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1,977 results for “CRISPR”
Data from: CRISPR-induced distributed immunity in microbial populations
In bacteria and archaea, viruses are the primary infectious agents, acting as virulent, often deadly pathogens. A form of adaptive immune defense known as CRISPR-Cas enables microbial cells to acquire immunity to viral pathogens by recognizing specific sequences encoded in viral genomes. The unique biology of this system results in evolutionary dynamics of host and viral diversity that cannot be fully explained by the traditional models used to describe microbe-virus coevolutionary dynamics. Here, we show how the CRISPR-mediated adaptive immune response of hosts to invading viruses facilitates the emergence of an evolutionary mode we call distributed immunity - the coexistence of multiple, equally-fit immune alleles among individuals in a microbial population. We use an eco-evolutionary modeling framework to quantify distributed immunity and demonstrate how it emerges and fluctuates in multi-strain communities of hosts and viruses as a consequence of CRISPR-induced coevolution under conditions of low viral mutation and high relative numbers of viral protospacers. We demonstrate that distributed immunity promotes sustained diversity and stability in host communities and decreased viral population density that can lead to viral extinction. We analyze sequence diversity of experimentally coevolving populations of Streptococcus thermophilus and their viruses where CRISPR-Cas is active, and find the rapid emergence of distributed immunity in the host population, demonstrating the importance of this emergent phenomenon in evolving microbial communities.
Data from: Multi-scale model of CRISPR-induced coevolutionary dynamics: diversification at the interface of Lamarck and Darwin
The CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) system is a recently discovered type of adaptive immune defense in bacteria and archaea that functions via directed incorporation of viral and plasmid DNA into host genomes. Here, we introduce a multi-scale model of dynamic coevolution between hosts and viruses in an ecological context that incorporates CRISPR immunity principles. We analyze the model to test whether and how CRISPR immunity induces host and viral diversification and the maintenance of many coexisting strains. We show that hosts and viruses coevolve to form highly diverse communities. We observe the punctuated replacement of extant strains, so that populations have very low similarity compared over the long term. However in the short term, we observe evolutionary dynamics consistent with both incomplete selective sweeps of novel strains and the recurrence of previously rare strains. Coalitions of multiple dominant host strains are predicted to arise because host strains can have nearly identical immune phenotypes mediated by CRISPR defense albeit with different genotypes. We close by discussing how our explicit eco-evolutionary model of CRISPR immunity can help guide efforts to understand the drivers of diversity seen in microbial communities where CRISPR systems are active.
Data from: CRISPR-based herd immunity limits phage epidemics in bacterial populations
Herd immunity, a process in which resistant individuals limit the spread of a pathogen among susceptible hosts has been extensively studied in eukaryotes. Even though bacteria have evolved multiple immune systems against their phage pathogens, herd immunity in bacteria remains unexplored. Here we experimentally demonstrate that herd immunity arises during phage epidemics in structured and unstructured Escherichia coli populations consisting of differing frequencies of susceptible and resistant cells harboring CRISPR immunity. In addition, we develop a mathematical model that quantifies how herd immunity is affected by spatial population structure, bacterial growth rate, and phage replication rate. Using our model we infer a general epidemiological rule describing the relative speed of an epidemic in partially resistant spatially structured populations. Our experimental and theoretical findings indicate that herd immunity may be important in bacterial communities, allowing for stable coexistence of bacteria and their phages and the maintenance of polymorphism in bacterial immunity.
Dataset: CRISPR Therapeutics AG (CRSP) Stock Performance
This dataset provides historical stock market performance data for specific companies. It enables users to analyze and understand the past trends and fluctuations in stock prices over time. This information can be utilized for various purposes such as investment analysis, financial research, and market trend forecasting.
Phenotypically active ORF and CRISPR consensus profiles
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Data from: Is it possible to reconstruct an accurate cell lineage using CRISPR recorders?
