A5071080367- CRISPR and Genetic Engineering
- Insect symbiosis and bacterial influences
- Single-cell and spatial transcriptomics
- Protist diversity and phylogeny
- Evolution and Genetic Dynamics
- Lipoproteins and Cardiovascular Health
- Plant and animal studies
- Cholesterol and Lipid Metabolism
- Cytomegalovirus and herpesvirus research
- Animal Genetics and Reproduction
- Burkholderia infections and melioidosis
- Molecular Biology Techniques and Applications
- Genomics and Phylogenetic Studies
- Viral Infections and Immunology Research
- Genomics and Rare Diseases
- Legionella and Acanthamoeba research
- Genetic Associations and Epidemiology
- Cell Image Analysis Techniques
- Cancer, Lipids, and Metabolism
- RNA Research and Splicing
- Virus-based gene therapy research
- Pluripotent Stem Cells Research
- Genetics, Bioinformatics, and Biomedical Research
- Advanced biosensing and bioanalysis techniques
Duke University
2022-2025
Duke University Hospital
2024-2025
Duke Medical Center
2024-2025
Applied Genetic Technologies (United States)
2024-2025
Brigham and Women's Hospital
2020-2023
Harvard University
2020-2023
Colby College
2022
In facultative symbioses, only a fraction of hosts are associated with symbionts. Specific host and symbiont pairings may be the result host-symbiont coevolution driven by reciprocal selection or priority effects pertaining to which potential is first. Distinguishing between these possibilities important for understanding evolutionary forces that affect symbioses. We used social amoeba,
Highlights•CRISPR barnyard screens characterize the distribution of ambient gRNAs•CRISPR identify factors influencing abundance gRNAs•CLEANSER is open-source software that assigns gRNAs to cells in perturb-seq screens•CLEANSER demonstrates increased accuracy calling hits published datasetsSummarySingle-cell RNA sequencing CRISPR (perturb-seq) enable high-throughput investigation genome, allowing for characterization thousands genomic perturbations on gene expression. Ambient gRNAs, which are...
The adenosine analogue remdesivir has emerged as a frontline antiviral treatment for SARS-CoV-2, with preliminary evidence that it reduces the duration and severity of illness 1 . Prior clinical studies have identified adverse events 1,2 , been shown to inhibit mitochondrial RNA polymerase in biochemical experiments 7 yet little is known about specific genetic pathways involved cellular metabolism cytotoxicity. Through genome-wide CRISPR-Cas9 screening sequencing, we show leads repression...
Genetic variation contributes greatly to LDL cholesterol (LDL-C) levels and coronary artery disease risk. By combining analysis of rare coding variants from the UK Biobank genome-scale CRISPR-Cas9 knockout activation screening, we substantially improve identification genes whose disruption alters serum LDL-C levels. We identify 21 in which significantly alter at least partially through altered uptake. use co-essentiality-based gene module show that dysfunction RAB10 vesicle transport pathway...
The social amoeba Dictyostelium discoideum is a predatory soil protist frequently used for studying host-pathogen interactions. A subset of D. strains isolated from persistently carry symbiotic
Recent technological developments in single-cell RNA-seq CRISPR screens enable high-throughput investigation of the genome. Through transduction a gRNA library to cell population followed by transcriptomic profiling scRNA-seq, it is possible characterize effects thousands genomic perturbations on global gene expression. A major source noise scRNA-seq are ambient gRNAs, which contaminating gRNAs that likely originate from other cells. If not properly filtered, can result an excess false...
Abstract Interactions between multiple genes or cis-regulatory elements (CREs) underlie a wide range of biological processes in both health and disease. High-throughput screens using dCas9 fused to epigenome editing domains have allowed researchers assess the impact activation repression coding non-coding genomic regions on phenotype interest, but assessment genetic interactions those has been limited pairs. Here, we combine hyper-efficient version Lachnospiraceae bacterium dCas12a...
Genetic variation contributes greatly to LDL cholesterol (LDL-C) levels and coronary artery disease risk. By combining analysis of rare coding variants from the UK Biobank genome-scale CRISPR-Cas9 knockout activation screening, we have substantially improved identification genes whose disruption alters serum LDL-C levels. We identify 21 in which significantly alter at least partially through altered uptake. use co-essentiality-based gene module show that dysfunction RAB10 vesicle transport...
In facultative symbioses, only a fraction of hosts are associated with symbiont. Understanding why specific host and symbiont strains can inform us the evolutionary forces affecting symbioses. Possibilities include ongoing host-symbiont coevolution driven by reciprocal selection, or priority effects that neutral in respect to interaction. We hypothesized would lead higher fitness estimates for naturally co-occurring (native) combinations compared nonnative combinations. used
Abstract The social amoeba Dictyostelium discoideum is a predatory soil protist frequently used for studying host-pathogen interactions. A subset of D. strains isolated from persistently carry symbiotic Paraburkholderia , recently formally described as P. agricolaris, bonniea and hayleyella . three facultative symbiont species present unique opportunity to study naturally occurring symbiosis in laboratory model protist. In addition, there large difference genome size between agricolaris (8.7...
Introduction: Genetic differences in cholesterol metabolism are major contributors to the risk of coronary artery disease (CAD), which is leading cause death USA. Genome-wide association screens have identified over 300 independent genomic loci where genetic variation associated with serum LDL (LDL-C) levels. While several these important drug targets, for vast majority loci, it unknown exact variants, genes and cellular pathways impacted by variants. Hypothesis: We hypothesize that...