods. Using colorectal cancer as a model system, we apply dATAC to reveal convergent reorganisation of the epigenome across expanding drug-resistant clones during 5-FU chemotherapy exposure, remarkable stoichiometry of chromatin accessibility at somatic copy number alterations, and the clonal expansion of copy-number altered T cells in the stroma of metastatic disease. dATAC is a robust single cell technology to accurately profile genome-epigenome coevolution across tissues, diseases and species.

molecular biology↗

SLC45A4 encodes a mitochondrial putrescine transporter that promotes GABA de novo synthesis

Solute carriers (SLC) are membrane proteins that facilitate the transportation of ions and metabolites across either the plasma membrane or the membrane of intracellular organelles. With more than 450 human genes annotated as SLCs, many of them are still orphan transporters without known biochemical functions. We developed a metabolomic-transcriptomic association analysis, and we found that the expression of SLC45A4 has a strong positive correlation with the cellular level of {gamma}-aminobutyric acid (GABA). Using mass spectrometry and the stable isotope tracing approach, we demonstrated that SLC45A4 promotes GABA de novo synthesis through the Arginine/Ornithine/Putrescine (AOP) pathway. SLC45A4 functions as a putrescine transporter localized to the peroxisome membrane to facilitate GABA production. Taken together, our results revealed a new biochemical mechanism where SLC45A4 controls GABA production.

biochemistry↗

Evidence that SPIO Chain Formation is Essential for High-Resolution MPI

Magnetic Particle Imaging (MPI) is a noninvasive imaging modality that exploits the saturation properties of superparamagnetic iron oxide particles (SPIOs). A major thrust of MPI research aims to sharpen the magnetic resolution of biocompatible SPIOs, which will be crucial for affordable and safe clinical translation. We recently reported on a new class of MPI tracers --called superferromagnetic iron oxide nanoparticles (SFMIOs) -- which offer much sharper magnetic saturation curves. SFMIOs experimentally demonstrate 10-fold improvement in both resolution and sensitivity. However, superferromagnetism is a relatively unexplored branch of physics and the nanoscale physics and dynamics of SFMIOs remain a mystery. Here we show experimentally that chaining of SPIOs can explain SFMIOs boost in SNR and resolution. We show how concentration, viscosity, transmit amplitude, and pre-polarization time can all affect SPIO chain formation and SFMIO behavior. These experiments will inform strategies on SFMIO chemical synthesis as well as SFMIO data acquisition pulse sequences.

bioengineering↗

First superferromagnetic remanence characterization and scan optimization for super-resolution Magnetic Particle Imaging

Magnetic particle imaging (MPI) is a sensitive, high contrast tracer modality that images superparamagnetic iron oxide nanoparticles (SPIOs), enabling radiation-free theranostic imaging. MPI resolution is currently limited by scanner and particle constraints. Recent tracers have experimentally shown 10x resolution and signal improvements, with dramatically sharper M-H curves. Experiments suggest that this results from interparticle interactions, conforming to literature definitions of superferromagnetism. We thus call our tracers superferromagnetic iron oxide nanoparticles (SFMIOs). While SFMIOs provide excellent signal and resolution, they exhibit hysteresis, with non-negligible remanence and coercivity. We provide the first report on MPI scanning with remanence and coercivity, including the first quantitative measurements of SFMIO remanence decay and reformation using a novel multi-echo pulse sequence. We also describe an SNR-optimized pulse sequence for SFMIOs under human electromagnetic safety limitations. The resolution from SFMIOs could enable clinical MPI with 10x reduced scanner selection fields, reducing hardware costs by up to 100x.

bioengineering↗