Cell lineages provide the framework for understanding how multicellular organisms are built and how cell fates are decided during development. Describing cell lineages in most organisms is challenging, given the number of cells involved; even a fruit fly larva has ~50,000 cells and a small mammal has more than 1 billion cells. Recently, the idea of using CRISPR to induce mutations during development as heritable markers for lineage reconstruction has been proposed and trialled by several groups. While an attractive idea, its practical value depends on the accuracy of the cell lineages that can be generated by this method. Here, we use computer simulations to estimate the performance of this approach under different conditions. Our simulations incorporate empirical data on CRISPR-induced mutation frequencies in Drosophila. We show significant impacts from multiple biological and technical parameters - variable cell division rates, skewed mutational outcomes, target dropouts and different mutation sequencing strategies. Our approach reveals the limitations of recently published CRISPR recorders, and indicates how future implementations can be optimised to produce accurate cell lineages.
Identification of novel HPFH-like mutations by CRISPR base editing that elevate the expression of fetal hemoglobin
<p><span>Naturally occurring point mutations in the <i>HBG</i> promoter switch hemoglobin synthesis from defective adult beta-globin to fetal gamma-globin in sickle cell patients with hereditary persistence of fetal hemoglobin (HPFH) and ameliorate the clinical severity. Inspired by this natural phenomenon, we tiled the highly homologous<i> HBG1</i> and <i>HBG2 </i>proximal promoters using adenine and cytosine base editors that avoid the generation of large deletions. Among the novel regulatory region identified, base editing at -123 region induced HbF to a higher level than disruption of a well-known BCL11A binding site in erythroblasts derived from healthy donor CD34+ HSPC. We further demonstrated <i>in vitro</i> that the introduction of -123T>C and -124T>C HPFH-like mutations drives gamma-globin expression by creating a <i>de novo</i> binding site for the master erythroid regulator KLF1. Overall, our findings shed light on so far unknown regulatory elements within the <i>HBG</i> promoter and identified additional targets for therapeutic upregulation of fetal hemoglobin. </span></p>
Pooled CRISPR Screening of High-content Cellular Phenotypes by Ghost Cytometry_01
<p>Pooled CRISPR screening of high-content cellular phenotypes by ghost cytometry (NFkB NGS data, conventional flow cytometer data, Amnis data)</p>
Pooled CRISPR Screening of High-content Cellular Phenotypes by Ghost Cytometry_02
<p>Pooled CRISPR Screening of High-content Cellular Phenotypes by Ghost Cytometry (Macrophage NGS data)</p>
GeCKO_v2_CRISPR_drug screens in K562 cells
<p>The data contain raw DNA deep sequencing files for GeCKO-v2 genome scale transduced K562 screens with selected drugs (imatinib, dasatinib, asciminib, tivozanib, AZD1775, mepacrine). For all drug except mepacrine the drug, day 0 and day 17 control samples' files are provided. For mepacrine which was screened separately, a triplicate drug, D15 control sample files are provided. The dates are indicated in the file names. </p>
Data from: Costs of CRISPR-Cas mediated resistance in Streptococcus thermophilus
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Data from: CRISPR-induced distributed immunity in microbial populations
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Data from: CRISPR-based herd immunity limits phage epidemics in bacterial populations
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Data from: The effect of bacterial mutation rate on the evolution of CRISPR-Cas adaptive immunity
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Identification of novel HPFH-like mutations by CRISPR base editing that elevate the expression of fetal hemoglobin
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Phage gene expression and host responses lead to infection-dependent costs of CRISPR immunity
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Data from: Multi-scale model of CRISPR-induced coevolutionary dynamics: diversification at the interface of Lamarck and Darwin
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Data from: CRISPR-induced null alleles show that Frost protects Drosophila melanogaster reproduction after cold exposure
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Data from: Is it possible to reconstruct an accurate cell lineage using CRISPR recorders?
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Data from: Dodging silver bullets: good CRISPR gene-drive design is critical for eradicating exotic vertebrates
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